Constrained 3,6‐Anhydro‐Heptosides: Synthesis by a DAST‐Induced Debenzylative Reaction, and Reactivity Profile

Abstract

We report the first synthesis of a conformationally constrained 3,6‐anhydroheptoside analogue of D‐glycero‐D‐manno‐heptopyranose 7‐phosphate by a DAST (diethylaminosulfur trifluoride)‐induced intramolecular cycloetherification. The reactivity of a series of constrained bicyclic 3,6‐anhydro‐thioheptosides as glycosyl donors was also studied in glycosylation reactions and compared with the reactivities of related unconstrained mannose and heptose scaffolds. Competition experiments confirmed that in the D‐manno‐heptose series, a reversal of chair conformation leads to an enhancement of the anomeric reactivity.

Debenzylative Cycloetherification: An Overlooked Key Strategy for Complex Tetrahydrofuran Synthesis

“…In 2013, Vincent and Tikad explored the DBCE reaction to perform the synthesis of conformationally constrained methyl 3,6‐anhydro‐ l ‐glycero‐α‐ d ‐manno‐heptopyranoside 7‐phosphate 106 , an analogue of methyl d ‐glycero‐ d ‐gluco‐heptopyranose 7‐phosphate 107 , which is the best inhibitor of both enzymes GmhA (IC 50 =34 μ m ) and HldE (IC 50 =9.4 μ m ), the two first enzymes of the bacterial heptose biosynthetic pathway (Scheme ) . Based on the debenzylative cyclization induced by DAST as a key step in this strategy, the target 3,6‐anhydroheptosides 103 – 105 were achieved after a few hours in good to excellent yields, whatever the nature of starting l ‐heptoside used ( 100 – 102 ; Scheme ).…”

Diethylaminosulfur Trifluoride (DAST) Mediated Transformations Leading to Valuable Building Blocks and Bioactive Compounds

“…Diethylaminosulfur trifluoride constituted promotor of intramolecular cycloetherification (Scheme 43). [68] Target molecules play an important role in the mortality of many human pathogens. [69] They might be a useful tool as a conformational probe of enzymatic reactions.…”

“…[69] They might be a useful tool as a conformational probe of enzymatic reactions. [68] Initially, in the presence of DAST, the OH group in the C6 position was activated. Further, intermediate 203 was transformed into benzyloxonium 204 by attack of the free electron pair of benzyloxy group at C3.…”

The Construction of Anhydro Monosaccharides

“…The usefulness of DAST is not limited to the synthesis of 3,6‐anhydro hexosides. Tikad and co‐workers investigated the reactivity profiles of constrained 3,6‐heptosides, the structure of which was constructed by DAST‐induced intramolecular cyclization of the corresponding heptosides ( 105 and 106 ; Scheme ) . The most obvious advantage of DAST is the mild reaction conditions employed, which are suitable for substrates sensitive to either acidic or basic environments.…”