The polyene antibiotic myxalamide A (1) has been prepared by total synthesi
s. The synthesis illustrates a useful strategy for synthesis in which the h
igh 1,2-stereocontrol achievable with the aldol reaction can be parlayed by
other stereoselective processes so as to give compounds having two or more
stereocenters with remote relationships. Application of the Evans asymmetr
ic aldol reaction to aldehyde 13 gives the beta-hydroxy imide 17. Because t
he substrate is an alpha,beta-unsaturated aldehyde, the alcohol is allylic.
After suitable functional group manipulation, this allylic alcohol is subj
ected to enolate Claisen rearrangement (as propionate 22) to give allylsulf
ide 23, having three stereocenters with a 1,4,5-relationship. Further funct
ional group manipulation and one-carbon homologation converts this intermed
iate into 28, which is oxidized and subjected to Evans-Mislow allylsulfoxid
e rearrangement to obtain 27, having three stereocenters with a 1,2,5-relat
ionship. The synthesis of myxalamide A was completed by converting aldehyde
30 into dienyne 40. Alkyne 40 was hydroborated with catechol borane, and t
he resulting E-vinylborane was subjected to Suzuki coupling with the Z-iodo
triene 9 to provide myxalamide A (1).