Synthesis and Evaluation of Sulfobacin A and Analogues for Their Roles in Immunological Recognition.

We report the total synthesis of sulfobacin A (1) and its stereoisomeric analogue 1a via dynamic kinetic resolution of racemic precursors using catalytic asymmetric reactions to establish three stereogenic centers without chiral building blocks. Late-stage optimization of the amide coupling improved the overall yield of 1 to 7.8%. Preliminary biological evaluation reveals that sulfobacin A is recognized by multiple T-cell subsets (CD4, CD8, and NKT cells) when presented by multiple CD1 tetramers, indicating that this sulfonolipid can engage T cells that influence both innate (NKT) and adaptive (CD4 and CD8) immune responses. Moreover, our data suggest that modification of the lipid headgroup or alteration to a monoacyl lipid diminishes CD1-mediated T-cell recognition.