TECHNICAL FIELD The present invention relates to novel lysine and lysine-based-diketopiperazine urethanes, ureas, and methods of preparing the same, and their uses.

BACKGROUND ART Polyurethanes and polyurethane ureas (referred as polyurethanes) are the types of polymers that contain urethane (-OCONH-) or urea (-HNCONH-) linkages in the backbone.

Polyurethanes are among the most versatile materials, which have found utility as foams, adhesives, elastomers and plastics. They are present in many of the products we use daily, from household items, sporting goods, and food packaging, to hardwood floors, carpet under layers, wall paints and so on. They are also widely employed as bio-medical and

biodegradable materials. Each year, millions of tons of polyurethanes are consumed worldwide, which in turn raises health and environmental concerns that are associated with polyurethanes and their precursors.

One of the problems is related to toxicity of isocyanate compounds used during the production. Polyurethanes are typically made of diisocyanates, polyols and diamines, where typical diisocyanates include aromatic diisocyanates, e.g., 2, 4-toluene diisocyanate (TDI), 4,4'-diphenylmethane diisocyanate (MDI), and aliphatic diisocyanates, e.g., isophore diisocyanate (IPDI) and hexamethylene diisocyanate (HDI). Although polyurethane products are considered to be non-toxic, diisocyanates are highly reactive and toxic and can cause severe respiratory allergy and other health problems.

Another concern is potential release of hazardous chemicals from polyurethane-based products. (Delilah Lithner, Jeanette Damberg, Goran Dave, Ake Larsson, Chemosphere 74 (2009) 1195-1200). Urethane and urea linkages are known to undergo degradations, e.g., by hydrolysis, thermolysis or microbial ("Chemical degradation of Polyurethane", Vincent Gajewski, Rubber World Sept. 1 , 1990), to give either aromatic diamines that are potentially carcinogenic or aliphatic diamines that, to a less degree, are still toxic. The slow release of toxic amines into the environment, such as 4,4'-diphenylmethanediamine (MDA) from MDI based polyurethane, could pose potential ecotoxicological problems (Maurizio Tosin, Francesco Degli-lnnocenti, and Catia Bastioti, Journal of Environmetal Polymer Degradation (1998), 6(2), 79-90).

Other issues related to polyurethanes include carbon emission and the dependency on petroleum-based raw materials. Due to the tough regulations and pressure to reduce carbon footprints, it is increasingly urgent to produce polyurethanes from renewable natural resources. Natural oil polyols (NOPs), such as castor oil polyols and soybean oil, have been produced and polyurethanes based on NOPs are commercially available now.

Lysine is an amino acid produced from natural resources on a large scale. As an alternative to petrochemical-derived isocyanates, lysine diisocyanate (LDI) derived from lysine has been developed (French Patent 1 ,351 ,368). Early work includes U.S. Patent No. 3,281 ,378 and No. 3,358,005, which disclose the syntheses and usage of polyurethanes, polyureas, and polyurethane ureas obtained from lysine diisocyanate:

OCNCH ₂ CH ₂ CH ₂ CH ₂ CH(COOX)NCO (LDI). Due to its non-toxic degradation nature, for decades, studies have been conducted in the field of synthesis and application of biodegradable polyurethane based on LDI. For example, WO 89/05830 describes biomedical and biodegradable polyurethanes based on lysine diisocyanate, and their potential applications as artificial skins, artificial veins, nerve grafts, etc. U.S. 7,264,823 discloses medical adhesives containing a lysine-isocyanate terminated prepolymer. Rapid degradation of polyurethanes based on LDI and poly(lactic

acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA) polyol has been demonstrated (Z. Wang, L. Yu, M. Ding, H. Tan, J. Li, and Q. Fu, Polym. Chem., 2, 601-607, 2011).

Lysine based polyurethanes disclosed to date are typically made from lysine isocyanate (methyl or ethyl ester). Condensation of lysine ethyl ester and poly-succinimidyl carbonate to give lysine polyurethane is described by Nathan, (A. Nathan, D. Bolikal, N. Vyavahare, S. Zalipsky, and J. Kohn, Macromolecules, 25, 4476-4484, 1992.). In this process,

bis-chlorofomate of polyester reacts first with N-hydroxysuccinimide to yield the

corresponding succinimidyl carbonate derivative, which after purification is then condensed with lysine to give polyurethane.

Being an eco-friendly material, it will be desirable to produce lysine-based polyurethanes directly from cheaper and more readily available lysine and chloroformates by simple and affordable processes.

On the other hand, polyurethanes made from lysine derivatives often have poor solvent and water resistance and poor mechanical properties compared with those made of conventional diamines and diisocyanates (P. C. Caracciolo, F. Buffa, G.A. Abraham, J Mater Sci: Mater Med (2009) 20: 145-155). The drawbacks limit the practical applications of lysine

polyurethane, especially for those where chemical and water resistance, toughness, durability, and cost are the crucial factors for commercial acceptance. It is known in the art of polyurethane that incorporation of segments, for example, crosslinked segments, polymerizable acrylyl moieties (urethane acrylate prepolymer), or copolymerization with acrylate (polyurethane/acrylate/acrylic hybrids-PUA), can improve chemical and water resistance, and other properties. It will be desirable to provide polyurethane hybrids made directly from lysine and its derivatives with improved properties suitable for a wide range of applications,

It is known for decades that amino acids can undergo dimerization to yield cyclic

diketopiperazine compounds:

Amino acids Diketopiperazine

For example, two molecules of lysine are converted into symmetrical

lysine-based-diketopiperazines (S-LDKP) upon heating:

S-LDKP

Unsymmetrical lysine-based-diketopiperazines (U-LDKP) can be obtained by heating lysine and another amino acid:

U-LDKP

Diketopiperazines are naturally-occurring compounds which appear in a variety of natural products, foods and beverages, such as beer (M. Gautschi and J. P. Schmid, J. Agric. Food Chem., 45, 3183-3189, 1997).

Various diketopiperazines have been synthesized and used for drug delivery and other medical purposes (M. del Fresno, D. Fernandez-Forner, M. Miralpeix, V. Segarra, H. Ryder, M. royo and F. Albericio, Bioorganic & Medicinal Chemistry Letters, 15, 1659-1664, 2005; N. Kaur, B. Zhou, F. Breitbeil, K. Hardy, K. S. Kraft, I. Trantcheva, and O. Phanstiel IV, Molecular Pharmaceutics, Vol. 5, No.2, 294-315, 2008; G. Gellerman, E. AZAN, t. Brider, T. Traube, A. Albeck, Int. J. Pept. Res. Ther., 14, 183-192, 2008). Polymeric materials based on diketopiperazines have also been reported. For example, polyamide was obtained by interfacial condensation of lysine-based-diketopiperazines with adipyl chloride (V. Crescenzi, V. Giancotti, and F. Quadrifogilo, Die Makromolekulare Chemie 120 (1968), 220-224). U.S. 3,763,091 describes the reaction of difunctional diketopiperazine, dihydroxyl diketopiperazine and diamino diketopiperazine, with diisocyanates to yield the following polyurethane and urea:

More recently, MDI-terminated polytetramethylene ether glycol (PTMG) and polyethylene ether glycol (PEG) prepolymers have been chain-extended by dihydroxyl diketopiperazine (cyclic dipeptide of L-serine) to yield polyurethane films with interesting biomedical properties. Diketopiperazine-based polymer resins are reported to have good thermal properties with potential application as high-performance materials:

However, diketopiperazine-containing polyurethanes and ureas reported so far are formed by condensation of dihydroxyl diketopiperazine or diamine diketopiperazine with toxic diisocyanates, such as MDI.

Urethanes of lysine-based-diketopiperazines, for example with following structures, are known (M. del Fresno, D. Fernandez-Forner, M. Miralpeix, V. Segarra, H. Ryder, M. royo and F. Albericio, Bioorganic & Medicinal Chemistry Letters, 15, 1659-1664, 2005; N. aur, B. Zhou, F. Breitbeil, K. Hardy, K. S. Kraft, I. Trantcheva, and 0. Phanstiel IV, Molecular Pharmaceutics, Vol. 5, No.2, 294-315, 2008):

However, polymeric urethane made from lysine-based-diketopiperazine with the following structure, in which the nitrogen (N ) atom of the urethane bond is originated from

lysine-based-diketopiperazine has not been reported:

LDKP Urethane linkage

Neither the urea compounds made from lysine-based-diketopiperazines (LDKP-LDKP urea), nor the ureas based on lysine and lysine-based-diketopiperazine (LPKP- Lysine urea) have been reported:

LDKP-LDKP Urea linkage;

LDKP-Lysine Urea linkage;

Therefore, it will be desirable and novel to form the polyurethane structure from

lysine-based-diketopiperazine, in which the nitrogen (W ) atom of the urethane bond is originated from lysine-based-diketopiperazine. It will be also desirable and novel to prepare LDKP-LDKP and LDKP-Lysine urea linkages from lysine-based-diketopiperazine and lysine.

