Title:
NOVEL INTERMEDIATE, PREPARATION METHOD FOR SAME, AND APPLICATIONS THEREOF
Document Type and Number:
WIPO Patent Application WO/2022/127321
Kind Code:
A1
Abstract:
The invention relates to the field of medicament synthesis and specifically to a novel intermediate, a preparation method for same, and applications thereof. The structural formula of the novel intermediate of the present application is as represented by formula (I): in which R is a secondary amine protecting group. The present invention, based on possible biogenetic pathways of morphine derivatives, by means of a strategy for biomimetic synthesis, with an asymmetric transfer hydrogenation reaction and an intramolecular oxidative dearomatization Heck reaction in the preparation process of the intermediate serving as key reactions for total synthesis, implements the highly efficient synthesis of the morphine derivatives. The synthesis of the morphine derivatives starting from the novel intermediate provided in the present invention is characterized by significantly reduced synthesis steps, an increased yield, a reduced discharge of gaseous, liquid, and solid wastes, and inexpensive production costs.
Inventors:
QIN YONG (CN)
ZHONG WU (CN)
LI SONG (CN)
XUE FEI (CN)
SONG HAO (CN)
LIU XIAOYU (CN)
ZHANG DAN (CN)
HE HUAN (CN)
XUE FANGLIN (CN)
ZHANG MAOJIE (CN)
HU ZHAO (CN)
LI CHUNXIN (CN)
ZHU JIANQUAN (CN)
ZHANG YIFAN (CN)
TANG YU (CN)
WANG RUI (CN)
LI XUE (CN)
CAI YUKUN (CN)
ZHONG WU (CN)
LI SONG (CN)
XUE FEI (CN)
SONG HAO (CN)
LIU XIAOYU (CN)
ZHANG DAN (CN)
HE HUAN (CN)
XUE FANGLIN (CN)
ZHANG MAOJIE (CN)
HU ZHAO (CN)
LI CHUNXIN (CN)
ZHU JIANQUAN (CN)
ZHANG YIFAN (CN)
TANG YU (CN)
WANG RUI (CN)
LI XUE (CN)
CAI YUKUN (CN)
Application Number:
PCT/CN2021/123651
Publication Date:
June 23, 2022
Filing Date:
October 13, 2021
Export Citation:
Assignee:
UNIV SICHUAN (CN)
International Classes:
C07D221/28; C07D489/08
Foreign References:
| CN111205296A | 2020-05-29 | |||
| CN102459275A | 2012-05-16 |
Other References:
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HOSZTAFI SFINDOR, SFINDOR BERENYI , GEZA TOTH , SANDOR MAKLEIT: "morphine Alkaloids, Part 114 [1] A Stereohomogeneous Synthesis of N-Demethyl-N-Sub-stituted-14-Hydroxydihydromorphines", MONATSHEFTE FUR CHEMIE, vol. 123, no. 5, 31 May 1992 (1992-05-31), pages 435 - 441, XP055944167
WORLD HEALTH ORGANIZATION, 18TH WHO ESSENTIAL MEDICINES LIST, 2013
SEYA, M. J.GELDERS, S. F.ACHARA, O. U.MILANI, B.SCHOLTEN, W. K.PAIN PALLIAT, J. CARE PHARMACOTHER., vol. 25, 2011, pages 6
REED, J. W.HUDLICKY, T., ACC. CHEM. RES., vol. 48, 2015, pages 674
GUM, A.STABILE, M.: "In Studies in Natural Products Chemistry", vol. 18, 1996, ELSEVIER, pages: 43 - 154
TABER, D. F.NEUBERT, T. D.SCHLECHT, M. F.: "In Strategies and Tactics in Organic Synthesis", vol. 5, 2004, ELSEVIER, pages: 353 - 389
BARTON, D. H. R., PURE APPL. CHEM., vol. 9, 1964, pages 35
SZANTAY, C.BARCZAI-BEKE, M.PECHY, P.BLASKO, GDORNYEI, G, J. ORG. CHEM., vol. 47, 1982, pages 594
WHITE, J. D.CARAVATTI, GKLINE, T. B.EDSTROM, E.RICE, K. C.BROSSI, A., TETRAHEDRON, vol. 39, 1983, pages 2393
LIPP, AFERENC, D.GGTZ, C.GEFFE, M.VIERENGEL, N.SCHOLLMEYER, D.SCHAFER, H. J.WALDVOGEL, S. R.OPATZ, T., ANGEW. CHEM. INT. ED., vol. 57, 2018, pages 11055
GALANIE, S.; THODEY, K.; TRENCHARD, I. J.; FILSINGER, I. M.; SMOLKE, C. D., SCIENCE, vol. 349, 2015, pages 1095
WANG PINGPINGYANG CHENGSHUAILI XIAODONGJIANG YUGOYAN XINGZHOU ZHIHUA, ORGANIC CHEMISTRY, vol. 38, 2018, pages 2199
QIN, Y, CCS CHEM., vol. 3, 2021, pages 1376
HOSZTAFI SFINDOR, SFINDOR BERENYI , GEZA TOTH , SANDOR MAKLEIT: "morphine Alkaloids, Part 114 [1] A Stereohomogeneous Synthesis of N-Demethyl-N-Sub-stituted-14-Hydroxydihydromorphines", MONATSHEFTE FUR CHEMIE, vol. 123, no. 5, 31 May 1992 (1992-05-31), pages 435 - 441, XP055944167
WORLD HEALTH ORGANIZATION, 18TH WHO ESSENTIAL MEDICINES LIST, 2013
SEYA, M. J.GELDERS, S. F.ACHARA, O. U.MILANI, B.SCHOLTEN, W. K.PAIN PALLIAT, J. CARE PHARMACOTHER., vol. 25, 2011, pages 6
REED, J. W.HUDLICKY, T., ACC. CHEM. RES., vol. 48, 2015, pages 674
GUM, A.STABILE, M.: "In Studies in Natural Products Chemistry", vol. 18, 1996, ELSEVIER, pages: 43 - 154
TABER, D. F.NEUBERT, T. D.SCHLECHT, M. F.: "In Strategies and Tactics in Organic Synthesis", vol. 5, 2004, ELSEVIER, pages: 353 - 389
BARTON, D. H. R., PURE APPL. CHEM., vol. 9, 1964, pages 35
SZANTAY, C.BARCZAI-BEKE, M.PECHY, P.BLASKO, GDORNYEI, G, J. ORG. CHEM., vol. 47, 1982, pages 594
WHITE, J. D.CARAVATTI, GKLINE, T. B.EDSTROM, E.RICE, K. C.BROSSI, A., TETRAHEDRON, vol. 39, 1983, pages 2393
LIPP, AFERENC, D.GGTZ, C.GEFFE, M.VIERENGEL, N.SCHOLLMEYER, D.SCHAFER, H. J.WALDVOGEL, S. R.OPATZ, T., ANGEW. CHEM. INT. ED., vol. 57, 2018, pages 11055
GALANIE, S.; THODEY, K.; TRENCHARD, I. J.; FILSINGER, I. M.; SMOLKE, C. D., SCIENCE, vol. 349, 2015, pages 1095
WANG PINGPINGYANG CHENGSHUAILI XIAODONGJIANG YUGOYAN XINGZHOU ZHIHUA, ORGANIC CHEMISTRY, vol. 38, 2018, pages 2199
QIN, Y, CCS CHEM., vol. 3, 2021, pages 1376
Attorney, Agent or Firm:
CHENGDU JEWEIHO INTELLECTUAL PROPERTY LAW FIRM (CN)
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