Seven‐Step Synthesis of All‐Nitrogenated Sugar Derivatives Using Sequential Overman Rearrangements

Abstract

Scheme 3. Syntheses of hexose-type peracetylated ANSs through five sequential Overman rearrangements. A) Synthesis of D-galactofuranose-type pAc-ANS. B) Synthesis of D-glucofuranose-type pAc-ANS. Scheme 4. Transformation of D-arabinofuranose-type pAc-ANS (22). Boc = tert-butoxycarbonyl, DMAP = 4-dimethylaminopyridine, MS = molecular sieves, TMS = trimethylsilyl.

Synthesis and Evaluation of Saponins with All-Nitrogenated Sugars

“…Recently, we reported the synthesis of all-nitrogenated sugars (ANS) by replacing all oxygen atoms with nitrogen atoms through sequential Overman rearrangements (Figure 1b ). 8 We could synthesize various types of ANSs, such as pAc-ANS 6 , which is derived from l -arabinose ( 5 ). Introduction of pAc-ANS 6 to cholesterol was achieved by glycosylation using TMSOTf, providing ANS-cholesterol 7 with cytotoxicity.…”

“…We improved the glycosylation conditions using pAc-ANS 6 and cholesterol ( 9 ) (Table 1 ). The initial conditions, 8 under which 5 equivalents of TMSOTf as the Lewis acid and 100 equivalents of cholesterol ( 9 ) as the aglycon were used in (CH 2 Cl) 2 , gave 7 8 9 in low yield (entry 1). Use of THF instead of (CH 2 Cl) 2 yielded both 7 and minor anomer 10 (entry 2).…”