It will be desirable to prepare lysine polyurethanes and ureas from lysine directly by simple and affordable processes.

It will be desirable to prepare lysine and/or LDKP based acrylyl containing urethane prepolymers and lysine and/or LDKP based polyurethane hybrids from lysine and LDKP directly. It will be also desirable to provide low health hazard and eco-friendly, LDKP and/or

LDKP/lysine based polyurethanes suitable for a wide range of commercial applications, such as adhesives, coatings, paints, films, inks, binders, fillers and elastomers for various substrates including woods, metals, plastics, concretes, textiles, glass, fibers, papers, leathers and skins.

DISCLOSURE OF THE INVENTION

The present invention relates to the novel compounds comprising the structural element derived from lysine and lysine-based-diketopiperazines (LDKP): LDKP urethane unit (I), or LDKP-LDKP urea unit (II), or LDKP-Lysine urea unit (III), LDKP-acryl unit (IV), or their repeat units, or their mixtures:

LDKP Urethane(l)

LDKP-LDKP Urea (II)

LDKP-Lysine Urea (III)

LDKP-acryl (IV) The present invention also relates to the methods for preparation of LDKP urethane unit (I), or LDKP-LDKP urea unit (II), or LDKP-Lysine urea unit (III), LDKP-acryl unit (IV), or their repeat units, or their mixtures, and their use.

The present invention also relates to non-isocyanate methods for preparation of lysine polyurethane and urea directly from lysine and its derivatives, and their use:

O LYS HN C O

Lysine Urethane; 0

LYS HN C NH LYS Lysine Urea.

The present invention also relates to non-isocyanate methods for preparation of lysine and/or LDKP based acrylyl containing urethane prepolymers and polyurethane hydrids from lysine and LDKP, and their use.

The invention also relates to methods employing carbonylation agents to produce the aforementioned products. The carbonylation agents are more especially non-isocyanate compounds; particular carbonylation agents include chloro carbonylation agents such as phosgene, diphosgene, triphosgene and bischloroformates; particular bischloroformates are those of formula:

CICO-U-OCCI In which U is a linking group for example alkylene, optionally interrupted by O, and/or optionally substituted. In general U is a group inert to the carbonylation reaction and which thus does not disadvantageously interfere with the carbonylation reaction. The group U may be selected to introduce desired properties in the product. The compounds of the invention may be dimers, oligomers, prepolymers, or polymers including homopolymers and copolymers. The polymers will typically have a Molecular Weight (weight average) greater than 2,000, especially 5,000 to 200,000 and preferably 8,000 to 100,000. Dimers, oligomers and prepolymers will typically have a Molecular Weight (weight average) greater than 300 and preferably 500 to 10,000.

Polyurethane herein may refer to polyurethane, polyurethane urea, a mixture of

polyurethanes, a mixture of polyurethane ureas and a mixture of one or more polyurethanes and one or more polyurethane ureas. DETAILED DESCRIPTION OF THE INVENTION

One aspect of the present invention is the novel compounds comprising the structural element of LDKP urethane unit (I), or LDKP-LDKP urea unit (II), or LDKP-Lysine urea unit (III), LDKP-acryl unit (IV), or their repeat units, or their mixtures: o

-DKP HN- -C 0-

LDKP Urethane (I)

0

- DKP HN- -C NH DKP

LDKP-LDKP Urea (II)

-DKP HN- -C NH LYS

LDKP-Lysine Urea (III)

-DKP-NH-

LDKP-acryl (IV)

in which:

— symbolizes a free valency;

DKP has the structure of: or preferably, n=4 and has the structure of:

and is a segment of symmetrical lysine-based-diketopiperazine (S-LDKP) which has the following structure:

LYS in urea (III) has the following formula: — CH ₂ CH ₂ CH ₂ CH ₂ CH(X)--- and is a segment of lysine derivatives which has the following formula: H ₂ N-CH ₂ CH ₂ CH ₂ CH ₂ CH(X)-NH ₂ where X can be COOH, or COOM (M=metal cation, e.g. Li ⁺ , Na\ K ⁺ , Ca ²⁺ , Zn ²⁺ , and Mg ²⁺ or amine cations, e.g., H ⁺ NR' ₃ , tertiary amine, ammonium, the like and mixtures thereof, or X can be COOR', CONHR', CONR' ₂ , COSR', or the like and mixtures thereof,

R' is a linear or branched, saturated or unsaturated, or cyclic or heterocyclic , substituted or unsubstituted, alkyl radical or aryl radical, or the like and mixtures thereof;

Y can be H, or methyl,

Z is a linking group for example alkylene (e.g., -(CH ₂ ) _m -, m = 2- 0), cyclic alkylene, optionally interrupted by O (e.g., -(CH ₂ CH ₂ 0) ₍ -CH ₂ CH ₂ -, -(CH ₂ CH ₂ CH ₂ CH ₂ 0) _r CH ₂ CH ₂ CH ₂ CH ₂ -, i = 1-20 ), and/or optionally substituted; in which, the compound comprising structure LDKP urethane (I) unit is a macromolecular compound whose molecular weight is larger than 2000, if neither urea (II), nor urea (III), nor unit (IV),

nor — LYS— HNCOO— lysine urethane linkage,

nor — LYS— HNCONH— LYS— lysine urea linkage

is present.

Compound comprising urethane (I) may have the following U-LDKP urethane (I) structure:

U-LDKP Urethane (I) in which n is 1 to 4 and the diketopiperazine is an unsymmetrical

lysine-based-diketopiperazines (U-LDKP) made of lysine and an amino acid other than lysine. Or compound comprising urethane (I) may have the following S-LDKP urethane (I) structure:

S-LDKP Urethane (I) in which diketopiperazine is a symmetrical lysine-based-diketopiperazines (S-LDKP), and both amines of S- LDKP form urethane linkages.

Or compound comprising urethane (I) may have the following S-LDKP urethane (I) structure:

urethane bond

S-LDKP Urethane (I) in which diketopiperazine is a symmetrical lysine-based-diketopiperazines (S-LDKP), and one amine of S-LKDP forms urethane bond and the other amine forms different bond, e.g., amide or urea linkage.

Compound comprising LDKP-LDKP urea (II) may have the following urea structure:

LDKP-LDKP Urea (II) Urea (II) can be di(LDKP) urea, or poly(LDKP) urea, for example, tri(LDKP) tetra(LDKP) urea, in which diketopiperazine (DKP) is a symmetrical

lysine-based-diketopiperazines (S-LDKP) :

O

H

-DKP- -N- -N- -DKP— N- -C- -N- -DKP- H H

Poly(LDKP) urea (II)

Compound comprising LDKP-LYS urea (III) may have the following urea structure:

•

LDKP-Lysine Urea (III) Urea (III) can be LDKP-lysine urea, or poly(LDKP-lysine) urea, for example, LDKP-di(lysine) urea, di(LDKP)-lysine urea, di(LDKP)-di(lysine) urea, tri(LDKP)-lysine urea

tri(LDKP)-di(lysine) urea, or tetra(LDKP)-lysine urea, in which diketopiperazine is a symmetrical lysine-based-diketopiperazines (S-LDKP).

Compound comprising LDKP-acryl unit (IV) may have the following structures in which LDKP is symmetrical:

R =

0 Y

or F* _! is a segment of polyurethane.

Other aspects of the present invention involve the preparation of LDKP urethane unit (I), or LDKP-LDKP urea (II), or LDKP-Lysine urea unit (III), or LDKP-acryl unit (IV), or their repeat units, or their mixtures and the non-isocyanate method of preparation of lysine polyurethane and urea from lysine.

The method for making urethane linkages (I) of this invention comprises reacting

lysine-based-diketopiperazines, for example S- LDKP, preferably its salt, or S-LDKP terminated compound or prepolymer, with a carbonylation agent for example chloroformates, such as bis-chloroformate. Chloroformates can be prepared through phosgenation of the corresponding hydroxyl compounds, e.g., butanediol and polymeric polyol.

