Girish Prabhu

Amino acid fluorides: viable tools for synthesis of peptides, peptidomimetics and enantiopure heterocycles

This review provides a broad perspective of the uses of amino acid fluorides in the synthesis of peptides and a wide range of other molecules. The topic is discussed with reference to the preparation of N-protected amino acid fluorides, their reactivity, coupling and their synthetic applications. The merits of the use of amino acid fluorides as coupling agents for making difficult peptides and in combating the problem of stereomutation, as well as their successful use in solid phase peptide synthesis, are reported with examples. Recent developments in the application of amino acid fluorides for making amino acid derivatives, peptide conjugates, peptide mimics and heterocycles are also reviewed.

Synthesis of chiral Nβ-protected amino diselenides from the corresponding amino alkyl iodides using NaBH2Se3 as a selenating reagent and their conversion to seleninic acids

A convenient approach has been presented for the synthesis of Nβ-protected amino diselenides from the corresponding amino alkyl iodides using in situ generated NaBH2Se3 as an efficient selenating reagent. All the diselenides are obtained in good yields under very mild conditions, short duration times and the protocol is free from racemization. The methodology has been effectively extended to the synthesis of N-protected L-selenocystine methyl ester. Clean oxidation of Nβ-protected amino diselenides to Nβ-protected amino seleninic acids using 35% aqueous H2O2 has also been accomplished. The present protocol is compatible with all the common urethane protecting groups.

Oxidative Amidation of Benzyl Alcohols with Amino Acid Esters Mediated by N-hydroxysuccinimide/phenyliodine Diacetate

ABSTRACT A simple protocol involving metal-free oxidative amidation of benzyl alcohols with amino acid esters has been presented. The amidation proceeds in a radical pathway unlike in conventional metal-mediated extrusion of dihydrogen. The method is advantageous in terms of metal-free conditions, nonexpensive commercial starting substrates. Also various substituents in the starting materials are tolerated and sterically hindered amino acid side chains could provide good yields of amide products. GRAPHICAL ABSTRACT

Design and Synthesis of a Novel N-(1H-tetrazol-5-yl)methyl Cyclic Peptoid Using Nosyl-protected N-(1-trityl-1H-tetrazol-5-yl)methyl Substituted Glycine

A solid phase synthesis of a cyclic peptoid bearing (1H-tetrazol-5-yl)methyl as N-substituent has been developed employing the monomer approach. The requisite monomeric Nosyl-protected N-(1-trityl-1H-tetrazol-5-yl)methyl substituted glycine was accessed by a convenient synthesis involving Click reaction of Nosyl-protected N-(cyanomethyl)glycine methyl ester and sodium azide as a key step. This building block was then employed in the solid phase synthesis of a tetramer peptoid. The linear tetramer was subjected to macrocyclization using PyBOP to obtain a cyclic peptoid with (1H-tetrazol-5-yl)methyl pendants in good yield.Graphical Abstract

Thionation of Di and Tripeptides Employing Thiourea as a Sulphur Transfer Reagent

A simple and efficient method for the synthesis of thiopeptides by the treatment of Nα-protected peptide esters employing DMF/PCl5 and thiourea as a sulphur transfer reagent is described. The conversion is carried out at room temperature within a short reaction time. The method is high yielding and free from racemization. Multiple thionation is demonstrated by conversion of two peptide bonds of tripeptides into thioamides. In addition, amino acid derived arylamides are also converted into aryl thioamides.

Synthesis of N-urethane protected amino alkyl (S-methyl)-isothiouronium compounds and carbodiimide tethered peptidomimetics: an application for guanidino and substituted guanidino peptidomimetics synthesis

The synthesis of N,N′-disubstituted and N,N′,N′′-trisubstituted guanidine linked peptidomimetic molecules suitably decorated in the peptide backbone has been delineated. Nα-Protected amino acid derived S-methyl isothiouronium derivatives are employed as the key intermediates for the synthesis of guanidinopeptide mimics. Synthesis of a new class of carbodiimide tethered dipeptidomimetics has also been outlined wherein a Staudinger-aza-Wittig type reaction between amino alkyl azide and isothiocyanato esters is employed. Thus obtained carbodiimides have been demonstrated as starting materials for the construction of guanidino peptide mimics as well as an array of trisubstituted guanidine mimetics bearing N-hydroxy, cyano and amino function as third substitutions at the guanidino unit in the backbone.

Facile one-pot synthesis of 2-amino-1,3,4-oxadiazole tethered peptidomimetics by molecular-iodine-mediated cyclodeselenization

Synthesis of 2-amino-1,3,4-oxadiazole tethered peptidomimetics is described by reaction of Nα-protected amino acid hydrazides with isoselenocyanato esters in one pot. The molecular-iodine-mediated cyclodeselenization of in situ generated selenosemicarbazide intermediates resulted in facile formation of 2-amino-1,3,4-oxadiazoles under mild conditions at excellent yields. The method employs environmentally benign iodine as the cyclizing agent and thereby avoids the harsh conditions employed in existing routes.

“Thioureidopeptide”: Novel Synthon for the Synthesis of N, N′, N″ -Trisubstituted Guanidinopeptide Mimics

The synthesis of Nα-protected N,N′,N″-trisubstituted guanidinopeptide mimic molecules suitably decorated in peptide backbone has been delineated in one pot employing HgCl2 as a desulphurizing agent. Chiral Nα-protected thioureidopeptide esters were employed as synthons for the synthesis of title molecules. The protocol is simple and the reaction conditions employed were mild, amenable to the amino acid chemistry.