Zaragozic Acid A/Squalestatin S1: Synthetic and Retrosynthetic Studies

Abstract

Step by step the first total synthesis was approached: of the zaragozic acids/ squalestatins showing potential therapeutic value for lowering the serum cholesterol concentration, zaragozic acid A/squalestatin SI (1), the most abundant member of a new class of naturally occurring products, has now been synthesized via the key intermediates 2 and 3. Initially the projected final sequence (2 → 1) was achieved, and the side chains attached to C1 and C6 were prepared through efficient asymmetric syntheses. The first synthesis of the highly oxygenated “core”, which is characteristic of this class of natural products, was achieved from a simple prochiral diene via intermediate 3. Finally the synthetic route 3 → 2 was developed to successfully complete the total synthesis. Bn  benzyl, PMB  para-methoxybenzyl, TMS  trimethylsilyl.