Ravi Sankar Ampapathi

Diversity oriented synthesis of pyran based polyfunctional stereogenic macrocyles and their conformational studies.

A new approach to synthesize a homologous series of 14-, 15-, and 16-membered drug-like, macrocyclic glycoconjugates involving TBAHS promoted azide-propenone intramolecular cycloaddition in designed C-glycopyranosyl butenones from a simple sugar d-glucose and d-mannose is reported.

One‐Pot Synthesis of Highly Fluorescent Pyrido[1,2‐a]indole Derivatives through CH/NH Activation: Photophysical Investigations and Application in Cell Imaging

We describe a straightforward strategy for the synthesis of strongly fluorescent pyridoindoles by Pd-catalyzed oxidative annulations of internal alkynes with C-3 functionalized indoles through CH/NH bond activation in a one-pot tandem process. Mechanistic investigations reveal the preferential activation of NH indole followed by CH activation during the cyclization process. Photophysical properties of pyridoindoles exhibited the highest fluorescence quantum yield of nearly 80 %, with emission color varying from blue to green to orange depending on the substructures. Quantum mechanical calculations provide insights into the observed photophysical properties. The strong fluorescence of the pyrido[1,2-a]indole derivative has been employed in subcellular imaging, which demonstrates its localization in the cell nucleus.

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]

Robust Turn Structures in α3β Cyclic Tetrapeptides Induced and Controlled by Carbo-β3 Amino Acid

Designing cyclic tetrapeptides (CTPs), which fold into desired structures, is often a challenging task. While it is difficult to synthesize them, they are also prone to adopt multiple conformations. In this paper we report the synthesis and conformational studies of CTP mimics, having nonconstrained α(3)β motif, that exhibit stable β- and γ-turn structures. We also demonstrate the transformation of β-turn to γ-turn structure in similar CTPs by inverting the chirality of β(3) carbon in C-linked-carbo-β(3)-amino acid (Caa) from R to S.

Metal-Free Decarboxylative Cyclization/Ring Expansion: Construction of Five-, Six-, and Seven-Membered Heterocycles from 2-Alkynyl Benzaldehydes and Cyclic Amino Acids.

A one pot synthesis of 1H-benzo[g]indoles, tetrahydrobenzo[h]quinolines, and naphtho[1,2-b]azepines from 2-alkynyl benzaldehydes and cyclic amino acids is reported. The salient feature of the strategy involves formation of three new bonds (one C-N and two C-C bonds) by a metal-free decarboxylation/cyclization/one-carbon ring expansion sequence in one pot.

Furan-Based Locked Z-Vinylogous γ-Amino Acid Stabilizing Protein α-Turn in Water-Soluble Cyclic α3γ Tetrapeptides

Described here is the design, synthesis, and conformational analysis of cyclic tetrapeptides (CTPs) with α3γ architecture containing a furan-based locked Z-vinylogous amino acid (Vaa). This unnatural amino acid locks into a γ-turn that induces type IαRS-turn in the CTPs. Stabilized by a 13-membered intramolecular H-bond, these CTPs show robust conformation in water and aprotic solvent irrespective of the sequence of tripeptide consisting of α-amino acids used.

Ti(III)-mediated radical cyclization of epoxy-β-aminoacrylate in the synthesis of the substituted pyrrolidine core of necine bases: synthesis of 2-epi-rosmarinecine

A radical-mediated approach to the necine base 2-epi-rosmarinecine is described. The synthesis is based on the stereoselective formation of a highly substituted pyrrolidine ring from β-aminoacrylate, diastereoselective allylation and intramolecular cyclization.

Influence of Linker Length on Conformational Preferences of Glycosylated Sugar Amino Acid Foldamers

Glycosylation of foldamers derived from furanoid sugar amino acids with mannose and a propyltriazole linker results in an unprecedented 16/10 mixed‐turn structure in the glycopeptides in water, with a preference for the higher‐order structure irrespective of the stereochemistry of the starting foldamer. This is in stark contrast to the structures displayed by the same oligomers in water when mannosylated with a two‐carbon‐shorter methyltriazole linker: 16‐membered turn structure in the cis‐foldamer and 10‐membered in its trans congener. This demonstrates the defining influence of the linker length on the structural preference of these novel glycopeptide mimics.

Diastereoselective Synthesis of 5-Heteroaryl-Substituted Prolines Useful for Controlling Peptide-Bond Geometry.

A versatile diastereoselective Friedel-Crafts alkylation reaction of heteroaryl systems with a cyclic enecarbamate for the preparation of 5-heteroaryl-substituted proline analogues in good yields has been developed. These heterocyclic tethered cyclic amino acid building blocks constitute important structural motifs in many biologically active molecules. The impact of the substitution on proline cis/trans isomerization was explored by carrying out solution conformational studies by NMR on 5-furanyl-substituted proline-containing peptides. Conformational analysis revealed that the peptide bond is constrained in an exclusively trans conformation.

Recent Studies on Gramicidin S Analog Structure and Antimicrobial Activity

Gramicidin S, the most notable example of cationic antimicrobial peptides (CAPs), has remained in the forefront of worldwide research for development of new antibiotics for over seven decades now. Hundreds of papers have been published over the years on this molecule and its numerous analogs, delineating their structures and biological activities with an aim to achieve selective antimicrobial activities with reduced cytotoxicity for potential therapeutic applications. The present review attempts to capture the essence of some of the recent studies with the aims to chronicle the journey traversed by this fascinating molecule so far and to decipher what is needed for future success.