New applications of the n-pentenyl glycoside method in the synthesis and immunoconjugation of fucosyl GM1:: A highly tumor-specific antigen associated with small cell lung carcinoma

The synthesis of fucosyl GM(1) pentenyl glycoside 1b, and its conjugation to carrier protein KLH to give 1c is related. Bioconjugation of Ib was realized using the pendant olefin contained in the reducing end n-pentenyl glycoside (NPG). The key step of the endeavor is a stereospecific [3 + 3] coupling reaction using our sulfonamido glycosidation protocol (see 23 + 12 --> 15). Pre-installation of the NPG was required for an optimal [3 + 3] coupling yield and to allow for smooth global deprotection. The synthesis and subsequent immunocharacterization served to confirm the assigned structure of the natural tumor antigen. Fully synthetic conjugate Ic advances our program toward the goal of using a synthetic vaccine containing fucosyl GM(1) as a potential target for immune attack against small cell lung carcinoma.