A two step synthesis of a key unit B precursor of cryptophycins by asymmetric hydrogenation

Benedikt Sammet,Norbert Sewald,Mathilde Brax

doi:10.3762/bjoc.7.32

Abstract

A novel highly enantioselective two step access to a unit B precursor of cryptophycins in good yields from commercially available starting materials has been developed. The key step is an asymmetric hydrogenation using the commercially available [(COD)Rh-(R,R)-Et-DuPhos]BF4 catalyst. The synthetic route provides the advantage of less synthetic steps, proceeds with high yields and enantioselectivity, and avoids hazardous reaction conditions.

Highlights

Cryptophycins are macrocyclic depsipeptides, which show very high cytotoxicity even against multidrug-resistant cell lines
We envisaged a two step synthesis for the unit B precursor 4 (Scheme 1) from commercially available non-toxic starting materials based on an asymmetric hydrogenation approach to make the unit B precursor synthesis shorter and safer
There is a whole variety of possible stereoselective synthetic methods available to synthesize modified α-amino acids, such as the classical Schöllkopf-method [10] or catalytic approaches [11,12]

Summary

Introduction

Cryptophycins are macrocyclic depsipeptides, which show very high cytotoxicity even against multidrug-resistant cell lines. A novel highly enantioselective two step access to a unit B precursor of cryptophycins in good yields from commercially available starting materials has been developed. The key step is an asymmetric hydrogenation using the commercially available [(COD)Rh(R,R)-Et-DuPhos]BF4 catalyst. The synthetic route provides the advantage of less synthetic steps, proceeds with high yields and enantioselectivity, and avoids hazardous reaction conditions.

Results

Conclusion