New Convenient Reagents for Chemoselective N‐Alkoxycarbonylation of (S)‐Isoserine: Application in the Isepamicin Synthesis

Abstract

A synthesis of a series of N‐alkoxycarbonyl mercaptobenzothiazoles (MBTs) and their application as reagents for chemoselective protection of amino group are presented herein. It was shown that all new reagents, Z‐MBT, Fmoc‐MBT, Phoc‐MBT, and Tec‐MBT, are highly effective in the selective N‐alkoxycarbonylation of (S)‐isoserine. The transformation is a simple, fast, and low‐cost protocol, which is applicable in scale‐up experiments. The starting MBT was fully recovered at the end of the process, which is an additional advantage of the method. The efficiency of the Z‐reagent was also demonstrated by the selective protection of both gentamicin B and (S)‐isoserine before their peptide‐type coupling in the synthesis of the aminoglycoside antibiotic isepamicin.

Keywords:

• chemoselective
• gentamicin B
• isepamicin
• mercaptobenzothiazole
• N‐protection
• (S)‐isoserine

Acknowledgments

We gratefully thank ACTAVIS AD, Sofia, for supplying us with gentamicin B and for the financial support.