Chemical and Pharmaceutical Bulletin p. 67 - 79 (1996)
Update date:2022-08-05
Topics:
Muratake
Abe
Natsume
Total synthesis of duocarmycin SA (1), an extremely potent cytotoxic antibiotic, was achieved in the racemic form at first by effectively utilizing two reactions as key steps, (i) an intramolecular Heck reaction of the benzyl ether 21a, derived from a dihydropyridine 13a and a pyrrole derivative 11, to form tricyclic compounds 25a and 26a, and (ii) a modified Mitsunobu reaction on the diol derivative 40 for the construction of compound 41 having the pivotal pharmacophore of a cyclopropanoindolinone partial structure, which is critical for the high biological activities of 1. Next, optical resolution of an intermediary racemic secondary alcohol 50 was cleanly attained by derivatizing it to (R)-O-methylmandelates 52 and 53, and the resulting chiral alcohols (+)-50 and (-)-50 were respectively transformed into unnatural (-)-1 and natural (+)-1. Finally inversion of the secondary alcohol (+)-50 to the enantiomer (-)-50 was effected by using the Mitsunobu reaction. This constitutes an enantio-convergent total synthesis of natural duocarmycin SA (1) starting from a racemic compound.
View MoreGlobal United Biotechnology Inc.
Contact:+86-21-61618568
Address:Room 309, Building 6, NO.135, Jinyu Road, Pudong
Contact:+86-021-50792271
Address:Building 24A, 300 Chuantu Road, Chuansha, Pudong new area, Shanghai, China, 201202
ZHIJIANG ZENVA SINO COMMERCE AND TRADE CO., LTD.
website:http://www.zenvasino.com
Contact:+86-138-72658998
Address:Shibeishan Road,Zhijiang, Hubei, China
website:http://www.antaibio.com
Contact:0086-21-65663057
Address:Room 2108, Building 2，No. 489 Zhengli Road，200433
jiangsu senxuan pharmaceutical and chemical co.,ltd
Contact:86-523-87982810
Address:hongqiao industrial zone,taixing,jiangsu china
Doi:10.1021/jm00039a012
(1994)Doi:10.1016/j.ica.2014.01.014
(2014)Doi:10.1039/c4cc00251b
(2014)Doi:10.1016/j.ejmech.2014.01.050
(2014)Doi:10.1016/S0040-4039(00)78197-4
(1994)Doi:10.1039/c3dt52785a
(2014)
