Synthetic Route to Glycosyl ?-1C-(phosphino)-phosphonates as Unprecedented Stable Glycosyl Diphosphate Analogs and Their Preliminary Biological Evaluation.

ABSTRACT: The synthesis of glycosyl-?-1C-(phosphino)-phosphonates is a challenge since it has not yet been described. In this paper, we report an innovative synthetic method for their preparation from Glc-, Man-, and GlcNAc- lactone derivatives. The proposed original strategy involves the addition of the corresponding ?-hexonolactones onto the dianion of (methylphosphino) phosphonate as a key step, followed by dehydration and stereoselective addition of dihydrogen on the resulting double bond. Final deprotection provides the new glycosyl diphosphate analogs in 35%, 36%, and 10% yield over 6 steps from the corresponding ?-hexonolactones. The synthetized compounds were evaluated as inhibitors of phosphatase and diphosphatase activities and found to have complex concentration-dependent activatory and inhibitory properties on alkaline phosphatase. The synthetized tools should be useful to study other enzymes such as transferases.

SUBMITTER: Bosco M 

PROVIDER: S-EPMC7663146 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature