Stereoselective Synthesis of the C(1)−C(12) Fragments of Tedanolides − Application of a syn-Selective Tin(II)-Mediated Aldol Reaction and a Convertible Methoxybenzyl Protecting Group

Stereoselective synthesis of two C(1)−C(12) fragments, 3 and 4, of antitumor agents tedanolide (1) and 13-deoxytedanolide (2) was achieved by means of several regio- and/or stereoselective reactions. Ethyl ketone 14 was synthesized from methyl (S)-3-hydroxy-2-methylpropionate (16a) by way of a Weinreb amide. A highly syn-selective tin(II)-mediated aldol reaction between 14 and aldehyde 15, prepared from (R)-propionate 16b, proceeded smoothly, and subsequent reduction gave diol 13, which was transformed into 3, incorporating a C(3),C(5)-MP acetal moiety, by taking advantage of convertible MPM protecting groups. Another fragment, 4, with C(3)-O-methyl and C(5)-O-MPM groups, was also synthesized. A crucial step was the selective transformation of C(2),C(3)-diol 21 into C(2)-O-TBS, C(3)-O-Me compound 22.