Enantioselective synthesis of (-)-terpestacin and (-)-fusaproliferin: clarification of optical rotational measurements and absolute configurational assignments establishes a homochiral structural series.
An enantioselective synthesis of the syncytium formation inhibitor (-)-terpestacin (1, 19 steps, 5.8% yield from the allylation product of (R,R)-pseudoephedrine propionamide, 3) and the fungal metabolite (-)-fusaproliferin (2, 21 steps, 5.3% yield from 3) in their natural configurations is described. The route employs a series of stereoselective enolate alkylation reactions to establish the initial stereogenic center, set the quaternary carbon configuration, close the 15-membered ring, and introduce the side-chain residue with proper stereocontrol. Careful analysis of our synthetic materials alongside natural samples has revealed that several errors were made in the earlier measurements of optical rotation or in the absolute stereochemical assignments of these natural products. Clarifying all discrepancies, we show here that natural terpestacin (1) is levorotatory, not dextrorotatory as originally described, but was correctly assigned as the (1S,11S,15R,23S)-enantiomer. Fusaproliferin (2) is levorotatory, as reported, but is in fact the (1S,11S,15R,23S)-enantiomer and not the antipodal configuration originally assigned.
Myers
Andrew G
AG
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.
Siu
Michael
M
Ren
Feng
F
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism; D013729:Terpenes / Q000138:chemical synthesis* / Q000737:chemistry
D000900:Anti-Bacterial Agents; D001643:Bridged Bicyclo Compounds; D013729:Terpenes; C093577:fusaproliferin; C080890:terpestacin