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Title: Towards the total synthesis of nakadomarin A
Author: Xu, Chao
ISNI:       0000 0004 5372 9831
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2015
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Nakadomarin A was first isolated from the sponge Amphimedon sp. by Kobayashi and co-workers in 1997. The structure showed a unique hexacyclic skeleton consisting of 5-, 6-, 8- and 13-membered rings. This natural product shows cytotoxicity, antimicrobial and inhibitory activities. The challenging structure, as well as the promising biological activity and limited availability make nakadomarin A an attractive target for total synthesis. The aim of the project was to design a synthesis of a common late-stage intermediate that could be used to prepare not only nakadomarin A, but also other members of the manzamine natural product family. The concise preparation of the common intermediate ABCD tetracyclic core was achieved in only 7 steps (longest linear sequence). The key features of the synthetic route are asymmetric construction of the AB ring using an asymmetric Pauson-Khand reaction; installation of the azocine D ring through metathesis reactions (CM, RCM) and Overman rearrangement; and introduction of the C ring by N-alkylation. Finally, several side chains were prepared and evaluated to find the optimum method for installation of the furan. This resulted in two advanced intermediates which could be malipulated to form nakadomarin A in only 3 steps.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QD Chemistry