Molecular shape is a presentation of a molecule’s three-dimensional structure and its volume of space and surface electrostatic potential map collectively define the function, e. g. as a modulator or probe to biological targets. Molecular shape diversity for compound libraries with multiple scaffolds (rich skeletal diversity) is recognized as a prerequisite for discovering broad bioactivity. Established strategies and methodologies for diversity-oriented synthesis (DOS) are useful for generating molecular shape diversity by synthesizing natural product-like compounds. On the other hand, diverted total synthesis (DTS) offers natural products and analogues with a higher degree of structural diversity and complexity. Examples of DOS of privileged heterocycles and DTS of amphidinolide T marine macrolides from the author’s laboratories are illustrated.
Laboratory of Advanced Catalysis and Synthesis, Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China / Laboratory of Asymmetric Catalysis and Synthesis, Department of Chemistry, Zhejiang University, Hangzhou 310027, China
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