Executive Summary : | Oxetanes are four-membered oxygen-containing non- aromatic heterocycles that are of great interest as new pharmaceutically potential pharmacophores with numerous biological activities. Oxetanes could be viewed as a gem-dimethyl equivalent, wherein the two methyl groups are bridged by an oxygen atom commonly been used in medicinal chemistry to block metabolically vulnerable methylene sites. The oxetane heterocycle has led to its incorporation as a pendant motif to improve "druglike" properties and also to offer intellectual property advantages. In addition to this oxetanes can be found in many natural products. Inspired by the biological and synthetic utility of oxygen and nitrogen based heterocycles such as oxetanes, azetanes/azetidines, isoxazolidines, isoxazolines, and cyclolignans and podophyllotoxin analogues in medicinal chemistry, herein we propose asymmetric intramolecular hydroxyl-directed nitrile oxide cycloaddition as an unprecedented approach for building these privileged scaffolds from inexpensive chiral sugar units such as glucose, glucal, galactal, mono and disubstituted 1,2-diols and 1,2-amino alcohols. • The advantage of the proposed hydroxyl directed nitril oxide cycloaddition is, regio and stereoselective and can generate three consecutive stereocenters in syn relationship. • The project's objective is to generate a library of novel heterocyclic scaffolds for their antibacterial activity evaluation because the proposed synthetic molecules structurally mimic the β-lactam antibiotics. • The present proposed work aims to replace conventional expensive metals catalyst, expensive starting materials, ligands and can lead to a smaller number of conversion steps to achieve oxetane and azetane skeletons with excellent stereoselectivity. • Further, the resulting oxetane-isoxazole heterocyclic compounds, bicyclic isoxazolidine, cyclolignans analogues scaffolds can also be functionalized and converted to various synthetic intermediates such as 1,3-amino alcohols, β-hydroxy carbonyls, 1,3-diols as required in the total synthesis of polyketide derived natural products. • The successful development of hydroxyl directed nitrile oxide cycloaddition reaction can open new avenue in the fields of oxetane and azetidines synthesis and their applications in drug discovery programmes related to β-lactam antibiotics and peptidomimetic science. It will serve as a potential tool in the discovery of oxetane-based chemotherapeutic agents. • Chemical biology investigations to find suitable candidates with optimal ADME properties will be executed in collaboration with Dr. Manoj Panchal, Central University of South Bihar, Department of Life Science, Bihar, Gaya. |