Total Synthesis of Naturally Occurring Dimeric Indolosesquiterpene Alkaloid: Dixiamycin C

Niyogi, Sovan (2024) Total Synthesis of Naturally Occurring Dimeric Indolosesquiterpene Alkaloid: Dixiamycin C. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (PhD thesis of Sovan Niyogi (19RS046)) 19RS046.pdf - Submitted Version Restricted to Repository staff only Download (31MB)

Abstract

Indolosesquiterpene alkaloids are composed of an architecturally intriguing pentacyclic framework with four contiguous stereogenic centres at the periphery of a trans-decalin scaffold embedded with carbazole unit. In 2010, xiamycin A (1a) and xiamycin A methyl ester (1b), displaying anti-HIV and antibiotic activities, were isolated by Hertweck et. al. from Streptomyces sp. GT2002/15032a and HKI0595, In 2012, the atropisomeric indolosesquiterpenoid natural products dixiamycins A and B were isolated independently by Zhang and Hertweck. Along with N-N dimer Hertweck and coworkers report a dixiamycin C (4). It is found that, the N-N and C-N dimeric forms of these antibacterial natural products are nearly an order of magnitude more potent than their monomeric siblings. As a part of my PhD program, we have envisioned an asymmetric strategy for the synthesis of indolosesquiterpene alkaloids that takes advantage of Corey’s polyene cyclization to install the required four contiguous stereo genic centres. Next, the trans-decalin core having an angular methyl group was elaborated to the monomeric unit of indolosequiterpenoid (xiamycin A methyl ester) in few steps. Finally, aromatic electrophilic bromination followed by a latestage oxidative C-N bond formation completed the total synthesis of dixiamycin C (4).

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