O II

CI c o

Lysine polyurethane of this invention is prepared simply by mixing lysine, or its salt, lysine terminated compound or prepolymer, or the mixtures, with chloroformates, such as bis-chloroformate, in the presence of a base, e.g., sodium hydroxide. The method is eco-friendly and affordable, with the advantageous characteristics including short reaction time, low reaction temperature, and most importantly using cheaper and more readily available starting materials.

O

Lysine + CI(CO)0 -» ^{LYS H N C 0}

Reaction may be conducted in a medium, such as in an organic solvent, or aqueous medium, preferably a mixture of water and an organic solvent, in the presence of an acid binding substance, such as sodium carbonate or sodium hydroxide. Optionally, an emulsifying agent may be employed. Reaction may proceed in interfacial form, e.g. emulsion or suspension, or in a solution, at relatively low temperature, e.g., from -20 to 60 °C, preferably 0-30 °C.

Temperature may be raised towards the end of the reaction. The concentration of reaction solution and the ratio of chloroformate to amine may vary depending on the product required. High concentration of reaction solution may give a higher yield of urethane products.

Optionally, chain extenders may be employed.

For example, when bis-chloroformate of butanediol and bis-chloroformate of polyester polyol are used, lysine-based-diketopiperazine polyurethane is synthesized by addition of sodium hydroxide aqueous solution to the mixture of S- LDKP salt aqueous solution and the chloroformates in acetone under vigorous agitation:

CICO-0-(CH ₂ ) ₄ -0-OCCI, + S- LDKP (HCI) + CICO-O-polyester-O-OCCI

-[-CONH-DKP--HN-CO-0-(CH ₂ ) ₄ -0--]--[--CONH-DKP--HN-CO-0--polyester-0--]-

Lysine polyurethane is synthesized by the addition of sodium carbonate aqueous solution to the mixture of lysine methyl ester aqueous solution and bis-chloroformate of

polytetramethylene ether glycol (PT G) in acetone under vigorous agitation:

Lysine (HCI) + CICO-0--PTMG-0-OCCI -[--CONH--LYS--HN-CO-0--PTMG-0--]-

LDKP-LDKP urea (II) and LDKP-lysine urea (III) or lysine-lysine urea linkages, their repeat units, or their mixtures can be prepared by reacting lysine-based-diketopiperazines, for example S- LDKP, preferably its salt, S-LDKP terminated compound or prepolymer, or lysine, lysine terminated compound or prepolymer, or mixtures thereof, with phosgene, diphosgene or triphosgene, or mixtures thereof, in the present of an acid binding agent.

LDKP-LDKP Urea (II)

O

II

CICCI

+ LDKP-LDKP Urea (II) + LYS-LYS Urea LDKP-Lysine Urea (III)

Lysine (HCI) + Phosgene

O

LYS HN— ^ NH LYS

Lysine-Lysine Urea

Reaction may be conducted in a medium, such as in an organic solvent, or aqueous medium, preferably a mixture of water and organic solvent, in the presence of an acid binding substance, such as sodium carbonate or sodium hydroxide. Reaction may proceed in interfacial form, e.g., emulsion, or suspension, or in a solution, at relatively low temperature, e.g., from -20 to 60 °C, preferably 0-30 °C. Temperature may be raised towards the end of the reaction.

For example, in one embodiment, triphosgene in acetone reacts with S-LDKP salts in an aqueous medium by addition of sodium carbonate solution to produce symmetrical LDKP-LDKP urea (II). In another embodiment, triphosgene in acetone reacts with lysine and S-LDKP salts in an aqueous medium by addition of sodium carbonate solution to produce a mixture comprising S-LDKP/S-LDKP urea (II) (mass+H: 539), S-LDKP/LYS urea (III) (mass+H: 429), and other polyureas, for example, S-LDKP/di(LYS) urea (mass+H: 601.4), di(S-LDKP)/LYS urea (Mass+H: 71 1.4), tri(S-LDKP) urea (Mass+H: 821.5),

di(S-LDKP)/di(LYS) urea (mass+H:883.5), tri(S-LDKP)/LYS urea (mass+H: 993.6), tetr a(S-LDKP) urea (mass+H: 1 103.8), tri(S-LDKP)/di(LYS) urea (mass+H: 1 165.8),

tetra(S-LDKP)/LYS urea (mass+H: 1276). Further reaction with bis-chloroformate of polyester polyol gives a S-LDKP/ lysine based polyurethane urea copolymer.

According to the present invention, the reaction may be carried out in different ways in order to obtain desired products, for example, by changing the order of addition of reactants, or adjusting the pH of reaction mixture. Reaction may proceed by adding base to the mixtures of amine salts, chloroformates and/or phosgene; or chloroformates and/or phosgene may be added to the mixtures of amines and base. It is also possible that amines, base,

chloroformates, and/or phosgene are added simultaneously to a reaction medium. The pH of the reaction solution may be adjusted ranging from 4 to 1 , preferably 6-9. Inorganic or organic acid binding substances may be employed, but inorganic base is preferred. Reaction may be conducted in water, or in an organic solvent, but preferably in a mixture of water and organic solvent. The quantity of water and the quantity of organic solvent used during the reaction may vary largely, depending on the type of chloroformates employed and solubility of the product. Soluble solution or dispersion may be formed during the reaction and may be used directly for the application of films, coatings, paints, inks, binders, adhesives, and the like. Gels or precipitant may be produced during the reaction, for example, if reaction is carried out in a concentrated solution.

According to the present invention, it is possible to synthesize the polymers in which, all of the urethane and urea linkages are made of LDKP and lysine derivatives. By selecting proper polyols, such as natural oil polyols, or biodegradable polyols, e.g., castor oil polyols, polycarbonate polyols, or poly(lactic acid) (PLA) based polyols, the present invention teaches the art of the synthesis of low health hazard and environmentally friendly polyurethanes based on renewable materials, LDKP, LDKP/lysine and lysine.

It is known in the art that polyurethanes can be formulated to fit specific applications by selecting appropriate polyols, varying content and distribution of hard segments, adjusting molecular weight or degree of branching or crosslinking. According to the present invention, from the wide selection of polyols and functional compounds, LDKP, LDKP/lysine and lysine based urethane and urea compounds of varied sizes, shapes, and forms may be designed and obtained. They may be small molecules, oligomers, polymers. They may be linear molecules, dendritic compound, branched, hyper-branched, or cross-linked, or they may contain crosslinkable or reactive groups. They may be employed alone, or be part of other compositions, or be blended with others. They may be produced in liquid form, in solution or dispersion, or in solid state form as elastomers, plastics, or binders, fillers, films, pellets, foams, powders, etc. They may comprise additives, such as pigments, coloring agents, UV absorbing agents, stabilizers, anti-oxidants, silicones, flow agents and the like.

Incorporation of segments, such as crosslinked segments, silicon-containing segments, fluorine-containing segments, the like and mixtures thereof, into polyurethane systems are known in the art to improve chemical and water resistance, abrasion, toughness, durability, and other properties. Accordingly, the polymers of the present invention with desired properties may be achieved by incorporating various segments. For example, chloroformate of caster oil has been employed to prepare crosslinked LDKP polyester polyurethane. It is also known in the art that polyurethane/acrylate/acrylic hybrids (PUA) can provide low cost materials with better chemical and water resistance and improved abrasion, toughness, and durability properties. PUAs have been prepared with various methods, e.g., blend, IPN, graft copolymerization, block copolymerization, emulsion or micro-emulsion polymerization.

Accordingly, PUA comprising LDKP urethane unit (I), or LDKP-LDKP urea unit (II) or LDKP-lysine urea unit (III), or LDKP-acryl unit (IV), or lysine urethane, or lysine-lysine urea linkages, their repeated units, or the mixtures can be obtained.

For example, methacrylate-capped S-LDKP urethane (Unit IV: S-LDKP-mono- and double-Hema-capped) and methacrylate-capped lysine urethane (lysine-Hema-urethane) have been prepared by reacting chloroformate of 2-hydroxyethyl methacrylate (HEMA) with S-LDKP and lysine. Further reaction with bis-chloreformates leads to the formation of methacrylate-capped S-LDKP prepolymer (Unit IV: S-LDKP-Hema-urethane prepolymer) and methacrylate-capped lysine urethane prepolymer (Lysine-Hema-urethane-prepolymer). Copolymerization of methacrylate-capped S-LDKP and methacrylate-capped lysine urethane prepolymers with butyl mathacrylate, by UV irradiation, or, heat, or radical initiator, yields crosslinked film (LDKP-Lysine-methacrylate PUA hybrid) with improved water absorption property.

