Balasubramanian Sridhar

Design, Synthesis, and Structure–Activity Correlations of Novel Dibenzo[b,d]furan, Dibenzo[b,d]thiophene, and N-Methylcarbazole Clubbed 1,2,3-Triazoles as Potent Inhibitors of Mycobacterium tuberculosis

A molecular hybridization approach is an emerging structural modification tool to design new molecules with improved pharmacophoric properties. In this study, 1,2,3-triazole-based Mycobacterium tuberculosis inhibitors and synthetic and natural product-based tricyclic (carbazole, dibenzo[b,d]furan, and dibenzo[b,d]thiophene) antimycobacterial agents were integrated in one molecular platform to prepare various novel clubbed 1,2,3-triazole hybrids using click chemistry. Structure-activity correlations and in vitro activity against M. tuberculosis strain H37Rv of new analogues revealed the order: dibenzo[b,d]thiophene > dibenzo[b,d]furan > 9-methyl-9H-carbazole series. Two of the most potent M. tuberculosis inhibitors 13h and 13q with MIC = 0.78 μg/mL (∼1.9 μM) displayed a low cytotoxicity and high selectivity index (50-255) against four different human cancer cell lines. These results together provided the potential importance of molecular hybridization and the development of triazole clubbed dibenzo[b,d]thiophene-based lead candidates to treat mycobacterial infections.

A Flexible Enantioselective Total Synthesis of Diospongins A and B and Their Enantiomers Using Catalytic Hetero-Diels-Alder/Rh-Catalyzed 1,4-Addition and Asymmetric Transfer Hydrogenation Reactions as Key Steps

A unified enantioselective route to total synthesis of diospongins A and B and their enantiomers has been developed employing achiral starting materials. All three stereocenters were introduced by means of catalytic reactions.

Relay Catalytic Branching Cascade: A Technique to Access Diverse Molecular Scaffolds

Tradition-ally, the molecules in these libraries have come from nature,and there are many examples in which natural products andtheir derivatives and analogues are either new drug candi-dates or tools for chemical biology and medicinal chemistryresearch.However,somedifficultiesareassociatedwithusingnatural products in screening experiments; for instance, theirpurification, the identification of biologically active compo-nents, and nature “fails” to provide several analogues, whichare necessary for structure–activity relationship (SAR) stud-ies. These restrictions make chemical synthesis the onlyalternative to obtain unambiguously characterized, diverse,multifunctionalmoleculesthataresimilartonaturalproducts.Diversity-oriented synthesis (DOS), a terminology ini-tially coined by Schreiber,

Gold(III) chloride-catalyzed three-component reaction: a facile synthesis of alkynyl derivatives of 1,2-dihydroquinolines and isoquinolines.

Gold(III) chloride is found to be an effective catalyst for the addition of alkynes on activated quinoline/isoquinolines to produce a series of alkynyl-substituted 1,2-dihydroquinolines and isoquinolines in a single-step operation. The easy availability of starting materials, convenient synthetic procedure, operational simplicity, and high regioselectivity makes this strategy very useful for the preparation of enyne derivatives of aza-aromatic compounds.

Pt(IV)-Catalyzed Hydroamination Triggered Cyclization: A Strategy to Fused Pyrrolo[1,2-a]quinoxalines, Indolo[1,2-a]quinoxalines, and Indolo[3,2-c]quinolines

A PtCl(4)-catalyzed hydroamination-triggered cyclization strategy to access biologically interesting N-containing heterocycles such as pyrrolo[1,2-a]quinoxalines, indolo[1,2-a]quinoxalines, and indolo[3,2-c]quinolines is described. The reaction makes use of aminoaromatics such as 1-(2-aminophenyl)pyrroles, N-(2-aminophenyl)indoles, 2-(2-aminophenyl)indoles, and alkynes having a tethered hydroxyl group. Mechanistically, the reaction is very appealing since it involves multiple catalytic cycles catalyzed by a single metal catalyst PtCl(4). We observed a remarkable enhancement of the rate when reactions were run under microwave-assisted conditions.

