Title:
SYNTHESIS METHOD FOR NUCIFERINE OR DERIVATIVE THEREOF, NUCIFERINE DERIVATIVE AND APPLICATION THEREOF
Document Type and Number:
WIPO Patent Application WO/2023/178809
Kind Code:
A1
Abstract:
A synthesis method for nuciferine or a derivative thereof, a nuciferine derivative and an application thereof. A compound having a structure shown in formula IV and R-X undergo a Schotten-Baumann reaction, and then nuciferine having a structure shown in formula VI or a derivative thereof is obtained by means of carbon-hydrogen bond activation. Further, the compound having the structure as shown in formula IV is obtained by an acyl chlorination reaction, a nucleophilic substitution reaction, a Bischler-Napieralski reaction, and a reduction reaction with 2-bromophenylacetic acid as a starting material. The nuciferine derivative can be used for preparing lipid-lowering drugs. The compound having the structure shown in formula IV and the nuciferine derivative having the structure shown in formula VI are shown as follows: formula IV and formula VI.
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Inventors:
TANG XUCHONG (CN)
ZHAO YINGWEI (CN)
LI XUAN (CN)
CAO LIPING (CN)
ZHAO YINGWEI (CN)
LI XUAN (CN)
CAO LIPING (CN)
Application Number:
PCT/CN2022/092097
Publication Date:
September 28, 2023
Filing Date:
May 11, 2022
Export Citation:
Assignee:
UNIV HUAQIAO (CN)
BAYECAO HEALTH INDUSTRY RES INSTITUTE XIAMEN CO LTD (CN)
BAYECAO HEALTH INDUSTRY RES INSTITUTE XIAMEN CO LTD (CN)
International Classes:
C07D221/18; A61P3/04; A61P3/06; C07D217/18
Foreign References:
| CN110343069A | 2019-10-18 |
Other References:
RAYANIL KANOK-ON, PREMPREE CHOLTHICHA, NIMGIRAWATH SURACHAI: "The first total syntheses of (±)-norphoebine, dehydrophoebine, oxophoebine, dehydrocrebanine, oxocrebanine and uthongine and their cytotoxicity against three human cancer cell lines", JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH, GORDON AND BREACH, CHUR, CH, vol. 18, no. 11, 1 November 2016 (2016-11-01), CH , pages 1042 - 1056, XP093094331, ISSN: 1028-6020, DOI: 10.1080/10286020.2016.1177025
DATABASE REGISTRY ANONYMOUS : "- 4H-Dibenzo[de,g]quinoline, 6-benzoyl-5,6,6a,7-tetrahydro-1,2-dimethoxy-, (R)- (9CI) (CA INDEX NAME)", XP093094351, retrieved from STN
DATABASE REGISTRY ANONYMOUS : "- Ethanone, 1-[(6aR)-4,5,6a,7-tetrahydro-1,2-dimethoxy-6Hdibenzo[de,g]quinolin-6-yl]- (CA INDEX NAME)", XP093094354, retrieved from STN
DATABASE REGISTRY ANONYMOUS : "- 4H-Dibenzo[de,g]quinoline, 5,6,6a,7-tetrahydro-1,2-dimethoxy-6-(2- propynyl)-, (R)- (9CI) (CA INDEX NAME)", XP093094355, retrieved from STN
DATABASE REGISTRY ANONYMOUS : "- 4H-Dibenzo[de,g]quinoline, 5,6,6a,7-tetrahydro-1,2-dimethoxy-6-(2- propenyl)-, (R)- (9CI) (CA INDEX NAME)", XP093094356, retrieved from STN
DATABASE REGISTRY ANONYMOUS : "- 4H-Dibenzo[de,g]quinoline, 5,6,6a,7-tetrahydro-1,2-dimethoxy-6-propyl-, (R)- (9CI) (CA INDEX NAME)", XP093094358, retrieved from STN
DATABASE REGISTRY ANONYMOUS : "- 4H-Dibenzo[de,g]quinoline, 6-ethyl-5,6,6a,7-tetrahydro-1,2-dimethoxy-, (R)- (9CI) (CA INDEX NAME)", XP093094361, retrieved from STN
