A Case for Bond‐Network Analysis in the Synthesis of Bridged Polycyclic Complex Molecules: Hetidine and Hetisine Diterpenoid Alkaloids. Issue 27 (15th April 2020)

• Record Type: Journal Article
• Authors: Doering, Nicolle A.; Sarpong, Richmond; Hoffmann, Reinhard W.
• Is Part Of: Angewandte Chemie international edition. Volume 59:Issue 27(2020)
• Page Start: 10722
• Page End: 10731
• Publication Date: 2020-04-15
• Subjects: alkaloids -- polycycles -- synthesis design -- terpenoids -- total synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201909656
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: A key challenge in the synthesis of diterpenoid alkaloids lies in identifying strategies that rapidly construct their multiply bridged polycyclic skeletons. Existing approaches to these structurally intricate secondary metabolites are discussed in the context of a "bond‐network analysis" of molecular frameworks, which was originally devised by Corey some 40 years ago. The retrosynthesis plans that emerge from a topological analysis of the highly bridged frameworks of the diterpenoid alkaloids are discussed in the context of eight recent syntheses of hetidine and hetisine natural products and their derivatives. This Minireview highlights the extent to which network analyses of the type described here sufficed for designing synthesis plans, as well as areas where they had to be amalgamated with functional group oriented synthetic planning considerations. Abstract : A key challenge in the synthesis of diterpenoid alkaloids lies in identifying efficient strategies to construct their multiply bridged polycyclic skeletons. Approaches from eight recent syntheses are discussed in the context of "bond‐network analyses", highlighting the efficacy of bond‐network analyses for synthesis planning, as well as where other considerations had to be incorporated.