Development of a third-generation total synthesis of (+)-discodermolide: an expedient Still-Gennari-type fragment coupling utilizing an advanced beta-ketophosphonate |
| |
Authors: | Paterson Ian Lyothier Isabelle |
| |
Affiliation: | University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK. ip100@cam.ac.uk |
| |
Abstract: | [structure: see text] A novel total synthesis of the complex polyketide discodermolide, a promising anticancer agent of marine sponge origin, has been completed in 11.1% overall yield over 21 linear steps. This third-generation approach features an unprecedented Still-Gennari-type HWE olefination reaction between advanced C1-C8 beta-ketophosphonate 61 and C9-C24 aldehyde 7, introducing the (8Z)-alkene with 10:1 selectivity. The stereotetrad found in the C1-C8 subunit 61 was established via a highly diastereoselective boron-mediated aldol reaction/in situ reduction between ketone (S)-8 and 3-benzyloxypropanal. The (7S)-configuration was installed by the reduction of enone 73 with K-Selectride. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|