A new approach toward the total synthesis of (+)-batzellaside B

Jolanta Wierzejska,Shin-Ichi Motogoe,Masaki Takahashi,Hidemi Yoda,Yuto Makino,Tetsuya Sengoku

doi:10.3762/bjoc.8.210

Abstract

A new synthetic approach to (+)-batzellaside B from naturally abundant L-pyroglutamic acid is presented in this article. The key synthetic step involves Sharpless asymmetric dihydroxylation of an olefinic substrate functionalized with an acetoxy group to introduce two chiral centres diastereoselectively into the structure. Heterocyclic hemiaminal 4, which could be converted from the resulting product, was found to provide stereospecific access to enantiomerically enriched allylated intermediate, offering better prospects for the total synthesis of this natural product.

Highlights

Iminosugars, monosaccharide analogues in which the endocyclic oxygen has been replaced by nitrogen, display beneficial therapeutic activity as sugar-mimicking glycosidase inhibitors [1,2,3,4]
We communicated the first total synthesis of (+)-batzellaside B (1b) by the use of L-arabinose, wherein the absolute stereochemistry of this natural product was completely established by the modified Mosher analysis of a synthetic intermediate prepared through a separate route (Scheme 1) [19]
The synthesis began with the preparation of N-Boc-protected γ-lactam 8 by stepwise functionalization of L-pyroglutamic acid, using literature procedures (Scheme 2) [22]

Summary

Introduction

Iminosugars, monosaccharide analogues in which the endocyclic oxygen has been replaced by nitrogen, display beneficial therapeutic activity as sugar-mimicking glycosidase inhibitors [1,2,3,4]. We communicated the first total synthesis of (+)-batzellaside B (1b) by the use of L-arabinose, wherein the absolute stereochemistry of this natural product was completely established by the modified Mosher analysis of a synthetic intermediate prepared through a separate route (Scheme 1) [19]. In this approach involving nucleophilic cyclization of acyclic aldehyde in situ generated from olefin 2 for constructing the piperidine ring system, proper synthetic manipulation of the three inherent stereocenters contained in the chiral source was a key strategy for ensuring effective stereocontrol to achieve completion of the target-directed synthesis. In addition to improvement of the inefficient stereoselectivity observed in allylation process from 4 to 7, we established the new alternative synthetic route to (+)-batzellaside B from L-pyroglutamic acid, which offers the advantages of convenience and simplicity of total synthesis

Results and Discussion

H H TBS TBS MOM MOM Ac Ac Ac Ac

Conclusion