Chiral Synthesis of Polyketide-Derived Natural Products. 33. Stereoselective Total Synthesis of 16-Membered Macrolide Aglycons, Leuconolides and Maridonolides. Macrocyclic Stereocontrol Based on Conformational Analysis of the 16-Membered Macrolide Ring.

Sixteen-membered macrolide aglycons with different oxidation levels, leuconolide A1 (3a), leuconolide A3 (3b), midecanolide A1 (3c), maridonolide II (4a), and maridonolide I (4b), were synthesized from two carbonolide type compounds (1, 2) by stereoselective reduction and epoxidation on the 16-membered ring system. The conformational analysis of macrolide rings based on nuclear magnetic resonance measurements and MMP2 calculations is also discussed in relation to the stereoselective synthesis of the five macrolide aglycons (3a-4b).