The sea conceals a mermaid’s grotto of useful chemicals-marine natural products of therapeutic potential. Marine sponges in particular are a rich source of natural products with structural diversity and novel biological activity. In recent times, there has been a growing interest in the synthesis of marine natural products. The present thesis entitled, “Synthesis of bioactive marine meroterpenoids: frondosins and liphagal” is an endeavor along the same lines and is organized under two parts –Part A and Part B.
Part A: Studies towards the total synthesis of (±) frondosins A and B
Frondosins A-E are IL-8 inhibiting marine meroterpenoids, with novel bicyclo[5.4.0]undecane framework, exhibiting anti-inflammatory and anti HIV-1 activities. A relatively simple and inherently flexible ring-closing metathesis (RCM) based strategy was employed to achieve the total synthesis of frondosins A (formal) and B in only 17 linear steps (total 13 operations) and 5% overall yield. A concise route, based on RCM, to the core structure of bioactive frondosins is amenable to ready appendage diversification and enables implementation of functionalization manoeuvres on all positions in the seven-membered ring of the bicyclic framework was also developed. A Diels-Alder strategy that led to the synthesis of 8-des-methyl norfrondosin A dimethyl ether is also delineated in Part A of the thesis.
Part B: A concise synthesis of (±) liphagal
Liphagal is a marine meroterpenoid displaying an unprecedented “liphagane” skeleton. It is a selective inhibitor of PI3K and significantly toxic against a small panel of human tumor cell lines (LoVo, CaCo-human colon and MDA-468-human breast). A concise and straightforward biomimetic strategy towards liphagal and its 14-des-formyl analogue that awarded liphagal dimethyl ether in only eight steps from commercially available building blocks is described in Part B of the thesis.
| Identifer | oai:union.ndltd.org:IISc/oai:etd.ncsi.iisc.ernet.in:2005/1993 |
| Date | 10 1900 |
| Creators | Shripad, Likhite Nachiket |
| Contributors | Mehta, Goverdhan |
| Source Sets | India Institute of Science |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
| Relation | G23511 |
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