Unit IV: S-LDKP-mono-Hema-capped

Unit IV: S-LDKP-double-Hema-capped

Unit (IV): S-LDKP-Hema-urethane prepolymer

■

Lysine-Hema-urethane prepolymer

LDKP-Lysine-methacrylate PUA hybrid

Other example of unit (IV) includes N-LDKP -(meth)acrylamide

Y=H, methyl

Accordingly, other acrylyl group containing lysine compound and prepolymers, for example, N-lysine-acrylamide and lysine-Hema-ester, may be prepared directly from lysine. Any suitable chloroformate of acrylyl moiety containing polyol, may be employed for the synthesis of PUA of the present invention.

N-lysine-acrylamide

Lysine-Hema-ester

Y = H, methyl It is also known in the art that waterborne polyurethanes (WPU), with considerable environmental friendliness advantages, can be synthesized through the addition of hydrophilic moieties to the polymer chains (US 3,479,310). Prior art provides many examples of waterborne polyurethanes, in which solubility or dispersibility of polyurethanes in water can be improved by attaching anionic groups, such as carboxylic, sulfonic, sulfate, phosphate, or cationic group, such as tertiary amine, or by introducing non-ionic hydrophilic groups, such as polyethoxy chain, repeat unit of ethylene oxide and other alkylene oxides, into polymer chains. Accordingly, the waterborne polyurethanes of the present invention comprising LDKP urethane unit (I), or LDKP-LDKP urea unit (II), or LDKP-lysine urea unit (III), or LDKP-acryl unit (IV), or lysine urethane, or lysine-lysine urea linkages, their repeated units, or the mixtures, can be designed and obtained.

Polyurethane comprising lysine urethane linkage formed directly from lysine can be water soluble or water dispersible. Waterborne urethane copolymers based on S-LDKP, lysine and bis-chloroformates of polyester polyol and butanediol have been achieved through the presence of the carboxylic salt of lysine.

It is known in the art that waterborne polyurethane can be formulated to obtain desired properties. For example, introducing polymerizable acrylyl moieties (urethane acrylate prepolymer), copolymerization with acrylates (PUA hybrids), or incorporation of oils with air-oxidizable, self-crosslinkable ethylenically unsaturated double bonds into polyurethane structures (e.g., fatty acid modified WPU), can improve overall properties of WPU coatings (US 6359060; US 6239209; Z.S. Chen, W.P. Tu, and J.Q. HU; Thermosetting Resin Vol.22, No.2, 51 -54, 2007). Incorporation of silicon- or fluorine-containing segments are another ways of enhancing WPU performance (WO 2006/124035 A1 ; S. H. Park, S. K. Lee, H. Y. Choi, E. M. Lee, E. Y. Kim, C. H. Lim, D. W. Lee and B. K. Kim; Journal of Applied Polymer Science (2009), Vol. 1 1 1 , 1828-1834). Accordingly, the waterborne polyurethane of the present invention comprising LDKP urethane unit (I), or LDKP-LDKP urea unit (II) or LDKP-lysine urea unit (III), or LDKP-acryl unit (IV), or lysine urethane, or lysine-lysine urea linkages, their repeated units, or the mixtures, with special properties may be achieved through crosslinking, grafting, incorporation of special segments and functional groups, such as acrylates, self-crosslinkable ethylenically unsaturated double bonds, epoxy, silicon-containing segments, fluorine-containing segments, or the like. They can be incorporated through any segment of polymers of this invention.

For example, in one embodiment, lysine-hema-PUA prepolymer is obtained by mixing lysine with the chloroformates of hema, caster oil and polyols, and sodium hydroxide solution. The resulting PUA prepolymer can be dissolved in a green organic solvent, e.g., ethanol or isopropanol (alcohol lysine PUA), or be dispersed into water (waterborne lysine PUA), or water/alcohol mixture solvents. Homopolymerization or copolymerization with other monomers, e.g. butyl mathacrylate, by UV irradiation in the presence of photo-initiator yields a crosslinked PUA hybrid with improved water resistance:

— LYS-NH-C-OCH ₂ CH ₂ CH ₃

O

In the practice, amines other than LDKP or lysine may also be employed in order to obtain specific properties. The ratio of components may vary depending upon the physical properties desired in the final polymers.

For example, when isophore diamine (IPDA) is used as the diamine, bis-chloroformate of polyester polyol as a soft segment, lysine as an ionic compound, lysine/IPDA waterborne polyurethane dispersion is synthesized by addition of sodium hydroxide aqueous solution to the mixture of IPDA, lysine and chloroformates in acetone:

IPDA + CICO-0-(CH ₂ ) ₄ -0-OCCI + Lysine (HCI) +CICO-0--polyester~0-OCCI

-[-OCONH-IPDA-HN-CO-0-(CH ₂ ) ₄ -0--]--[--OCONH--LYS--HN-CO-0--polyester-0-]-

Organic layer can be then added into water under strong stirring to give an IPDA-lysine based polyurethane waterborne dispersion after distilling off the acetone. Other polyamines, polyisocyanates and chain extenders may also be employed in the synthesis of lysine and lysine-based-diketopiperazine containing waterborne polyurethane of the present invention. In another example, isophore diamine first reacts with methacrylol chloride to form

N-IPDA-methacrylamide. It is then mixed with bis-chloreformates of polytetramethylene ether glycol (PTMG) and 1 ,4-butanediol, lysine and sodium hydroxide aqueous solution under vigorous agitation to give methacrylamide-IPDA/ lysine urethane prepolymers. The resulting PUA prepolymer can be dissolved in ethanol or isopropanol, or dispersed into water/alcohol mixture solvents. Homopolymerization or copolymerization with other monomers, by UV irradiation, heat, oxidation, or radical initiator, yields a crosslinked PUA.

The present invention provides a simple cost-effective method for preparing polyurethane prepolymer containing polymerizable ethylenically unsaturated group directly from amines, such as lysine and LDKP. Acrylyly moiety is used in the present examples, but other types of polymerizable double bond containing moieties, for example, allyly group may be employed as well. The PUA prepolymer can be used directly from reaction solution for further polymerization, or they can be isolated, and dissolved or dispersed in water, in ethanol or isopropanol, or in water/alcohol mixture for further applications. The hydrophilic group employed in the present examples is the carboxylic acid of lysine. It is obvious that the solubility or dispersibility of the polyurethanes of the present invention in water or

water/alcohol mixtures, or alcohol, can be achieved by attaching anionic groups, such as carboxylic, sulfonic, sulfate, phosphate or cationic group, such as tertiary amine, or by introducing non-ionic hydrophilic groups, such as polyethoxy chain, repeat unit of ethylene oxide and other alkylene oxides, into polymer chains. Any suitable acrylyl compound containing hydrophilic group, such as poly(ethylene glycol) (meth)acrylate,

2-(diethylamino)ethyl (meth)acrylate, 3-sulfopropyl (meth)acrylate (Na ⁺ , K ⁺ ) salt, may be employed in the synthese of the present invention.

The prepolymer of the present invention are capable of homopolymerization and

copolymerization with other monomers or oligomers. From the wide selection of monomers, oligomers and polyols, low-cost lysine based polyurethane hybrids of various structures, compositions and desired properties suitable for different applications may be obtained.

According to the present invention, lysine-based-diketopiperazine may be employed as a salt, such as hydrochloric acid, acetic acid, or sulfate salt, the like, and mixtures thereof. It may be obtained according to various methods. Depending on the preparation process and purity, LDKP may be used as a crude product or aqueous solution, which may contain lysine, polypeptides, amino caprolactam, and other derivatives. Therefore, the resulting urethane and/or urea compounds of the present invention may have peptide and caprolactam segments.

Lysine derivatives may have the following formula:

H ₂ N-CH ₂ CH ₂ CH ₂ CH ₂ CH(X)-NH ₂ (or its salt) wherein X is as defined previously.

