Indrapal Singh Aidhen

The glycosylated chalcones are being revisited as promising chemical scaffolds in medicinal chemistry because of their improved bioavailability compared to aglycone chalcones. This article briefly highlights the natural O- and C-glycosylated chalcones present in literature and presents the summary of our recent synthesis of C-glucosylated isoliquiritigenin, a C-glucosylated chalcone with promising aldose reductase inhibition properties.

A new reagent for the synthesis of the α,β-unsaturated N-methoxy-N-methyl-amide structural unit has been developed. 2-(Benzo[d]thiazol-2-ylsulfonyl)-N-methoxy-N-methylacetamide, a crystalline solid with an indefinite shelf life that can be easily prepared in two convenient steps from 2-chloro-N-methoxy-N-methylacetamide, reacted with a variety of aldehydes under Julia conditions to furnish the α,β- unsaturated N-methoxy-N-methyl-amide functionality. © Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

A series of threo- and erythro-configured open-chain trihydroxy ketones was synthesized starting from L- and D-ascorbic acid respectively as the starting material, through the use of Grignard reactions for the requisite C[sbnd]C bond formations. The lipophilic ketones were screened against Mycobacteriumtuberculosis for anti-proliferative activity. The lipophilic ketones with tetradecyl alkyl side chains were found to be moderately active against cell proliferation.

Bifunctional synthetic equivalents containing a Weinreb amide as one of the functionalities have been synthesized from commercially available o-, m-, and p-toluic acid. These bifunctional building blocks enabled efficient C-C bond formation through Wittig reaction with simple and functionalized aldehydes on one hand and a clean nucleophilic addition of 3,4,5-trimethoxy phenylmagnesium bromide onto the Weinreb amide functionality on the other hand, therebypaving way for an efficient and convenient synthesis of novel analogues of phenstatin with highly functionalized appendages. Further addition of various aryl or heteroarylmagnesium bromides onto theWeinreb amide functionality provided a general strategy for synthesizing unsymmetrical diaryl ketones conjugated to a monosaccharide moiety for the first time. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A new strategy for the synthesis of 3-arylisocoumarins and 8-hydroxy-3-arylisocoumarins was investigated by using acyl anion chemistry for the initial C–C bond formation. The obtained keto esters and keto lactones as intermediates underwent based-promoted intramolecular cyclization to afford 3-arylisocoumarins in good yields. The developed methodology was applied for the synthesis of the important natural products thunberginol A and cajanolactone A.

A successful strategy based on the synthetic equivalent containing Weinreb amide functionality for the convenient access to 1,1-diarylethenes in general and for the isocombretastatin analogues in particular has been developed from the commercially available glyoxalic acid. The convenience with which the structural variations can be made in assembling the aryl residues shows generality associated with the developed strategy. The intermediates also provide access to 1,2,2-triarylethanones, represented by the synthesis of advanced intermediate of tamoxifen. © 2011 Elsevier Ltd. All rights reserved.

This study evaluated four donor-π-linker-acceptor (D-π-A) dyes experimentally, which either have 1 or 3 triphenylamine (TPA) donor in combination with either pyridine or N-methyl pyridinium ion as acceptor. In this study, by increasing the number of closely spaced HOMOs (by way of adding multiple TPA to the acceptor), the fraction of visible spectrum that was absorbed increased. Through the density functional theory calculations and the relevant experiments, the number of closely spaced HOMOs was shown to be directly proportional to the number of TPA moieties in the dye. N-methyl pyridinium based dyes have shown lesser band gap (2.2-2.5 eV) when compared to its pyridine based counterpart (3.08-3.3 eV) due to its high electron withdrawing nature. Hence, an octupolar dye, 2,4,6-tris((E)-4-(diphenylamino)styryl)-1-methylpyridinium iodide, containing three TPA donors and N-methyl pyridinium ion acceptor was identified as effective light harvesting dye for dye-sensitized solar cells application.

Lack of B0AT1 (SLC6A19) partially protects mice against the onset of non-alcoholic steatohepatitis (NASH). To achieve a similar outcome through pharmacological treatment, we improved previously identified inhibitors of B0AT1 by medicinal chemistry and identified second generation inhibitors by high through-put screening. Modified diarylmethine compounds inhibited B0AT1 with IC50 values ranging from 8–90 μM. A second generation of inhibitors was derived from high-throughput screening and showed higher affinity (IC50 of 1–15 μM) and strong selectivity against amino acid transporters with similar substrate specificity, such as ASCT2 (SLC1A5) and LAT1 (SLC7A5). All compounds were unrelated to B0AT1 substrates, but were likely to bind in the vicinity of the substrate binding site.

A new route based on the use of acyl anion chemistry was developed for the synthesis of (+)-centrolobine and its analogues. Acid-catalyzed benzylic cation initiated cyclization was the key step in the stereoselective formation of the cis-2,6-disubstituted tetrahydropyran ring. The developed methodology was applied to the synthesis of (+)-centrolobine analogues containing electron-donating substituents in the aryl rings. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Two new Weinreb amide based bifunctional building blocks have been developed starting from meta and ortho-toluic acid for convenient access to meta- and ortho- positional isomers of FTY720. Julia olefination and Grignard reaction are the key steps used in the synthesis of 2 and 3. The bifunctional building blocks 4 and 5 are easy to scale-up and in addition to synthesis of 2 and 3, these building blocks would be valuable in search of a new amphiphiles, as the functionalities therein allows for change in the nature of polar head-group and lipophilic chain.