Synthesis of Thiol-Containing Amino Acids Through Alkylation of Glycinate Ketimine

Abstract

A general synthetic route for the synthesis of thiol-containing amino acids through alkylation of glycinate ketimine followed by hydrolysis was developed in this work. The common problems associated with the instability of ketimines and thioesters were solved by optimization of both synthetic and purification conditions. A series of thiol-containing amino acids were obtained in good yields. This method could be readily extended to the synthesis of other thiol-containing amino acids, which are important intermediates in pharmaceutical research and medical applications.

GRAPHICAL ABSTRACT

Keywords:

• Alkylation
• ketimine
• thiol-containing amino acids

ACKNOWLEDGMENT

This work was supported by the National Special Fund for State Key Laboratory of Bioreactor Engineering of China (2060204).

Notes

^a Reactions were carried out at 40 °C (Entries 1–3), 110 °C (entry 4), 90 °C (entry 5) and 25 °C (entry 6).

^b DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene.

^c Isolated yield.

^d The alkylation was run under phase-transfer conditions with 50% aqueous KOH as base, dichloromethane (DCM) and toluene (7:3) as solvent, and tetrabutylammonium bromide as catalyst.