MW‐Enhanced High‐Speed Deprotection of Boc Group Using p‐TsOH and Concommitant Formation of N‐Me‐Amino Acid Benzyl Ester p‐TsOH Salts

Abstract

A high‐speed, complete deprotection of Boc group from Boc amino acids and protected peptide esters employing p‐TsOH in toluene under microwave irradiation is found to be complete in 30 s. The deprotection can be carried out in methanol and acetonitrile also. Under the present conditions, C‐peptide benzyl esters and O‐benzyl ethers have been found to be stable. This has permitted us to carry out the synthesis of [Leu]enkephalin employing the Boc/Bzl‐group strategy. Further more, it has been found that both N ^α‐Fmoc and N ^α‐Z groups are completely stable. The present conditions can be extended for the concomitant removal of the Boc group and the formation of C‐benzyl amino acid esters as well. This has been utilized for the synthesis of N‐Me amino acid benzyl esters starting from Boc‐N‐Me amino acids in a single step.

Keywords:

• Boc group
• deprotection
• microwave irradiation
• N‐Me amino acid benzyl esters

Acknowledgments

Authors are grateful to the Council of Scientific and Industrial Research, Government of India, for financial assistance. We thank Fred Naider, City University of New York, New York, for useful discussions and Sophisticated Instruments Facility, Indian Institute of Science (I. I. Sc.), Bangalore for NMR data. B.S.P thanks Council of Scientific and Industrial Research (CSIR), Government of India, for a Senior Research Fellowship.