Total synthesis and stereochemical reassignment of (+)-dolastatin 19, a cytotoxic marine macrolide isolated from Dolabella auricularia |
| |
Authors: | Ian Paterson Alison D. Findlay Gordon J. Florence |
| |
Affiliation: | University Chemical Laboratory, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK |
| |
Abstract: | Using conformational analysis and biogenetic considerations, a revised configurational assignment for the cytotoxic marine macrolide dolastatin 19 is proposed, together with its validation by completion of the first total synthesis. Key features of the highly stereocontrolled route include an asymmetric vinylogous Mukaiyama aldol reaction to simultaneously install both the remote C13 stereocenter and the C10-C11 (E)-trisubstituted olefin, two sequential 1,4-syn boron-mediated aldol reactions, and a late-stage, α-selective Mukaiyama glycosylation to append the l-rhamnose-derived pyranoside. |
| |
Keywords: | Macrolide Cytotoxic Conformational analysis Stereochemical reassignment Aldol reaction Glycosylation |
本文献已被 ScienceDirect 等数据库收录! |
|