Kiran Bajaj

Quinine bis-conjugates with quinolone antibiotics and peptides: synthesis and antimalarial bioassay

Benzotriazole-mediated syntheses led to novel bis-conjugates of quinine with quinolone antibiotics and amino acid linkers which were successfully prepared by two alternative routes with excellent yields and retention of chirality. These bis conjugates retain in vitro antimalarial activity with IC(50) values ranging from 12 to 207 nM, similar to quinine itself.

Study of Chemical Ligation Via 17-, 18- and 19-Membered Cyclic Transition States

Unprotected S‐acylated cysteine isopeptides containing α‐, β‐ or γ‐amino acid units have been synthesized, and their conversion to native hexapeptides by S‐ to the N‐terminus ligations involving 17‐, 18‐ and 19‐membered cyclic transition states have been demonstrated both experimentally and computationally to be more favorable than intermolecular cross‐ligations.

Synthesis of some newer derivatives of 2-amino benzoic acid as potent anti-inflammatory and analgesic agents.

Diazotization of N-benzylidene anthranilic acids 1a-1n at pH 9 yielded N-[alpha-(phenylazo) benzylidene] anthranilic acids 2a-2n and at pH 3 yielded N-benzylidene-5-(phenylazo) anthranilic acids 3a-3n. When compounds 3a-3n were treated with thioglycolic/thiolactic acid in the presence of anhydrous ZnCl(2), 2-(4-oxo-2-phenylthiazolidin-3-yl)-5-(phenylazo) benzoic acids 4a-4n were afforded. The newly synthesized compounds were screened for their anti-inflammatory and analgesic activities and were compared with standard drugs, aspirin and phenylbutazone. Out of the compounds studied, the most active compound 4n showed more potent activity than the standard drugs at all doses tested.

Efficient Syntheses of Thiadiazole Peptides

Novel N-(Cbz-aminoacyl)thiosemicarbazides 3a-c were cyclized by treatment with sulfuric acid to give 1,3,4-thiadiazoles 4a-c. Compounds 4a-c reacted with N-(Cbz-aminoacyl)- and -dipeptidoylbenzotriazoles to afford chirally pure 1,3,4-thiadiazol-2-yl-substituted amino acids 6a-c and dipeptides 7a-c.

Syntheses of Chiral N‐(Protected) Tri‐ and Tetrapeptide Conjugates

Cbz‐(protected)‐tri‐ and tetrapeptide conjugates with steroids, sugars, terpenes, and heterocycles were prepared using Cbz‐(protected)‐tri‐ and tetrapeptidoylbenzotriazoles as active intermediates.

Amino acyl conjugates of nitrogen heterocycles as potential pharmacophores.

2-Methyl- and 4-methylpyridine and 2-methylquinoline are converted by benzotriazole-activated (Cbz)-protected amino acids into chiral potential novel pharmacophore aminoacyl conjugates (33-53%).

Microwave-Assisted Synthesis of Benzo-fused Seven-membered Azaheterocycles

The use of microwave energy in chemical reactions has revolutionized the field of heterocyclic chemistry in the past two decades. Synergy of microwave methodology with reactions performed on support media and/or in the absence of solvent constitutes an environmentally clean technique, which offers tremendous advantages such as clean chemistry, reduction in reaction times, improved yields, and applicability to wide range of reactions, safety and tremendous scope for automation over the traditional heating. The benzoannulated azaheterocycles display an impressive repertoire of biological activities. The present review will provide an in-depth view of microwave-assisted preparation of benzo-fused seven- membered azaheterocycles such as benzodiazepines, benzothiazepines and benzoxazepines.

Introduction of histidine units using benzotriazolide activation

Nα‐Boc‐Nim‐(4‐toluenesulfonyl‐l‐histidylbenzotriazole) enables convenient acylation of N‐, O‐, S‐, and C‐nucleophiles with no detectable racemization. We report efficient syntheses of novel histidine‐containing di‐, tri‐, and tetra‐peptides and models for the preparation of potentially biologically active histidine N‐, O‐, S‐, and C‐conjugates. Copyright

Aziridine-Mediated Ligation at Phenylalanine and Tryptophan Sites

An efficient approach towards peptide synthesis that allows easy access to variety of small peptides via one-pot aziridine-mediated ligation/desulfurization strategy has been described. The protocol afforded a library of phenylalanine- and tryptophan-containing α-peptides in good yields by regioselective ring-opening of aziridine-3-aryl-2-carboxylates with peptide thioacids, followed by desulfurization.

Traceless reductive ligation at a tryptophan site: a facile access to β-hydroxytryptophan appended peptides

An efficient methodology for cysteine-free ligation at a tryptophan (Trp) site is described. A chemically active scaffold, β-hydroxy-α-azidotryptophan, has been synthesized and explored towards the synthesis of a series of β-hydroxytryptophan appended native peptides in good yields via one-pot reductive traceless ligation of β-O-peptidyl-α-azidotryptophan involving an O → N peptidyl transfer strategy. Pre-organized conformational analysis and reaction energy pathway based theoretical studies further supported the experimental findings on the chemical structure stability of ligated products.