TECHNICAL FIELD The present invention relates to an optically active (2S, 3R)-4-cyanobutan-1, 2,3- triol derivative represented by the following formula (1) : in which R and R\'independently of one another represent hydrogen or hydroxy-protecting group, or to a process for preparing same.

Since the novel compound of formula (1) according to the present invention can be advantageously used as a precursor for preparing a 2-deoxy-L-ribose represented by the following formula (2): , the present invention further relates to a process for preparing the compound of formula (2) from the precursor compound of formula (1).

BACKGROUND ART

The compound of formula (2) is known in The Journal of Organic Chemistry, 53, 1988,2598 and The Journal of Organic Chemistry, 55, 1990,4400; useful in the research for protein-DNA interaction; used as a constituent unit of the important antisense medicines such as enantio-DNA or meso-DNA; and very useful as the intermediate for L- nucleoside drugs which are expected to have a new biological activity.

The existing process for preparing the compound of formula (2) is specifically disclosed in the above referenced literatures, and the process can be briefly summarized as the following Reaction Scheme 1.

Reaction Scheme 1 to zozos 0 S- OH Opening of the Hydrolysis zuepoxy nng HO In the above reaction, the desired compound of 2-deoxy-L-ribose (2) is produced from the starting epoxy compound via the dithiane compound as an intermediate. In this case, in order to activate the dithiane, n-butyllithium should be used as a base. However, this is a very difficult process for being applied in an industrial mass production, and thus, is not recommended.

DISCLOSURE OF INVENTION

Thus, the present inventors extensively studied to develop an industrially applicable and convenient process for preparing the compound of formula (2). As a result, we have developed the compound of formula (1), as defined above, as a novel precursor for preparing the compound of formula (2) and established a process for the preparation thereof, and then completed the present invention.

Therefore, one object of the present invention is to provide the (2S, 3R)-4- cyanobutan-1, 2,3-triol derivative of the above formula (1).

It is another object of the present invention to provide a process for the preparation of the compound of formula (1).

It is still another object of the present invention to provide a process for the preparation of the compound of formula (2) from the new starting compound of formula (1).

BEST MODE FOR CARRYING OUT THE INVENTION The present invention provides a (2S, 3R)-4-cyanobutan-1, 2,3-triol derivative of the following formula (1) :

in which R and R\'independently of one another represent hydrogen or hydroxy-protecting group.

As the hydroxy-protecting group in the present invention, any typical one in the technical field to which the present invention pertains can be used without any restriction.

But, isopropylidene, cyclohexylidene, benzylidene and benzyl are preferable and isopropylidene among them is most convenient and economic.

The present invention also provides a process for preparing the compound of formula (1). The compound of formula (1) can be conveniently prepared by introducing a cyano group into an epoxy compound represented by the following formula (3): in which R and R\'are defined as previously described, during which an opening reaction of the epoxy ring is realized. This reaction is depicted in the following Reaction Scheme 2: Reaction Scheme 2 I i OR Cyao group-introducing agent OR R0 ^ RO Opening of epoxy ring CN 0 OU (3)(1) The compound of formula (3) used as a starting material in the above reaction can easily be prepared according to the method described in Journal of the Korea75 Chemical Society, 38,11 (1994).

It is preferable to use alkali metal cyanide as the cyano group-introducing agent, and sodium cyanide or potassium cyanide among them is particularly preferable. This cyano group-introducing agent is used in an amount of 2 to 10 equivalents, preferably 6 to 10 equivalents with respect to the compound of formula (3). If it is used in an amount of less than 2 equivalents, there are some problems that the reaction time is increased and side reactions may occur. If it is used in an amount of more than 10 equivalents, it is uneconomic because there is no increase in the effect depending on the increase of the amount used.

The above reaction is optionally carried out in a solvent that does not adversely affect the reaction, and as the solvent preferable for such purpose, methanol, ethanol, 2- propanol, N, N-dimethylformamide can be mentioned. Methanol is most preferable.

The reaction may be carried out at a temperature ranging from 0 to 60 °C, suitably for about a day. However, room temperature is most preferable.

The present invention further provides a process for preparing 2-deoxy-L-ribose of formula (2) from the novel compound of formula (1) as depicted in the following Reaction Scheme 3.

Reaction Scheme 3 OR\'OH OH L 0 RO-Reduction : v- OH Hydrolyses OH HO HO n) The hydrolysis reaction of the above Reaction Scheme 3 may be carried out by warming the reactants in aqueous sodium hydroxide solution to form a lactone, and the

reduction reaction can be proceeded under the specific reaction conditions disclosed in Org.

