157425-54-2Relevant academic research and scientific papers
NOVEL PYRROLE DERIVATIVES FOR THE TREATMENT OF CANCER
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Page/Page column 39, (2014/10/15)
The invention provides a method for the treatment of cancer, which method comprises the general formula (I) wherein R1, R2, R3, R4 and W are as described herein.
Preparation of alkyl-substituted indoles in the benzene portion. Part 14. Synthesis of (±)-duocarmycin SA, natural (+)-duocarmycin SA and non-natural (-)-duocarmycin SA
Muratake,Abe,Natsume
, p. 67 - 79 (2007/10/03)
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.
Total Synthesis of an Antitumor Antibiotic, (+/-)-Duocarmycin SA
Muratake, Hideaki,Abe, Itsuko,Natsume, Mitsutaka
, p. 2573 - 2576 (2007/10/02)
A 12-step total synthesis of (+/-)-duocarmycin SA (1) was achieved from a readily available pyrrole 3 by way of 7,10/11,14 and 18, using a SnCl2-mediated reaction of a singlet oxygen adduct 6 with 5, as well as the Heck and Mitsunobu reactions on 9 and 16 as key steps.
