Total synthesis of drug and drug intermediates
Process development of a broad spectrum of structurally different types of drugs such as adriamycin, ambroxol hydrochloride, carbamazepine, calanolide A, combretastatin A-4, cloxacillin sodium, ciprofloxacin, dapsone, efavirenz, halofantrine, loperamide, mebendazole, olanzapine, roflumilast, taxol, tenidap sodium, tolnaftate, voriconazole, zolpidem and prostaglandins viz. PGE2, PGF2α, carboprost, misoprostol, latanoprost. Special skills are required in the synthesis of many of the drugs listed.
Some of the intermediates included benzimidazolone, 4-hydroxy-cyclo pentenone derivatives, caronaldehyde, cyclopropylamine, chlorofluro- anilines, halogenated alkyls and aryls, 2-methyl cysteine (synthon for thalessemia drug Desferrithiocin), methyl benzoylformate, furanone derivative, thiophene derivatives, 2-Benzylidene-tetralone analogues etc. in addition to the intermediates in the total synthesis of drugs listed above.
Total synthesis of natural products
New routes developed for the synthesis of duryne, microminutin, monocillins,
Patulolide A, podophyllotoxin and its analogues, daunomycin, dibromo –tyrosine derivatives (marine natural products), macrolide antibiotics such as recefieolide, mutisianthol,thia-Calanolide A (synthetic analogue)and solafuranone etc.
Drug Discovery Programme
Several analogues were designed and synthesized, chief among are for anticancer substances like 2,3-diaryl 4/5-hydroxycyclopentenone (~200 NCEs as combretastatin A-4 analogues), antifungal analogues of fluconazole, voriconazole and furanone derivatives (75 NCEs), and anti-HIV substances belonging to the NNRTI class of activity like aza-Calanolide A, and thia-calanolide A.
A library of compounds (14 nos.) belonging to the dibromotyrosine class (incorporating triazine groups) were synthesized using solid phase and liquid phase synthesis.
Development of synthetic methodologies
Expertise in synthesis and characterization of a number of homogeneous and heterogeneous catalysts and ligands with metals like Rhodium, Ruthenium, Palladium, Manganese, Nickel, Copper etc and their applications in important organic transformations like asymmetric aziridnation, cyclopropanation, epoxidations, asymmetric Heck reactions etc.
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Green chemical transformations
- Biotransformation reactions, application of ionic liquids and heterogeneous catalysts, were successfully demonstrated.
- Enzymatic ketone reduction, hydroxylation of steroids, trans- esterification, and lipase mediated resolution were developed.
- Aziridination, cyclopropanation, epoxidation, asymmetric Heck reaction, thioacetalization of carbonyl function, transthioacetalization of acetals, ketals, oximes and Hydrazones catalyzed by Natural clay.
- Microwave promoted solvent-free one-pot synthesis of N,N’-disubstituted urea derivatives.
- Selective oxidation of Benzylic alcohols to the corresponding carbonyl compounds with TBHP over Cr.S-2,
- Efficient selective regeneration of carboxylic acids from their corresponding allyl or cinnamyl esters using Natural Kaolinitic Clay and EPZG.
- Heck reaction using Pd-Cu exchanged K10 clay and Pd impregnated hydrotalcite represent some of the green methods developed.
- Solvent free selective silylation of alcohols, phenols and Naphthols with HMDS Catalyzed by H-b Zeolite.
- Mild and facile procedure for clay catalyzed acetonide protection and deprotection of N(Boc)-amino alcohols and protection of 1,2-Diols.
- Resolution of phenethyl alcohol by tran-esterification using enzymes like Lipases, Candida species, pseudomonas species etc. in the presence of ionic liquids.
- Microwave and ultra-sonography promoted aziridnation.
- Applications of phosphorous based ionic liquids in nitration of phenols.
- Green synthesis of coumarins using chromium silacalites, quinolinones using hydrotalcites, selective hydroxylation of phenols using titanium
silicalite, H-β zeolite-catalysed aziridnation etc. H-Y catalysed transesterification of β-keto esters.
- Heck reaction catalysed by Pd, Mn, Ni based hydrotalcites.
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