Lysine diisocyanates may have the following formula:

OCN-CH ₂ CH ₂ CH ₂ CH ₂ CH(X')-NCO where X' can be COOR', or the like and mixtures thereof,

wherein R is a linear or branched, saturated or unsaturated, cyclo or heterocycio, substituted or unsubstituted, alkyl radical or aryl radical, the like and mixtures thereof. Any suitable chloroformate may be used in the preparation of LDKP, LDKP/lysine and lysine based urethane and/or urea compounds of the present invention. The chloroformates may be prepared in a known manner, such as by the phosgenation of the corresponding hydroxyl containing compound. It is also possible to use crude chloroformates, which may contain hydroxyl group, carbonate linkage, phosgene component, solvent, etc.

Hydroxyl containing compounds used to prepare chloroformates of the present invention may be monohydroxyl compounds, diols, triols, polyols, polymeric polyols, or mixtures thereof. They may contain other substituents, functional groups, unsaturated bonds, hetero elements, such as Si, F, S, N. They may be produced from renewable natural resources and such as to be biodegradable.

Representative examples of hydroxyl containing compounds include, but are not limited to: low molecular weight diols, triols and polyol, including aliphatic, aromatic, mixed aliphatic-aromatic, cycloaliphatic diols, such as ethylene glycol, di- and tri-ethylene glycol, 1 ,2-propanediol, 1 ,3-propanediol, 1 ,3- and 14-butanediol, various pentanediols, hexanediols, heptanediols, octanediols, neopentyl glycol, 2,2-dimethyl propanediol,

3-methyl-1 ,5-pentanediol, 2-ethyl-1 ,3-hexanediol, cyclopentanediols,

di(hydroxymethyl)cyclopentanes, cyclohexanediols, 1 ,4-cyclohexanediol,

di(hydroxymethyl)cyclohexanes, 1 ,4-bis-hydroxylmethyl cyclohexane, thiodiglycols, resorcinol, 4-methyl resorcinol, bisphenyl A, bis(2-hydroxyethyl) bisphenol A,

bis(2-hydroxypropyl) bisphenol A, 4,4'-dihydroxyphenylpropane,

4,4'-dihydroxyphenylmethane, p-xylene glycol, hydroquinone, hydroquinone dihydroxy ethyl ether, glycerol, trimethylolethane trimethylolpropane, butanetriols, pentanetriols, hexanetriols, pentaerythritol, 2-methylglucoside, hexitol, sorbitol, isosorbide, or any other suitable diols, triols and polyols containing or modified with functional groups, e.g., double bond, crosslinkable moiety, the like and mixtures thereof; polymeric polyols, including those typically used in the preparation of polyurethanes, and mixtures thereof, with molecular weight ranging from 300 to 15000, preferably 500 to 5000: any suitable polyether polyols, polyethylene ether glycol (PEG), polypropylene ether glycol (PPG), polytetramethylene ether glycol (PTMG), polyhexylene ether glycol, poly-1 ,2,-dimethyl ethylene ether glycol, polyoxypropylene triol, polyalkylenearylene ether glycols, and any linear and branched polyether polyols or copolymers containing or modified with functional groups, e.g., double bond, crosslinkable moiety, such as poly(ethylene oxide-co-allyl glycidyl ether) polyol, poly(propylene oxide-co-allyl glycidyl ether) polyol, the like and mixtures thereof; any suitable polyester polyols, including those prepared by condensation of diol and polyol, aliphatic, aromatic, mixed aliphatic-aromatic, cycloaliphatic diols, such as ethylene glycol diethylene glycol, propanediols, butanediols, pentanediols, hexanediols, cyclohexanediols, cyclohexanedimethanols, glycerin, 1 ,4-bis-hydroxylmethyl cyclohexane, bis(2-hydroxyethyl) bisphenol A, bis(2-hydroxypropyl) bisphenol A, 4,4'-dihydroxyphenylpropane,

4,4'-dihydroxyphenylmethane, hydroquinone dihydroxy ethyl ether the like and mixtures thereof, with carboxylic acid, such as adipic acid, succinic acid, fumaric acid, malonic acid, oxalic acid, methyl adipic acid, glutaric acid, tartaric acid, citric acid, phthalic acid, maleic acid, thiodipropionic acid, thiodibutyric acid, sulfonyl dibutyric acid, glutamic acid, suberic acid, pimeric acid, sebacic acid, terephthalic acid, isophthalic acid, the like and mixtures thereof, and those prepared by ring opening or other process, such as polyols of

polycaprolactone(PCL), polypropiolactone, polyvalerolactone, polylactide, poly glycolide, their copolymers, and the like; any suitable polycarbonate polyols, such as poly(alkylene carbonate) polyols, polypropylene carbonate) polyol, poly(ethylene carbonate) polyol, poly(butylene carbonate) polyol, poly(hexylene carbonate) polyol, branched poly(alkylene carbonate) polyols,

poly(cycloalkylene carbonate) polyols (e.g., WO Patent 201 1/129940 A1 ), polyether polycarbonate polyols, PACAPOL ^tm , QUICKSTAR ^tm , and those by various suppliers, such as Bayer, Arch Chemicals INC, Daicel Chemical Industries Inc., and any linear and branched polycarbonate polyols or copolymers containing or modified with functional groups, e.g., double bond, crosslinkable moiety, the like and mixtures thereof; any suitable other polymeric polyols, various polyacrylic polyols and polyacetal polyols, hydroxyl-terminated butanediene polymers(HTBP), hydrogenated HTBP, hydroxyl-terminated polysiloxanes, dihydrooxypolydimethylsiloxane, polysulfide polyol, hydroxyl containing polythioethers, hydroxyl-containing epoxies, or any other suitable hydroxyl-containing polymers, copolymers, graft polymers, polymers containing or modified with functional groups, the like, and mixtures thereof; any suitable polyols made from renewable resources, such as natural oil based polyols (NOPs), castor oil polyols, soybean-based polyols, cellulose, or bio-based polyols such as those made by Cargill(BiOH polyols), BASF, HUNTSMAN, BioBased Technologoes,(Agrol), DOW (RENUVA), Bayer, etc., or poly(lactic acid) (PLA)based polyol, such as PLA-PEG-PLA polyol, polyester polyol derived from lactide, or lactic acid and castor oil, or epoxidized fat and oil (e.g., those described in US Patent 2010/0016628 A1 ), lactide/myo-inositol, or any other suitable bio-based polyols, polymers, copolymers, graft polymers, polymers containing or modified with functional groups, the like and mixtures thereof; any suitable copolymer polyol, block copolymer polyol, e.g., PCL-PEG-PCL diol, poly (ester-ether) polyol, polycarbonate ether) polyol, and the like; any suitable hydroxyl compound or polyol containing oxidizable, self-crosslinkable ethylenically unsaturated double bond, such as unsaturated fatty acid polyols, (e.g., those described in US 2008/0236449A1 , US 2006/0089453A1 , US 6.620.893B1 , US 6,359,060B1 ,US 6,239,209B1 ); any suitable hydroxyl compound or polyol containing polymerizable unsaturated double bond acrylate or methacrylate compound (referred as (meth)acrylate), such as 2-hydroxyethyl (meth)acrylate, (2 or 3)-hydroxypropyl (meth)acrylate, 4-hydroxylbutyl (meth)acrylate, glyceryl (meth)acrylate, ACE ^tm hydroxyl acrylate monomer, the like and mixtures thereof; other hydroxyl containing compounds, such as vinyl alcohol, fluoroalkyl alcohols, zonyl, polyols containing pendent fluoroalkyl groups, and the like.

