A Comparative Study of Synthetic Approaches Towards Total Synthesis of Mandelalide A, An Anti-Lung Cancer Metabolite From Lissoclinum Ascidian

Author(s): Ghulam Shabir, Aamer Saeed*.

Journal Name: Current Organic Chemistry

Volume 22 , Issue 2 , 2018

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Abstract:

The aim of this review is to provide a detailed account of the total synthetic approaches toward glycosylated Macrolide A. Mandelaide A was isolated from Lissoclinum Ascidian species found in Algoa Bay, South Africa and has been reported to exhibit potent cytotoxicity against a human lung cancer and a mouse neuroblastoma cell line. We have summarized the maneuvers in each paper by graphically detailing the synthesis, and associated reaction niceties, of only the key intermediates prepared by each research group. Fascinating structural feature of mandelalide A is a 24-membered α,β-unsaturated macrolactone, which contains a conjugated diene, a trisubstituted tetrahydrofuran (THF) segment, and a trisubstituted tetrahydropyran (THP) moiety attached to an unusual carbohydrate unit, 2-O-methyl-α-L-rhamnose. The macrolide is decorated with twelve challenging stereocenters being the part of oxygen containing heterocyclic rings. The total synthesis of mandelalide A involves a variety of renowned reactions which include Prins cyclization for the diastereoselective construction of tetrahydropyran subunit, Rychnovsky-Bartlett cyclization for the diastereoselective construction of tetrahydrofuran moiety, construction of the tetrahydropyran segment, Suzuki coupling, Horner-Wadsworth-Emmons (HWE) macrocyclization, Shiina-type macrolactonization, Sonogashira cross-coupling, Silver catalyzed cyclizations, alkyne metathesis and glycosylation to append the L-rhamnose-derived pyranoside. This review provides a critical account along with a comparison of the synthetic efforts directed to this important natural product and its analogues.

Keywords: Total synthesis, Lissoclinum ascidian, macrolide A, macrolactonization, stereocenters, synthetic approaches, suzuki coupling.

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Article Details

VOLUME: 22
ISSUE: 2
Year: 2018
Page: [101 - 127]
Pages: 27
DOI: 10.2174/1385272821666170914112741
Price: $58

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