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

Synthetic access to the to the polyketide fragment of Apratoxin A, a biologically active cyclodepsipeptide, has been studied by several groups, with reported routes requiring over 12 steps to achieve high stereoselectivity or as few as 6 steps with compromised selectivity. Herein, we report a streamlined 9-step synthesis of the fragment featuring high enantioselectivity at C35 (>95:5), C37 (94:6), and C39 (>95:5), together with moderate diastereocontrol at C34 (~6:1) in the catalytic asymmetric crotylation step. The route offers a practical compromise between step economy and stereochemical fidelity relative to previously reported approaches. This approach provides a foundation for analogue synthesis and facilitates further studies aimed at elucidating the mechanism of its newly discovered cardiomyocyte differentiation activity.