A concise 9-step synthesis of the Apratoxin polyketide fragment

Synthetic access to the polyketide fragment of Apratoxin, 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 key stereocenters and moderate diastereocontrol in a 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 disovered cardiomyocyte differentiation activity.