Total Synthesis of Pseudomonic Acid C

Article abstract of DOI:10.1021/jo00253a021

Two approaches to the synthesis of aldehyde 28, a key intermediate in the total synthesis of pseudomonic acid C, were developed.One asymmetric route from the chiral hydroxy ester 11 proceeded in 13 steps via the hydroxy lactone 17.A shorter approach involved the Lewis acid catalyzed cycloaddition of formaldehyde to the chiral diene 23a to give 22a, which was separated from its diastereomer and then converted into 28 in seven steps.The introduction of the C-8 side chain was initially accomplished by Julia coupling of 28 with the sulfone anion derived from 40 to give the olefin 34.The stereoselective preparation of 34 was also carried out, via the ester 46a, by a novel ester enolate Claisen rearrangement of the silyl-protected glycolate ester 44.A third approach directed toward the synthesis of the side chain entailed controlling the C-10 stereochemistry of the benzyl-protected glycolate ester 48 by reduction of a precursor propargyl ketone 27 with Alpine borane.Ester enolate Claisen rearrangement then gave the ester 46b with excellent stereocontrol.