SILVA ANDREA G., VILA LAURA, MARQUES PATRICE, MORENO LAURA, LOZA MABEL, SANZ MARÍA-JESÚS, CORTES DIEGO, CASTRO MARIÁN, CABEDO NURI: "1-(2′-Bromobenzyl)-6,7-dihydroxy- N -methyl-tetrahydroisoquinoline and 1,2-Demethyl-nuciferine as Agonists in Human D 2 Dopamine Receptors", JOURNAL OF NATURAL PRODUCTS, AMERICAN CHEMICAL SOCIETY, US, vol. 83, no. 1, 24 January 2020 (2020-01-24), US , pages 127 - 133, XP093094334, ISSN: 0163-3864, DOI: 10.1021/acs.jnatprod.9b00921
YU, YUE ET AL.: "Akkermansia Muciniphila: a Potential Novel Mechanism of Nuciferine to Improve Hyperlipidemia", BIOMEDICINE & PHARMACOTHERAPY, vol. 133, 26 November 2020 (2020-11-26), XP086416791, ISSN: 0753-3322, DOI: 10.1016/j.biopha.2020.111014
LAFRANCE MARC, BLAQUIÈRE NICOLE, FAGNOU KEITH: "Direct intramolecular arylation of unactivated arenes: application to the synthesis of aporphine alkaloids", CHEMICAL COMMUNICATIONS, ROYAL SOCIETY OF CHEMISTRY, UK, no. 24, 1 January 2004 (2004-01-01), UK , pages 2874 - 2875, XP093094335, ISSN: 1359-7345, DOI: 10.1039/B410394G
DATABASE REGISTRY ANONYMOUS : "- 4H-Dibenzo[de,g]quinoline, 6-benzoyl-5,6,6a,7-tetrahydro-1,2-dimethoxy-, (R)- (9CI) (CA INDEX NAME)", XP093094351, retrieved from STN
DATABASE REGISTRY ANONYMOUS : "- Ethanone, 1-[(6aR)-4,5,6a,7-tetrahydro-1,2-dimethoxy-6Hdibenzo[de,g]quinolin-6-yl]- (CA INDEX NAME)", XP093094354, retrieved from STN
DATABASE REGISTRY ANONYMOUS : "- 4H-Dibenzo[de,g]quinoline, 5,6,6a,7-tetrahydro-1,2-dimethoxy-6-(2- propynyl)-, (R)- (9CI) (CA INDEX NAME)", XP093094355, retrieved from STN
DATABASE REGISTRY ANONYMOUS : "- 4H-Dibenzo[de,g]quinoline, 5,6,6a,7-tetrahydro-1,2-dimethoxy-6-(2- propenyl)-, (R)- (9CI) (CA INDEX NAME)", XP093094356, retrieved from STN
DATABASE REGISTRY ANONYMOUS : "- 4H-Dibenzo[de,g]quinoline, 5,6,6a,7-tetrahydro-1,2-dimethoxy-6-propyl-, (R)- (9CI) (CA INDEX NAME)", XP093094358, retrieved from STN
DATABASE REGISTRY ANONYMOUS : "- 4H-Dibenzo[de,g]quinoline, 6-ethyl-5,6,6a,7-tetrahydro-1,2-dimethoxy-, (R)- (9CI) (CA INDEX NAME)", XP093094361, retrieved from STN
SILVA ANDREA G., VILA LAURA, MARQUES PATRICE, MORENO LAURA, LOZA MABEL, SANZ MARÍA-JESÚS, CORTES DIEGO, CASTRO MARIÁN, CABEDO NURI: "1-(2′-Bromobenzyl)-6,7-dihydroxy- N -methyl-tetrahydroisoquinoline and 1,2-Demethyl-nuciferine as Agonists in Human D 2 Dopamine Receptors", JOURNAL OF NATURAL PRODUCTS, AMERICAN CHEMICAL SOCIETY, US, vol. 83, no. 1, 24 January 2020 (2020-01-24), US , pages 127 - 133, XP093094334, ISSN: 0163-3864, DOI: 10.1021/acs.jnatprod.9b00921
YU, YUE ET AL.: "Akkermansia Muciniphila: a Potential Novel Mechanism of Nuciferine to Improve Hyperlipidemia", BIOMEDICINE & PHARMACOTHERAPY, vol. 133, 26 November 2020 (2020-11-26), XP086416791, ISSN: 0753-3322, DOI: 10.1016/j.biopha.2020.111014
LAFRANCE MARC, BLAQUIÈRE NICOLE, FAGNOU KEITH: "Direct intramolecular arylation of unactivated arenes: application to the synthesis of aporphine alkaloids", CHEMICAL COMMUNICATIONS, ROYAL SOCIETY OF CHEMISTRY, UK, no. 24, 1 January 2004 (2004-01-01), UK , pages 2874 - 2875, XP093094335, ISSN: 1359-7345, DOI: 10.1039/B410394G
Attorney, Agent or Firm:
BEIJING GAOWO LAW FIRM (CN)
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