Total Asymmetric Synthesis of the Potent Immunosuppressive Marine Natural Product Microcolin A

The total asymmetric synthesis of the potent immunosuppressive compound microcolin A is reported. The synthesis establishes the absolute stereochemistry of microcolin A as C-36 R, C-38 R, and C-4 S on the basis of the diastereoselective preparation of all four possible diastereomers of the lipid region (fragment A) and diastereoselective synthesis of fragment C starting from natural l -( S )-alanine. The strategy involves a convergent assemblage of three optically pure fragments and is amenable to chemical modifications to examine structural analogs for biological study.