Total synthesis of myxalamide A

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).