Perspectives from nearly five decades of total synthesis of natural products and their analogues for biology and medicine

• Published in: Natural product reports 2020-11, Vol.37 (11), p.144-1435
• Main Authors: Nicolaou, K. C, Rigol, Stephan
• Format: Article
• Language: English
• Subjects: Biological Products - chemical synthesis; Biological Products - chemistry; Biological Products - pharmacology; Drug Discovery; Molecular Structure
• ISSN: 0265-0568; 1460-4752
• DOI: 10.1039/d0np00003e

Covering: 1970 to 2020 By definition total synthesis is the art and science of making the molecules of living Nature in the laboratory, and by extension, their analogues. Although obvious, its application to the synthesis of molecules for biology and medicine was not always the purpose of total synthesis. In recent years, however, the field has acquired momentum as its power to reach higher molecular complexity and diversity is increasing, and as the demand for rare bioactive natural products and their analogues is expanding due to their recognised potential to facilitate biology and drug discovery and development. Today this component of total synthesis endeavors is considered highly desirable, and could be part of interdisciplinary academic and/or industrial partnerships, providing further inspiration and momentum to the field. In this review we provide a brief historical background of the emergence of the field of total synthesis as it relates to making molecules for biology and medicine. We then discuss specific examples of this practice from our laboratories as they developed over the years. The review ends with a conclusion and future perspectives for natural products chemistry and its applications to biology and medicine and other added-value contributions to science and society. This review article summarises a series of total syntheses of natural and designed molecules primarily for biology and medicine. Aspects of new synthetic strategies and methods and optimisation of biological properties are emphasised.