Dynamic Aspects Of Natural Products Chemistry

Preface:

Natural products chemistry has a long history, and could be regarded as having its roots in the use of many kinds of herbal mixtures as crude drugs in traditional medicine. Systems of traditional medicine have been practiced in China and Japan for thousands of years, and virtually all regions of the world have used natural materials to treat human disease. It was clear that many plants, herbs, etc. contain components with powerful biological activities. The dawn of modern natural products chemistry began with the isolation of the active component, morphine, from opium. Subsequently, various alkaloids were isolated from medicinal plants and employed clinically. The discovery and the development of penicillin as a microbial metabolite opened up the era of antibiotics, which have saved countless lives in the past half century or so. The isolation and synthesis of steroid hormones resulted in the development of new concepts in molecular stereochemistry and organic synthetic techniques, as did the discovery of bioactive lipids such as prostaglandins and leukatrienes, bioactive peptides such as enkephalins and endetherines, and oligosaccharides, including glycoproteins. Further, the discovery of plant hormones has led to great strides in plant biotechnology, including plant tissue cultures, and derivatives of insect hormones and pheromones are now used as pesticides. Thus, applications of natural products chemistry have become all-pervasive in modern society.

Apart from the extensive practical applications of natural products and their derivatives, natural products chemistry has played a central role in the development of modern organic chemistry as a result of its focus on structural and synthetic studies of often highly complex and inaccessible molecules. Biosynthetic studies have also attracted much attention, aiming to answer the questions of why and how such a large number and variety of compounds are synthesised by organisms. Researchers in the field of biosynthesis first focused on elucidation of the pathways of secondary metabolism, and then on the mechanisms, of the enzymes catalyzing the biosynthetic reactions. This was an extremely difficult task, because rather large amounts of enzymes are required for the investigation of reaction mechanisms and the enzyme proteins are often unstable and not easy to purify. However, in recent years the development of molecular biology has made gene and protein engineering rather routine. Thus, studies of mechanistic enzymology can now be conducted with cloned and overexpressed enzyme proteins. It has been shown that the enzymes responsible for the biosynthesis of antibiotics in Streptomyces spp. are encoded in gene clusters. Further, cloning and functional analysis of the genes associated with flavonoid biosynthesis should soon cast light on the interesting question of why flavonoids are ubiquitously present in plant leaves.

Life is maintained not only by large molecules such as proteins and nucleic acids, but also by many small molecules which have essential and diverse roles in the physiology of living organisms. Such compounds often have highly specific interactions with target receptors, but the mechanisms involved largely remain to be explored. Current methodology means that this task can be addressed, and this in turn should lead to a host of new applications for natural products and their derivatives. The key may be an interdisciplinary approach taking account of both biological function and molecular behaviour based on precise structure recognition. As we increasingly understand the mechanisms of molecular recognition that operate in nature, many possibilities should open up for artificial control or modification of biological functions, as well as new challenges for synthetic organic chemists.

Our intention in this book is to focus on such dynamic aspects of natural products chemistry. By dealing in detail with representative topics to which the most modern techniques of research have been applied, we hope to emphasize the value of combining traditional approaches to natural products chemists with current biochemical and molecular-biological ideas. Each chapter provides sufficient background information and experimental detail to make the subject accessible to non-specialists. It is our hope that these examples of recent progress in key areas of natural products chemistry will stimulate work in related topics by illustrating the power of a modern interdisciplinary approach to the subject.