Any suitable (alkyl)acrylate, acrylate, methacrylate, acrylic, acrylamide or vinyl monomers can be employed for the preparation of PUA hybrids, waterborne PUA hybrids and alcohol PUA hybrids of the present invention. Examples include, but are not limited to, methyl methacrylate, methyl acrylate, ethyl methacrylate, ethyl acrylate, (n-, t-)butyl (meth)crylate, hexyl

(meth)acrylate, cyclohexyl acrylate, methacrylic acid, acrylic acid, ethylene glycol methyl ether (meth)acrylate, di(ethylene glycol) ethyl ether (meth)acrylate, poly(ethylene glycol) ethyl ether (meth)acrylate, ethylene glycol di(meth)acrylate, di(ethylene glycol) di(meth)acrylate, tri(ethylene glycol) di(meth)acrylate, tetra(ethylene glycol) di(meth)acrylate, poly(ethylene glycol) di(meth)acrylate, glycerol di(meth)acrylate mixture isomers, tri(ethylene glycol) methyl ether (meth)acrylate, 1 ,4-butanediol di(meth)acrylate, 1 ,6-hexanediol diacrylate, polyethylene glycol diacrylate, polyester acrylate, polycarbonate acrylate, dially carbonate, diallyl ether, fluoroalkyl (meth)acrylate, such as perfluorooctylethyl acrylate, hexafluorobutyl acrylate, 2,2,2-trifluoroethyl (meth)acrylate, 1 H,1 H,2H,2H,-perfluorodecylacrylate,

1 H, 1 H,-perfluorooctyl (meth)acrylate, Zony TM fluoro monomer, glycidyl (meth)acrylate, soybean oil expoxidized acrylate, 2-(diethylamino) ethyl (meth)acrylate, 2-(dimethylamino) ethyl (meth)acrylate, 3-(dimethylamino) pro[yl arcylate, N-[3-(dimethylamino) propyl] methacryamide, 3-sulfopropyl (meth)acrylate (Na ⁺ , ⁺ ) salt, and those described in US 4,241 ,202, US 4,250,322, US 5,512,205, DE 2365631 , JP 277308. Chloroformates of acrylyly or methacrylyl moiety containing polyols may also be used. Monomers, oligmors and crosslinkers containing multiple and/or different polymerizable unsaturated groups, such as those disclosed and mentioned in US 5,512,205 (acrylyl-, vinyl-, styrene-, or the

mixture-containing monomers or crosslinkers). Various known polymerization initiators, such as azoisobutylnitrile (AIBN), benzoylperoxide, potassium persulfate, photo initiators, e.g., those of Irgacure from Siba, and the like may be employed. Any suitable compound, which may contain anionic groups, such as carboxylic, sulfonic, sulfate, phosphate, or cationic group, such as tertiary amine, or non-ionic hydrophilic groups, such as polyethoxy chain, repeat unit of ethylene oxide and other alkylene oxides, e.g., polyethoxy diol, poly(ethoxy/-propoxy) diol, a diol containing a pendant ethoxy chain, etc., may be employed in the syntheses of waterborne or alcohol polyurethane of the present invention.

Any suitable chain extender may be used in the preparation of urethane and/or urea compounds of the present invention. They can be selected from, but are not limited to, polyisocyanates, polyamines, polychloroformates, phosgene, diphosgene, triphosgene, the like, and mixtures thereof.

Any suitable acid binding agent, organic base, e.g., tertiary amine, or inorganic base, such as hydroxide, oxide, carbonate, hydrogen carbonates of the alkali metals and alkaline earth metals, or the mixtures, may be used in the preparation of urethane and/or urea compounds of the present invention. Examples include, but are not limited to, sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate, calcium hydroxide, ammonia, ammonium hydroxide, and the like.

Excess of reactant amines, such as lysine-based-diketopiperazine, or lysine, may also act as acid scavengers. Any suitable amines may be employed in the preparation of urethane and /or urea compounds of the present invention. Amines can be primary or secondary aliphatic, alicyclic, aromatic or heterocyclic polyamines, polymeric amines, or any suitable amine, their derivatives or mixtures. Representatives include, but are not limited to, ethylene diamine, propylene diamine, tetramethylene diamine, pentamethylene diamine, hexamethylene diamine, heptamethylene diamine, octamethylene diamine, piperazine, 2,5-dimethylpiperazine, (m-.p-)xylene diamine, 1 ,4-diaminocyclohexane, p-phenylene diamine,

1 ,5-naphthylenediamine, isophore diamine, 4,4'-diphenylmethanediamine,

bis(p-aminocyclohexyl)methane, 1 ,3-di(4-piperidinyl)propane, amino containing or terminated polymers such as Jeffamines, various sulfonic acid diamines such as (2,4- or 2,5-) diaminobenzene sulfonic acid, (2,5- or 2,6-)diaminotoluene-4-sulphonioc acid, hydrazine, and many more. Triamines or tetramines or polyamines or derivatives of the said amines or mixtures of the said amines may also be used. In the practice of the present invention, polyisocyanates may also be employed.

Polyisocyanates may react with amines or hydroxyl groups, LDKP, LDKP-terminated prepolymer, lysine, lysine-terminated prepolymer, or be used as chain extenders. Isocyanates can be primary or secondary aliphatic, alicyclic, aromatic or heterocyclic polyisocyanates, or isocyanate-terminated prepolymers, or any suitable isocyanate, or their derivatives or mixtures. Representatives include, but are not limited to, isophore diisocyanate (IPDI), hexamethylene diisocyanate(HDI), methylene bis (p-cyclohexl) isocyanate(H12MDI), cyclohexyl diisocyanate(CHDI), 2, 4-toluene diisocyanate (TDI), 4,4'-diphenylmethane diisocyanate (MDI), p-phenylene diisocyanate(PPDI), 1 ,5-naphthylene diisocyanate, tolidine diisocyanate, (m-.p-)xylene diisocyanate, and more. Triisocyanates, such as lysine based triisocyanate, or tetraisocyanates or polyisocyanates or derivatives of the said isocyanates or mixtures of the said isocyanates may also be used.

Any suitable solvent or diluent may be used in the preparation of urethane and/or urea compounds of the present invention. It can be water, or organic solvent, preferably a mixture of water and organic solvent. It can be water miscible or immiscible, such as acetone, methyl ethyl ketone, tetrahydrofuran, methanol, ethanol, isopropanol, dioxane, ethyl acetate, acetonitrile, diethyl ether, aromatic hydrocarbon such as toluene, chlorinated aromatic or aliphatic hydrocarbons and the like. Mixtures of such solvents may also be used. LDKP urethanes of the present invention may be obtained by routes other than by the reaction of LDKP with chloroformates. For example, reaction of LDKP with carbonates, such as dimethyl carbonate or cyclic carbonates, may lead to the formation of urethanes of the present invention. It is also possible that chlorofomate first reacts with N-hydroxysuccinimide to yield the corresponding succinimidyl carbonate derivative, which is then condensed with lysine diketopiperazine to give diketopiperazine urethane. LDKP-Lysine urea (III) may also be obtained by reaction of LDKP with lysine diisocyanate derivatives.

The present invention provides a simple non-isocyanate method to produce LDKP,

LDKP/lysine and lysine based urethane and urea compounds from LDKP, lysine and its derivatives. According to the method of the present invention, it will be apparent to those skilled in the art that a wide variety of combinations are possible to yield various LDKP and lysine products and copolymers according to the ultimate use without departing from the spirit of the invention.

Lysine polyurethanes are known in the art to be used as biomedical and biodegradable materials. They have been tailored to fit various usages, such as adhesives, artificial skins, wound dressings, artificial veins, gels, etc. The present invention provides an alternative low-cost green method for the preparation of lysine urethane and urea compounds directly from more readily available lysine, instead of lysine diisocyanate. Therefore, they may have similar applications as those of lysine polyurethane prepared via the known conventional isocyanate process.

According to the present invention, the novel LDKP and LDKP/lysine based urethane and urea polymers of the present invention provide the alternative polyurethanes of comparable performance based on raw materials deriving from natural renewable resources. They are intended to replace polyurethanes made of conventional isocyanates and may have as many applications as those of conventional polyurethanes, providing the advantages of the absence of health and environmental hazard. They may be utilized in preparing various polyurethane articles, such as coatings, paints, adhesives, inks, binders, fillers, castings, elastomers, fibers, gels and the like in the art, for packaging, toy, cosmetic, building materials, automobiles, biomedical, and other urethane related industries.

It has been found that LDKP polyurethanes of the present invention exhibit excellent film-forming property and moisture resistance. For example, the coating of LDKP

polyurethane made from polyester and castor oil polyols has less than 4% water uptake and displays a good resistance to scratch. The thermal stability of LDKP polyurethane of the present invention has been found to be eminently higher (e.g., 5% weight loss at 310 °C) than that of lysine polyurethane (<260 °C). LDKP/lysine based PUA copolymer (urethane/acrylate hybrids) displays an excellent water resistance. With the combination of proper polyols, functional groups and additives, it is possible to formulate LDKP and LDKP/lysine based polyurethane films, coatings and paints of varied properties, suitable for a range of high performance applications on various substrates including woods, metals, plastics, concretes, textiles, glass, fibers, papers, leathers, artificial leathers, and skins. LDKP , LDKP/lysine and lysine polyurethanes of the present invention may be used as adhesives for laminates, flexible packaging, multilayer films, leathers and artificial leathers, shoes, printing inks and other adhesive related applications. LDKP, LDKP/lysine and lysine polyurethanes with various soft or melting points can be obtained. They display excellent hot-melt adhesive properties on surfaces such as glass, metals, woods, and papers. LDKP, LDKP/lysine and lysine polyurethanes of the present invention may be especially useful as adhesives for food package, flexible package, medical package, e.g., glues for papers, labels, or glues for caps and closures of containers, bags, bottles, where adhesives may come in contact with the food products, medicines etc. They may also be useful as adhesives for plywood and furniture, providing good properties normally associated with polyurethane adhesives without releasing toxic chemicals such as formaldehyde fumes or diamines.

