A Concise 9-Step Synthesis of the Apratoxin A Polyketide Fragment

Synthetic access to the polyketide fragment of Apratoxin, a biologically active cyclodepsipeptide, hasbeen studied by several groups, with reported routes requiring over 12 steps to achieve highstereoselectivity or as few as 6 steps with compromised selectivity. Herein, we report a streamlined 9-step synthesis of the fragment featuring high enantioselectivity at key stereocenters and moderatediastereocontrol in a catalytic asymmetric crotylation step. The route offers a practical compromisebetween step economy and stereochemical fidelity relative to previously reported approaches. Thisapproach provides a foundation for analogue synthesis and facilitates further studies aimed atelucidating the mechanism of its newly discovered cardiomyocyte differentiation activity.