Total Synthesis of Meayamycin B

Meayamycin B is currently the most potent modulator of the splicing factor 3b subunit 1 and used by dozens of research groups. However, current supply for this natural product analogue is limited because of the lengthy synthetic scheme. Here, we report a more concise, more cost-effective, and greene...

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Bibliographic Details
Published in:Journal of organic chemistry 2020-04, Vol.85 (7), p.4637-4647
Main Authors: Bressin, Robert K, Osman, Sami, Pohorilets, Ivanna, Basu, Upamanyu, Koide, Kazunori
Format: Article
Language:English
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Summary:Meayamycin B is currently the most potent modulator of the splicing factor 3b subunit 1 and used by dozens of research groups. However, current supply for this natural product analogue is limited because of the lengthy synthetic scheme. Here, we report a more concise, more cost-effective, and greener synthesis of this compound by developing and employing a novel asymmetric reduction of a prochiral enone to afford an allylic alcohol with high enantioselectivity. In addition to this reaction, this synthesis highlights a scalable Mukaiyama aldol reaction, Nicolaou-type epoxide opening reaction, stereoselective Corey–Chaykovsky-type reaction, and a modified Horner–Wadsworth–Emmons Z-selective olefination. We also discuss a Z–E isomerization during the α,β-unsaturated amide formation. The new synthesis of meayamycin B consists of 11 steps in the longest linear sequence and 24 total steps.
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.9b03370