LDKP, LDKP/lysine and lysine polyurethanes of the present invention may be useful in preparing moldings, or casting articles of various kinds, and the like, such as toys, sporting goods, household items.

LDKP, LDKP/lysine and lysine polyurethanes of the present invention may be useful as biomedical materials for making various biomedical products and applications, such as artificial skin, wound dressings, artificial veins, medical devices, bandages, pads, tubings, gels, drug delivery, etc. They may be excellent biodegradable materials, especially when biodegradable polyols such as polycarbonate or PLA polyols are employed.

LDKP , LDKP/lysine and lysine based waterborne polyurethanes (WPU), waterborne or alcohol urethane-acryl prepolymers and PUA hybrids, have the advantages including environmental friendliness, low cost and good water resistance. They may be utilized in preparing various polyurethane articles, such as coatings, paints, adhesives, inks, binders, castings, gels and the like in the art, Coatings, paints, adhesives, or films may be obtained from LDKP, LDKP/lysine and lysine polyurethanes of the present invention by any suitable known method, including spray, brush, roller coating, casting, dipping, or hot-melt.

The following embodiments and examples will provide better understanding of the present invention. However, it will be understood, by those skilled in the art, that a wide variety of combinations may be employed to yield products which may be varied widely in structures and properties according to the ultimate use without departing from the basic concept and spirit of the invention.

Examples Example 1

1 gram of bis-chlorformate of polyester polyol, (phosgenation product of polyester polyol, Mn = 2000, made of hexanedioic acid, 1 , 4-butanediol and 1 , 2-ethanediol), and 0.15 gram of bis-chlorformate of 1 , 4-butanediol are dissolved in 10 ml of acetone cooled by ice water. To this are added with agitation a solution of 0.48 gram of symmetrical

lysine-based-diketopiperazines dihydrochoride in 1 ml of water, a solution of 0.24 gram of sodium hydroxide in 1 ml of water, and then 30 mg of triphosgene. The temperature of reaction mixture is maintained around 5-15 ⁰ C during the addition. After further stirring at room temperature, the polymer is removed, washed with water and dried. The resultant S-LDKP polyurethane displays excellent hot-melt adhesive properties on surface of glass and paper. The film coat of the obtained polymer has a water absorption of 6 % and hardness of F-H. Example 2

1.16 grams of bis-chlorformate of polytetramethylene ether glycol (PTMG, Mn = 1000), is dissolved in 15 ml of acetone cooled by ice water. To this is added with agitation a solution of 0.33 gram of lysine methyl ester dihydrochoride in 1 ml of water, followed by a solution of 0.49 gram of sodium carbonate in 2 ml of water while the temperature is held around 5-15 ⁰ C during the addition. It is then allowed to stir at room temperature until solution becomes viscous and pH is adjusted to 7. Polyurethane obtained is removed, washed with water and dried. The film coat of resultant polyurethane has a water absorption of 60.4 % and displays an excellent adhesive property on surface of glass, wood, metal and paper. Example 3

0.52 gram of symmetrical lysine-based-diketopiperazines dihydrochoride is dissolved in 15 ml of water cooled by ice water. To this are added with agitation a solution of 0.30 gram of sodium carbonate in 2 ml of water and a solution of 0.03 gram of triphosgene in 2 ml of acetone. The reaction mixture is stirred for 20 min at 10-15 ° C and then pH is adjusted to 6 with dilute hydrochloric acid aqueous solution. After removal of the solvents, the residue gives the mixtures of lysine-based-diketopiperazines ( S-LDKP, Mass+H: 257) and S-LDKP/S-LDKP urea (II) (Mass+H: 539). Example 4

0.2 gram of symmetrical lysine-based-diketopiperazines dihydrochoride and 0.2 gram of lysine monohydrochoride are dissolved in 5 ml of water cooled by ice water. To this are added with agitation a solution of 0.16 gram of sodium carbonate in 1 ml of water and a solution of 0.04 gram of triphosgene in 1 ml of acetone. The reaction mixture is stirred for 20 min at 10-15 ° C and then pH is adjusted to 6 with dilute hydrochloric acid aqueous solution. After removal of the solvents, the residue gives the mixtures : S-LDKP/S-LDKP urea (II) (Mass+H: 539), S-LDKP/LYS urea (III) (Mass+H: 429) and polyureas, e.g., S-LDKP/di(LYS) urea (mass+H: 601.4), di(S-LDKP)/LYS urea (Mass+H: 71 1.4), tri(S-LDKP) urea (Mass+H: 821.5), di(S-LDKP)/di(LYS) urea (mass+H:883.5), tri(S-LDKP)/LYS urea (mass+H: 993.6), tetra(S-LDKP) urea (mass+H: 1 103.8), tri(S-LDKP)/di(LYS) urea (mass+H: 1 165.8), tetra(S-LDKP)/LYS urea (mass+H: 1276).

Example 5

0.33 gram of symmetrical lysine-based-diketopiperazines dihydrochoride and 0.23 gram of lysine monohydrochoride are dissolved in 1 ml of water cooled by ice water. To this are added with agitation a solution of 0.10 gram of sodium carbonate in 0.5 ml of water and a solution of 0.015 gram of triphosgene in 1 ml of acetone. The reaction solution is stirred at 5-15 ° C and then mixed with 3.5 grams of bis-chlorformate of polyester polyol (phosgenation product of polyester polyol, Mn = 2000, made of hexanedioic acid, , 4-butanediol and 1 , 2-ethanediol) in 0 ml of acetone. To this is added with agitation a solution of 0.70 gram of sodium carbonate in 2 ml of water while the temperature is held around 5-15 ° C and pH is around 6-8 during the addition. It is then allowed to stir at room temperature until solution becomes viscous.

Polyurethane urea obtained is removed, washed with water and dried. Example 6

4.9 grams of bis-chlorformate of polyester polyol (phosgenation product of polyester polyol, Mn = 2000, made of hexanedioic acid, 1 , 4-butanediol and 1 , 2-ethanediol), 0.92 gram of bis-chlorformate of 1 ,4 -butanediol and 1.0 gram of chloroformate of caster oil are dissolved in 20ml of acetone cooled by ice water. To this are added with agitation a solution of 3.2 grams of symmetrical lysine-based-diketopiperazines dihydrochoride in 3 ml of water and a solution of 1.4 grams of sodium hydroxide in 2 ml of water while the temperature is held around 5-15 ° C during the addition. It is then allowed to stir at room temperature until solution becomes viscous. The resultant polymer is removed, washed with water and dried. The film coat of the obtained polyurethane has a water absorption of 4 %, hardness of F-H and displays a good resistance to scratch.

Example 7

0.13 gram of chloroformate of 2-hydroxyethyl methacrylate (HEMA) is dissolved in 1 ml of acetone cooled by ice water. To this are added with agitation a solution of 0.3 grams of symmetrical lysine-based-diketopiperazines dihydrochoride in 2 ml of water and a solution of 0.12 gram of sodium carbonate in 1 ml of water while the temperature is held around 5-15 ° C. The reaction mixture is then allowed to stir at room temperature and pH is adjusted to 6 with dilute hydrochloric acid aqueous solution. After removal of the solvents, the residue gives the mixtures containing mainly S-LDKP-mono-Hema urethane (IV) (Mass+H: 413), and a small amount of HEMA-S-LDKP-double-Hema urethane (Mass+H: 569).

