Catalytic Asymmetric Aldol Equivalents for an Enantioselective Total Synthesis of Apoptolidin C

[摘要] Apoptolidin C is a biologically active polypropionate macrolide isolated from the soil bacteria Nocardiopsis sp.The work presented herein highlights a novel approach to synthesizing the core of the natural product, apoptolidinone C, as well as a de-novo synthesis of the C9 sacharide.Our synthesis utilizes a catalytic asymmetric approach to the construction of the complex polypropionate arrays contained in apoptolidin through the use of our acyl halide-aldehyde cyclocondensation (AAC) reaction.Employing the AAC technology using cinchona alkaloid derived catalysts, as well as the complementary chiral aluminum catalysts, we have successfully demonstrated a catalytic and asymmetric synthesis of the aglycone core of apoptolidin C. In addition, we have demonstrated the asymmetric synthesis of the C9 saccharide from achiral starting materials.

[发布机构] the University of Pittsburgh