New one-pot methodologies for the modification or synthesis of alkaloid scaffolds.

Amir E Wahba,Mark T Hamann

doi:10.3390/md8082395

Abstract

There are several avenues by which promising bioactive natural products can be produced in sufficient quantities to enable lead optimization and medicinal chemistry studies. The total synthesis of natural products is an important, but sometimes difficult, approach and requires the development of innovative synthetic methodologies to simplify the synthesis of complex molecules. Various classes of natural product alkaloids are both common and widely distributed in plants, bacteria, fungi, insects and marine organisms. This mini-review will discuss the scope, mechanistic insights and enantioselectivity aspects of selected examples of recently developed one-pot methods that have been published in 2009 for the synthesis of substituted piperidines, quinolizidines, pyrrolidines, hexahydropyrrolizines, octahydroindolizines and γ-lactams. In addition, progress on the synthesis of β-carboline (manzamine) alkaloids will also be discussed.

Highlights

The challenging task of developing a drug candidate from a natural source to clinical usage has many obstacles
Due to the growing interest in marine alkaloids, a detailed discussion of select, newly developed one-pot methodologies that have been utilized for the modification of marine alkaloids or the synthesis of common alkaloid moieties emphasizing asymmetric synthesis, are presented here
In this mini-review, we have highlighted a number of one-pot asymmetric methodologies developed for the synthesis of important alkaloid moieties

Summary

Introduction

The challenging task of developing a drug candidate from a natural source to clinical usage has many obstacles. Nature has been generous in providing structurally diverse molecules with varying biological activities, it is not always possible to obtain the required quantities of the desired drug candidate This lack of material has inspired innovative chemistry that develops new methodologies, catalysts and inventive synthetic routes for the synthesis and modification of natural products. Due to the growing interest in marine alkaloids, a detailed discussion of select, newly developed one-pot methodologies that have been utilized for the modification of marine alkaloids or the synthesis of common alkaloid moieties emphasizing asymmetric synthesis, are presented here This mini-review discusses applications, mechanistic insights and enantioselectivity of recently developed one-pot methods that have been published during 2009. This mini-review will cover our results for the manzamine alkaloids, as well as detailed asymmetric one-pot methods for the synthesis of substituted piperidines, quinolizidines, pyrrolidines, hexahydropyrrolizines, octahydroindolizines and γ-lactams

New One-Pot Methods Used in the Modification of Marine Alkaloids

One-pot asymmetric synthesis of substituted piperidines

One-pot organo-catalytic synthesis of quinolizidine derivatives

One-pot diastereoselective synthesis of γ-lactams

Findings

Conclusion