Subhash Ghosh

2,5-Anhydro sugar diacid and 2,5-anhydro sugar diamine based C2 symmetric peptidomimetics as potential HIV-1 protease inhibitors

Conformationally constrained molecular frameworks of the 2,5-anhydro sugar diacid (9) and 2,5-anhydro sugar diamines (10, 11) were used to construct architecturally beautiful novel C 2 symmetric peptidomimetics 1-8. Although none of these compounds showed any significant HIV-1 protease inhibitory activity, further refinements in design may lead to protease inhibitors based on these rigid carbohydrate-derived scaffolds.

Sugar‐Modified Foldamers as Conformationally Defined and Biologically Distinct Glycopeptide Mimics

It is predicted that over half of all eukaryotic proteins are glycosylated, and it is now well-established that co- and post-translational modification of proteins with glycans can have dramatic consequences on their folding, stability, and ultimately their function.[1] Considerable effort has thus been invested in delineating the impact of appended carbohydrates on the conformational preferences of proteins and peptides in solution and vice versa,[2] and also in understanding their interactions with their cognate receptors.[3] These endeavours are not straightforward, and success in rationalizing such processes has been possible only in a handful of well-studied cases.[4] Important insights into such questions have been gleaned from the study of glycoconjugate mimetics, whose interactions with cellular targets can impact a wide range of physiological phenomena, including fertilization, immune response, host–pathogen interactions, cell growth, and tumor metastasis.[1] However, attempts to successfully correlate biological functions of structurally well-defined glycopeptides with their secondary structures have been relatively sparse,[2–4] despite the importance of such targets in the quest for carbohydrate-based therapeutics.[5]

Formal Total Synthesis of (+)-Neopeltolide

This paper describes the formal total synthesis of (+)-neopeltolide, a cytotoxic macrolide isolated from the marine sponge Neopeltidae. The key features of the synthesis include an asymmetric Evans alkylation to fix the C9-methyl center, Jacobsen hydrolytic kinetic resolution of terminal epoxides followed by their regioselective opening to fix the stereocenters at the C11 and C13 positions, respectively, a Pd-catalyzed oxa-Michael reaction to construct the tetrahydropyran ring, and Yamaguchi macrolactonization to form the macrocyclic core of the molecule.

Studies directed towards the synthesis of stevastelins—a macrolactonization approach to stevastelin B

A synthetic approach towards the cyclic depsipeptide immunosuppressant stevastelin B, based on the stereoselective synthesis of its propionate-derived fatty acid segment 6 that was coupled with the tripeptide 7 leading to the advanced stage acyclic intermediate 5, is described. In spite of our best efforts, the crucial macrolactonization reaction was not successful.

Total Synthesis of the Proposed Structure of Maltepolide C

The first total synthesis of the proposed structure of cytotoxic macrolide maltepolide C has been achieved via an E-selective intramolecular Heck cyclization as a key step. Other key features of the synthesis are Z-selective Wittig olefination, Sharpless asymmetric dihydroxylation followed by Williamson-type cyclo-etherification, Brown asymmetric allylation, and Noyori reduction of an alkynone. Detailed NMR study confirms the structure and stereochemistry of the synthetic maltepolide C unambiguously. However, the deviation of the spectra of the synthetic maltepolide C from those of the natural maltepolide C indicates a possible error in the original structural assignment.