摘要:

1IntroductionThe often quotedraison d'êtrefor pursuing the total synthesis of natural products concerns the issue of “proof of structure.” Even now, with the ready availability of advanced analytical and spectroscopic techniques, structural revisions or assignments are made on the basis of synthetic undertakings. Pertinent examples which underscore this point which have appeared this year include the revised structures for antillatoxin1and tolyporphin A2and the assignment of absolute stereochemistry to (+)‐miyakolide3(Fig. 1). Application of basic chemical principles to biology at a molecular level is an ever increasing facet of the discipline: the consummate synthetic skills of leading groups such as those of Danishefsky4and Schreiber5being utilised in the synthesis of, for example, complex motifs for the investigation of molecular recognition events at cell surfaces and the detection of protein–ligand interactions. The synthesis of natural products on solid supports,6,7development of new methodologies8for “split‐pool synthesis”, synthesis of chemical libraries,9development of super high throughput screening procedures10and combinatorial approaches for catalyst development11are all underpinned by advances in chemical methodology, especially those in the area of carbon–carbon forming reactions.12The use of synthetic chemistry, in its broadest sense, for the preparation of composite materials13and highly functionalised nanostructural materials14was also much in evidence again this year. Given the rapid advancements in the field of combinatorial chemistry one might be forgiven if you thought that more traditional approaches to lead generation werepassé. However an intriguing article by Henkel,15which provides a comparative analysis of the structural complementarity between biologically active natural products and synthetic drug candidates, concludes by suggesting that nature will continue to provide a diverse variety of structural types for biological evaluation: a conclusion which is clearly validated by the isolation16of marine natural products such as the mycalolides. The isolation of natural products such as these will undoubtedly continue to provide leads for the pharmaceutical chemist and also present new methodological challenges for the synthetic chemist.

ISSN:0069-3030    

出版商:RSC    

年代:2000

数据来源: RSC