Synthesis of N‐Thiophosphoryl Amino Acids via Phosphoramidite Amine‐Exchange

Abstract

N‐Thiophosphoryl amino acids were prepared rapidly and in high yield via phosphoramidite amine‐exchange in the presence of 1H‐tetrazole followed by thionation with sulfur. Formation of bis‐cyanoethyl phosphoramidothionates incorporating representative methyl esters of the amino acids alanine, glutamic acid, leucine, phenylalanine, proline, and tryptophan, were demonstrated to be successful with 2‐cyanoethyl tetraisopropylphosphorodiamidite. Mild one‐step basic deprotection of the carboxylate and phosphoramidothionate groups with LiOH afforded the N‐thiophosphonamidothioic acid derivatives of several amino acids.

Keywords:

• N‐thiophosphoryl amino acids
• Phosphoramidite amine‐exchange

Acknowledgments

This work was supported in part by the National Institutes of Health, MBRS SCORE Program‐NIGMS (Grant No. S06 GM52588‐04), a “Research Infrastructure in Minority Institutions” award from the National Center for Research Resources with funding from the Office of Research on Minority Health, National Institutes of Health (Grant No. RR11805‐02), and by a grant from The National Cancer Institute and the National Center on Minority Health and Health Disparities (Grant No. CA 96217‐01).