Natural Product Synthesis via Biocatalysis: An Essay on the Merits of Multidisciplinary Ventures

Tomas Hudlicky

doi:10.1590/s0103-50531998000400003

Abstract

A critical opinion is advanced on the merits of multidisciplinary ventures in synthetic organic chemistry. In particular, the concept of a "tool box" of methodologies available for effective solutions to problems in organic synthesis is analyzed in the context of available examples from the literature as well as from the ongoing projects in our research group. The discussion of several cases of recently accomplished total syntheses offers evidence that the introduction of biocatalytic methods greatly improves the overall process of preparation of target compounds. Some examples of such projects form also the topic of the authors lecture at the 8th Brazilian Meeting on Organic Synthesis in September 1998.

Highlights

The total synthesis of natural products enjoyed fast growth during the 1960’s and the 1970’s, perhaps at the expense of more basic disciplines such as physical organic chemistry and methodology-oriented synthetic organic chemistry
In the 1980’s the emphasis returned to developmental organic chemistry. The reasons for such a paradigm shift are not entirely clear but there are several possible explanation: first, the trust in the synthetic community has been eroded because the promises of ‘‘practical solutions to the supply problem of therapeutically useful agents’’ have not materialized and no naturally occuring compound has been made by total synthesis in a manner competitive with isolation or fermentation methods
The recognition of enzymatic oxygenation of aromatics[10] as a ‘‘tool’’ to establish permanently the cis-diol features within the product leads to a four-step preparation of the target compound in a manner that would lend itself to a largescale synthesis if desirable[11]

Summary

Tomas Hudlicky

Apresenta-se uma opinião crítica a respeito dos méritos de atividades multidisciplinares contendo uma certa dose de ousadia, em química orgânica sintética. O conceito de ‘‘caixa-de-ferramentas’’das metodologias disponíveis para a solução eficaz de problemas em síntese orgânica é analisado no contexto de exempolos disponíveis na literatura, assim como a partir e projetos de pesquisas em andamento em nosso grupo de pesquisas. The discussion of several cases of recently accomplished total syntheses offers evidence that the introduction of biocatalytic methods greatly improves the overall process of preparation of target compounds. Some examples of such projects form the topic of the authors lecture at the 8th Brazilian Meeting on Organic Synthesis in September 1998

Introduction

Discussion

HO OR

OH OH O

Conclusion