title: Total synthesis, stereochemical assignment, and biological activity of chamuvarinin and structural analogues.
abstract: A highly stereocontrolled synthesis of (+)-chamuvarinin has been completed in 1.5% overall yield over 20 steps. The key fragment coupling reactions were the addition of alkyne 8 to aldehyde 7 (under Felkin-Anh control), followed by the two step activation/cyclization to close the C20-C23 2,5-cis-substituted tetrahydrofuran ring and a Julia-Kocienski olefination at C8-C9 to introduce the terminal butenolide. The inherent flexibility of our coupling strategy led to a streamlined synthesis with 17 steps in the longest sequence (2.2% overall yield), in which the key bond couplings are reversed. In addition, a series of structural analogues of chamuvarinin have been prepared and screened for activity against HeLa cancer cell lines and both the bloodstream and insect forms of Trypanosoma brucei, the parasitic agent responsible for African sleeping sickness.
authors: EaStCHEM School of Chemistry, Biomedical Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, KY16 9ST, UK. gjf1@st-andrews.ac.uk
authors: Gordon J
authors: GJ
authors: Florence
authors: Joanne C
authors: JC
authors: Morris
authors: Ross G
authors: RG
authors: Murray
authors: Raghava R
authors: RR
authors: Vanga
authors: Jonathan D
authors: JD
authors: Osler
authors: Terry K
authors: TK
authors: Smith
mesh_terms: D054378:Acetogenins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000447:Aldehydes / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D003500:Cyclization; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D013237:Stereoisomerism; D014346:Trypanosoma brucei brucei / Q000187:drug effects
chemical_list: D054378:Acetogenins; D000447:Aldehydes; C488316:chamuvarinin