Total synthesis of the cytotoxic threo, trans, threo, trans, threo annonaceous acetogenin asimin and its C-10 epimer: unambiguous confirmation of absolute stereochemistry.
A convergent synthesis of asimin (1) and its C-10 epimer 33 is reported. The essential features of this synthesis include (a) the addition of an enantioenriched gamma-OMOM allylic indium reagent to a core C-23 aldehyde precursor to install the C-24-C-34 segment with concomitant introduction of the C-24 and C-23 stereocenters; (b) the addition of an enantioenriched gamma-OMOM allylic indium reagent to a core C-16 aldehyde to install the C-10-C-15 segment with formation of the C-15 and C-16 stereocenters, (c) the addition of a dialkyl zinc reagent, catalyzed by a chiral triflamide-Ti(O-i-Pr)(4) complex, to introduce the C-1-C-9 segment with creation of either the 10(R) or 10(S) stereocenters; and (d) aldol condensation of the foregoing C-1-C-34 segment with OTBS-protected lactic aldehyde to incorporate the C-35-C-37 butenolide segment. Removal of the three MOM protecting groups was achieved with aqueous HCl in THF. The 10(R) diastereomer was found to correspond to natural asimin.
Marshall
J A
JA
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901, USA. jam5x@virginia.edu
Jiang
H
H
D000438:Alcohols; D003500:Cyclization; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry; D007536:Isomerism; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation
D000438:Alcohols; D005663:Furans; D007783:Lactones; C088264:asimin