Quest for Target and Diversity Oriented Synthesis of Medicinally Important Natural Product and Natural Product-like Molecules from Amino Acids

Abstract

A major part of the drugs present in the market is natural products or natural productderived. The two main synthetic devices towards the drug development are Targetoriented synthesis (TOS) and Diversity-oriented synthesis (DOS) for creating structurally diverse compounds that cover the pharmaceutically relevant chemical space in an optimal way. On the other hand, an over-proportionally large number of drugs or lead structures also originate from compounds isolated from natural sources. So, the development of new synthetic routes for the natural products cannot be denied. Towards this perspective, the use of naturally occurring amino acids is well known because of their easy availability in chirally pure form. Again, they have at least two functional groups (amino and carboxylic acid groups) and by chemical transformations of these, they can be renovated to a broad range of biologically important compounds. The thesis entitled “Quest for Target and Diversity Oriented Synthesis of Medicinally Important Natural Product and Natural Product-like Molecules from Amino Acids” describes the synthesis of chiral heterocycles, bioactive natural products and related diversity from natural amino acids as the chiral synthones. The present investigations have been carried out by the author under the supervision of Dr. Gautam Panda, Medicinal and Process Chemistry Division, CSIRCentral Drug Research Institute, Lucknow 226031, UP, India. The work embodied in this thesis has been organized under six chapters: Chapter 1: In ‘Chapter 1’ a brief review on synthesis of Natural Products having antitubercular activity has been described. Chapter 2.1: Unprecedented formation of benzo[d][1,2,3,6]oxatriazocine derivatives via diazo-oxygen bond formation and synthesis of enantiomerically pure 1-alkyl benzotriazole derivatives In ‘Chapter 2 Part-A’ a series of amino acid-derived enantiomerically pure substituted benzo[d][1,2,3,6]oxatriazocine derivatives has been prepared by the diazotization of amino acid-derived benzo-fused alicycles via one-pot three step sequences, (i) diazotisation (ii) TBDMS deprotection, and (iii) cyclization. Chapter 2.2: Trifluoroacetic Acid-Catalyzed Domino Reaction for Amino Acids Derived 2,3-Dihydro-1H-1,5-benzodiazepines