Example 8

0.31 gram of chloroformate of 2-hydroxyethyl methacrylate (HEMA) is stirred in 3 ml of THF cooled with ice water. To this is added with agitation 1 ml of aqueous solution containing about 0.25gram of symmetrical lysine-based-diketopiperazines dihydrochoride and 0.25 gram of lysine hydrochloride, followed by the addition of sodium hydroxide solution dropwise. Then, the mixture of .12 grams of bis-chlorformate of polytetramethylene ether glycol (PTMG, Mn = 1000) and 0.12 gram of bis-chlorformate of 1 ,4-butanediol in 8 ml of cold THF is added, followed by the addition of sodium hydroxide solution dropwise. During the addition, the temperature of reaction mixture is maintained around 5-15 ° C and the pH is around 4-9. After stirring 1 hour at room temperature, organic layer is separated from aqueous solution and 0.5 gram of butyl mathacyrlate and 0.06 gram of photo-initiator, Irgacure 2959(Siba) are added. Irradiation (NOVACURE, 100 W Hg vapor short arc) of the coat of the obtained

urethane-acrylate solution yields a tough film with a water absorption of 3%.

Example 9

grams of lysine hydrochloride is dissolved in 2 ml of water cooled by ice water. To this are added with agitation a solution of 1.1 grams of chloroformate of 2-hydroxyethyl methacrylate (HE A) in 2 ml of cold acetone and sodium hydroxide solution. The temperature of reaction solution is held around 5-15 ° C and pH is around 6-8. Then, the mixture of 1.0 gram of bis-chlorformate of polytetramethylene ether glycol (PT G, Mn = 1000), 0.12 gram of bis-chlorformate of 1 ,4-butanediol and 0.03 gram of chloroformate of castor oil in 8ml of cold acetone is added, followed by the addition of sodium hydroxide solution drop wise. The temperature of the mixture is held around 5-15 ° C and pH is around 6-9 during the addition. After further agitation, the solution is adjusted to pH around 7. To this is added with 0.08 gram of photo-initiator, Irgacure 2959( Siba). The obtained solution is divided into two parts. Part one is subjected to a strong agitation to give a lysine-urethane-methacrylate prepolymer waterborne dispersion after distilling off the acetone. Irradiation (NOVACURE, 00 W Hg vapor short arc) of the coat of lysine-urethane-methacrylate prepolymer waterborne dispersion yields a crosslinked film with a water absorption large than 80 %. Part two, after removing solvent, yields the sticky lysine PUA prepolymer which is then dissolved in a water/alcohol mixture solvents to give an alcohol PUA prepolymer solution. Copolymerization with butyl mathacrylate, by UV irradiation the coat of mixtures in the presence of

photo-initiator, yields a crosslinked PUA hybrid with a water absoption of 25 %.

Example 10

2.1 grams of bis-chlorformate of polyester polyol (phosgenation product of polyester polyol, Mn = 2000, made of hexanedioic acid, 1 , 4-butanediol and 1 , 2-ethanediol) and 0.4 gram of bis-chlorformate of ,4-butanediol are dissolved in 20 ml of acetone cooled by ice water. To this are added dropwise with agitation a solution of 0.18 gram of IPDA in 1 ml acetone and a solution of 0.45 gram of lysine hydrochloride in 1.5 ml of water, followed by a solution of 0.3 gram of sodium hydroxide in 2 ml of water. The temperature of reaction solution is held around 5-15 ° C and pH is controlled around 6-8 during the addition. It is then allowed to stir at room temperature until solution becomes viscous. Organic layer is then added into water under strong stirring to give an IPDA-Lysine based polyurethane waterborne dispersion after distilling off the acetone. The film coat of resultant waterborne polyurethane displays an excellent adhesive property on paper.

Example 11

0.2 gram of methacrylol chloride in 1 ml of cold THF is added with agitation to a solution of 0.34 grams of isophore diamine in 10 ml of THF cooled by ice water. To this are added 0.26 gram of lysine hydrochloride in 2 ml of water, 1.0 gram of bis-chlorformate of polytetramethylene ether glycol (PT G, Mn = 1000) and 0.3 gram of bis-chlorformate of 1 ,4-butanediol in 5 ml of THF, followed by sodium hydroxide solution dropwise. The temperature of reaction solution is held around 5-15 ° C and pH is around 7-9. After further agitation at room temperature, the organic layer is separated to give the sticky PUA prepolymer after distilling off the solvent. The resulting PUA prepolymer is soluble in ethanol and isopropanol, and can be dispersed into water/ethanol (2:1 ) mixture solvents.

Copolymerization with butyl mathacrylate, by UV irradiation of the coat of the mixtures in the presence of Irgacure 2959( Siba), yields a crosslinked tough PUA film. Example 12

2.23 grams of bis-chlorformate of polytetramethylene ether glycol (PTMG, Mn = 1000) is added with strong agitation into 20 ml of aqueous solution containing 0.49 gram of lysine hydrochloride cooled by ice water. To this is added sodium hydroxide aqueous solution (about 0.3 gram in 3 ml of water) slowly so that the pH of the reaction mixture is maintained around 7-9 and the temperature is kept around 10-20 ° C during the addition. The solution is then allowed to stir at room temperature overnight. The film of resultant polyurethane displays a good elastic property.

Example 13

1.08 grams of bis-chlorformate of polytetramethylene ether glycol (PTMG, Mn = 1000), and 0.1 1 gram of bischlorformate of 1 ,4-butanediol are dissolved in 10 ml of acetone cooled by ice water. To this are added with agitation 1 ml of aqueous solution containing about 0.24 gram of symmetrical lysine-based-diketopiperazines dihydrochoride and 0.24 gram of lysine hydrochloride, followed by the addition of 0.24 gram of sodium hydroxide in 1 ml of water dropwise. The temperature of reaction mixture is maintained around 5-15 ° C and the pH is around 6-8 during the addition. After the solution becomes very viscous, polymer is removed, washed with water and dried. The resultant polyurethane melts around 1 10 ° C and displays a good hot-melt adhesive property on surface of glass. The film has a water absorption of 60 %. Example 14

2.6 grams of bis-chlorformate of polyester poiyol (phosgenation product of polyester polyol, Mn = 2000, made of hexanedioic acid, 1 , 4-butanediol and 1 , 2-ethanediol) and 0.30 gram of chloroformate of caster oil are dissolved in 20 ml of acetone cooled by ice water. To this are added with agitation a solution of 0.29 gram of lysine hydrochloride, 0.25 gram of sodium hydroxide in 2.5 ml of water and then triphosgene to pH around 7.5. The temperature of reaction solution is held around 5-15 ° C during the addition. It is allowed to stir at room temperature until solution becomes viscous. Organic layer is separated, and added into water under strong stirring to give a light blue polyurethane waterborne dispersion (particle size around 60 nm). The film coat of resultant polyurethane has a hardness of 6B.

Example 15

2.05 grams of bis-chlorformate of polyester polyol (phosgenation product of polyester polyol, Mn = 2000, made of hexanedioic acid, 1 , 4-butanediol and 1 , 2-ethanediol) and 0.40 gram of bis-chlorformate of 1 ,4-butanediol are dissolved in 20 ml of acetone cooled by ice water. To this is added with agitation 2 ml of aqueous solution containing about 0.21 gram of symmetrical lysine-based-diketopiperazines dihydrochoride and 0.50 gram of lysine hydrochloride, followed by the addition of 0.4 gram of sodium hydroxide in 1.5 ml of water dropwise. The temperature of reaction solution is held around 5-15 ° C and pH is maintained around 6-8 during the addition. It is then allowed to stir at room temperature until solution becomes viscous. Organic layer is added into 10 ml of water under strong stirring to give a polyurethane waterborne dispersion after distilling off the acetone. The film of resultant waterborne polyurethane has a softening point around 70 ⁰ C and displays an excellent hot-melt adhesive property on surface of glass, wood, metal and paper.

Example 16

5.2 grams of bis-chlorformate of polyester polyol (phosgenation product of polyester polyol, Mn = 2000, made of hexanedioic acid, 1 , 4-butanediol and 1 , 2-ethanediol), and 0 .75 gram of bischlorformate of 1 ,4-butanediol are dissolved in 30ml of acetone cooled by ice water. To this are added with agitation a solution of 0.81 gram of symmetrical

lysine-based-diketopiperazines dihydrochoride and 0.38 gram of piperazine (neutralized by HCI) in 3 ml of water, followed by a solution of 1.2 grams of sodium hydroxide in 1.5 ml of water while the temperature is held around 5-15° C during the addition. It is then allowed to stir at room temperature until solution becomes viscous. S-LDKP- piperazine polyurethane obtained is removed, washed with water and dried.