Syn. Vol 1,321 and Bull. Chem. Jpn, Vol 45,2624-2634 (1972). For example, the reduction reaction is carried out in a solvent such as tetrahydrofuran using disiamylborane [ (Sia) 2BH] as a reducing agent. If the compound of formula (2) is prepared from the novel starting compound of formula (1) provided by the present invention according to the Reaction Scheme 3 above, mass production becomes possible needless to use a base such as n-butyllithium, and thus, desirable.

The present invention will be more specifically explained in the following Examples. However, it should be understood that these Examples are intended to illustrate the present invention but not in any manner to limit the scope of the present invention.

Example 1 Synthesis of (2S, 3R)-1, 2-O-isopropylidene-4-cyanobutan-1, 2,3-triol 5. Og of (2S, 3R)-3, 4-epoxy-1, 2-O-isopropylidenebutan-1, 2-diol was dissolved in 50 mA of absolute methanol at room temperature, and 18g of potassium cyanide was added thereto. After the mixture was stirred for 24 hours at room temperature, the reaction solution was adjusted to pH 7-8 using IN aqueous hydrochloric acid solution. This solution was distilled under reduced pressure to remove methanol. The resulting residue was extracted with dichloromethane (50 mEx3), dried over anhydrous sodium carbonate and concentrated under reduced pressure to give 4.87g (Yield 82%) of the title compound.

1H NMR (CDC13, ppm) 6 4.08 (m, 1H), 3.95 (m, 2H), 3.81 (m, 1H), 3.40 (dd, 1H), 2.72 (dd, 1H), 2.54 (dd, 1H), 1.42 (s, 3H), 1.35 (s, 3H) C NMR (CDC13, ppm) 5 22.9,24.7,26.5,66.4,68.5,77.1,109.7,117.8 IR (CDC13) cm-1 : 3200-3500 (OH), 2200 (CN)

Example 2 Synthesis of 2-deoxy-L-ribose (a) Synthesis of 2-deoxy-L-ribonolactone 8. 69g of (2S, 3R)-1, 2-O-isopropylidene-4-cyanobutan-1, 2,3-triol (l) prepared in Example 1 was dissolved in 90 mA of acetonitrile. 9 mA of IN-hydrochloric acid solution was added thereto and the resulting mixture was stirred for 1 hour at 40 °C. The solvent was removed by distillation under reduced pressure and the residue was dissolved in 15 mA of distilled water. 2.34g of sodium hydroxide dissolved in 15 mQ of distilled water and cooled to 0°C was slowly added thereto. The mixture was warmed to 80 °C and stirred for 4 hours. The solvent was removed by distillation under reduced pressure and to the residue were added 14 mA of distilled water and 1.6 mQ of conc. sulfuric acid. 50 mA of methanol was added, stirred, and filtered. Again, 50 mg of tetrahydrofuran was added, stirred, and filtered. The solvent was distilled under reduced pressure to give 5.92g (Yield 88.3%) of the title compound.

1H NMR (D20, ppm) 8 4.17-4.25 (m, 2H), 3.53 (dd, 1H), 3.42 (dd, IM, 2.71 (dd, 1H), 2.24 (dd, 1H) 13C NMR (D20, ppm) 6 32. 8,56.1,63.4,84.0,174.6 IR (CHC13) cm-1 : 3200-3400 (OH), 1764 (C=O) (b) Synthesis of 2-deoxy-L-ribose 251 mA of 2-methyl-2-butene was added to 120 mut of 2M-borane methylsulfide tetrahydrofuran solution for 5 minutes at 0 °C. After the temperature was risen to room temperature, the mixture was stirred for 2 hours and then cooled to 0 C again. 5.92g of 2-deoxy-L-ribonolactone prepared in step (a) was dissolved in 210 na of tetrahydrofuran and the resulting solution was added at 0°C. The reaction mixture was stirred for 20 hours at room temperature, cooled to 0°C, and then 1110 mA of distilled water was added thereto. The resulting mixture was stirred for further 40 minutes at room temperature.

The organic layer was separated from the reaction solution and the aqueous layer was washed with diethylether (300 aux3). The aqueous layer was concentrated under reduced pressure, the concentrate was dissolved in 100 mA of methanol, and the solvent was removed by distillation under reduced pressure. This procedure was repeated three times.

The residue thus obtained was dissolved again in 100 mA of ethanol and then filtered.

The solvent was distilled under reduced pressure to give 3.37g (Yield 56%) of the title compound.

INDUSTRIAL APPLICABILITY The compound of formula (1) newly provided by the present invention can be advantageously used for the industrial mass production of 2-deoxy-L-ribose, which is a useful intermediate in the field of manufacture of medicines.