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Total Synthesis of Hybrid Polyketide-Cyclic Peptide based Bioactive Natural Products and Analogues Thereof

Implementing Organization

Indian Association For The Cultivation Of Science, West Bengal
Principal Investigator
Prof. Rajib Kumar Gowsami
Department of Condensed Matter Physics and Materials Science, SN Bose Natioanl Centre for Basic Sciences, Kolkata, West Bengal, 700098
Indian Association For The Cultivation Of Science

Project Overview

Macrocyclic natural products, such as nemamides A-B, euglenatides A-E, koshidacins A-B, and enamidonins B-C, have gained attention due to their novel architectures and promising bioactivities. These members exhibit promising bioactivities, but some remain undetermined due to material scarcity. To understand their biological significance, efficient synthetic routes for chemical synthesis are needed. The proposed project aims to develop efficient synthetic routes to access targeted natural products in sufficient quantity and their variety of new analogues. Strategies for achieving unnatural β-amino acids bearing multiple chiral centers will be developed using Prins cyclisation followed by Ritter reaction sequence, while Sharpless asymmetric dihydroxylation will be tested for making unnatural amino acid 4,5-dihydroxynorvaline. The site for effective macrolactamization will be determined to obtain the required cyclic peptides, which will be stitched together with polyketide counterparts using a Heck coupling-based late-stage functionalization approach. The proposed structures of the natural products will be validated, and the unassigned stereocenter present in euglenatide C will be determined. Different chemical reactions will be tested to construct the required polypropionate parts of the targeted molecules and their different analogues. Bicyclic analogues of some targeted natural products will be prepared to explore their biological implications. All synthesized molecules will be screened for anticancer, antifungal, and antibacterial activities to find possible leads for future development.
Funding Organization
Funding Organization
Science and Engineering Research Board (SERB), New Delhi
Anusandhan National Research Foundation (ANRF)
Quick Information
Area of Research
Chemical Sciences
Focus Area
Natural Product Synthesis, Medicinal Chemistry
Start Year
2024
End Year
2027
Sanction Amount
₹ 47.74 L
Status
Ongoing
Output
No. of Research Paper
00
Technologies (If Any)
00
No. of PhD Produced
N/A
Startup (If Any)
00
No. of Patents
Filed :00
Grant :00
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