Gold- and Platinum-Catalyzed Formal Markownikoff’s Double Hydroamination of Alkynes: A Rapid Access to Tetrahydroquinazolinones and Angularly-Fused Analogues Thereof

A highly efficient gold(I)- and platinum(II)-catalyzed process for formal Markownikoffs double hydroamination of alkynes tethered with hydroxyl group has been developed. The method was shown to be applicable to a broad range of 2-aminobenzamides and alkynols leading to the formation of multiply substituted tetrahydroquinazolinones. Interestingly, when Pt(IV)Cl(4) catalyst was employed, cyclic angularly fused compound was obtained.

Versatile intramolecular aza-Prins and Prins cyclization of aryl epoxides: a facile synthesis of diaza-, oxa-aza-, and dioxa-bicycles.

Aryl epoxides undergo coupling smoothly with (E)-hex-3-ene-1,6-ditosylamide in the presence of 10 mol % p-TSA in 1,2-dichloroethane at 75 degrees C to produce the corresponding 1,5-ditosyl-octahydro-1H-pyrrolidino[3,2-c]pyridines in good yields with high trans-selectivity, whereas the coupling of (Z)-hex-3-ene-1,6-ditosylamide gave cis-fused octahydro-1H-pyrrolidino[3,2-c]pyridines predominantly. The use of readily available p-TSA makes this method simple, convenient, and practical.

Synthesis and characterization of 9,10-bis(2-phenyl-1,3,4-oxadiazole) derivatives of anthracene: Efficient n-type emitter for organic light-emitting diodes

With a general aim to make anthracene derivatives multifunctional (n-type emitter) and also study their suitability as electron transport layers for organic light emitting diodes (OLED), and with a more specific interest to understand the charge transport and packing pattern in the solid state due to the rotating side rings, we report the synthesis and characterization of six novel molecules (5–10) in which the 9 and 10 positions of anthracene have been directly substituted by phenyloxadiazole groups. We have carried out detailed studies of these molecules including photophysical, electrochemical, electroluminescent studies and solid state structure determination through crystallographic techniques. The electron affinity is very high, around 3.1–3.2 eV, and the ionization potential is around 5.9–6.0 eV, comparable to the more commonly used electron transport electroluminescent layer Alq3. The studies reveal that the new molecules being reported by us, in addition to the high thermal stability, are quite efficient in a two layer unoptimized device with the device structure ITO/α-NPD/5–10/LiF/Al and have an emission in pure green. They also show very high efficiency as electron transport layer in device structure ITO(120nm)/α-NPD(30nm)/Ir(ppy)3 doped CBP(35nm)/BCP(6nm)/5(28nm)/Al(150nm). From these studies we conclude that the anthracene derivatives also have considerable potential as multifunctional layers and as electron transport layers in OLED.

N4-tetradentate dicarboxyamidate/dipyridyl palladium complexes as robust catalysts for the Heck reaction of deactivated aryl chlorides.

Structurally well defined and thermally stable Pd(II) complexes, derived from N4-tetradentate dicarboxyamide/dipyridyl ligands, were evaluated as catalysts for the Heck reactions of deactivated aryl chlorides and olefins (see scheme). The concept of using an anionic carboxyamide as an ancillary ligand for palladium demonstrated here provides a new opportunity for the development of phosphine-free transition-metal catalysis.

Gold-Catalyzed Intramolecular Cyclization of N-Propargylic β-Enaminones for the Synthesis of 1,4-Oxazepine Derivatives.

An efficient and mild one-pot, gold-catalyzed intramolecular cyclization of N-propargylic β-enaminones has been achieved for the generation of 1,4-oxazepine derivatives. This synthetic transformation tolerates a range of substituted N-propargylic β-enaminones in moderate to good yields.