Total Synthesis and Proof of Structure of a Human Breast Tumor (Globo-H) Antigen

The total synthesis of the Hakomori MBr1 antigen, heavily expressed on human breast tumors, is related. The construction involved the assembly of four glycals: ( 17 (twice), 18, 20, and 26 ) and an l -fucose derivative, 34 . The sensitivity of the stereochemistry of sulfonamido galactosylation by a terminal galactose ring as a function of the state of protection status of its C 4 alcohol was exploited in a key step. (See the formation of compound 51 .) The synthesis served to confirm the Hakomori assignment of structure, and paves the way for immunoconjugation. (See compound 64 .)