Namakkal G. Ramesh

Iodine catalyzed one-pot diamination of glycals with chloramine-T: a new approach to 2-amino-β-glycosylamines for applications in N-glycopeptide synthesis

Iodine catalyzes a facile one-pot direct diamination of glycals with chloramine-T to afford stereoselectively 2-amino-beta-glycosylamine derivatives that serve as convenient precursors for the synthesis of N-linked glycopeptides.

A versatile strategy for the synthesis of N-linked glycoamino acids from glycals.

A versatile route for the synthesis of N-linked glycoamino acids from readily available glycals is reported. A variety of glycals possessing different carbohydrate templates (mono-, di- and trisaccharide glycals) were shown to undergo a novel iodine catalyzed stereoselective diamination reaction with chloramine-T. Taking advantage of the difference in the reactivity between the anomeric and C2 sulfonamido groups of these diamines 7, 13, 15, 17 and 19, they could be protected differentially at the C2 and anomeric nitrogen atoms. Thus, chemoselective acetylation of these diamines installed the C2 acetamido group, an essential functionality that plays a crucial role in inducing a beta-turn in N-linked glycoproteins. Subsequent protection of the anomeric nitrogens of 20a,b,e as their Alloc (allyloxycarbonyl) derivatives followed by SmI(2) mediated facile didetosylation afforded 24a-c. Deprotection of the Alloc group of 24a and 24c and coupling of the liberated free amine with a variety of protected amino acids provided N-linked glycoamino acids 25 and 27 in high yields. An illustrative synthesis of an N-linked glycopeptide 29 is also reported.

Asymmetric synthesis of substituted cyclopentanes via Michael initiated ring closure reactions

Abstract Michael initiated ring closure reactions of bromosulfone 1 and γ-oxygenated (E)-α,β-unsaturated esters, which lead stereohomogeneously to trisubstituted methylenecylopentanes, proceed also with good facial selectivity. The use of nonracemic enoate 1 4 in these reactions led to the synethesis of enantiomerically pure cylcopentanone 1 7 . The reason for the preferred anti -selective. Michael addition of enoate 1 4 with allyl and alkyl α-phenylsulfonyl lithiated reagents is discussed.

Design and synthesis of new amino-modified iminocyclitols: selective inhibitors of α-galactosidase

A new and short synthesis of hitherto unreported stereo analogue of amino-modified five-membered iminocyclitols from readily available tri-O-benzyl-D-glucal is described. Significantly, glycosidase inhibition studies of alkylamino substituted iminocyclitols display a high degree of selectivity towards alpha-galactosidase.

Amino-functionalized iminocyclitols: synthetic glycomimetics of medicinal interest

Carbohydrate mimetics play vital roles in various cell-mediated processes due to their structural resemblance to natural sugars but properties quite distinct from them. This unique combination has made them attractive targets for synthesis, exploring their biological applications, and understanding their structure–activity relationship at molecular levels, that would eventually help in the development of novel small molecule drugs. Iminosugars, also termed iminocyclitols and, often erroneously azasugars, constitute the most attractive glycomimetics as they find significant applications as drug candidates. Examples of iminocyclitol based marketed drugs include Miglustat and Miglitol. Continued research in this area has led to the discovery that synthetic analogues obtained through replacement of one or more of the hydroxyl groups of naturally occurring iminocyclitols with amino functionalities, termed as amino-iminocyclitols, display profound effects on their biological activities, in terms of both selectivity and specificity. Such molecules are expected to be potential lead against viral infections, osteoarthritis, tuberculosis, diabetes, bacterial infections, lysosomal storage disorders etc. due to which chemistry and biology of amino-iminocyclitols have emerged as a fertile area for research. This review covers all the available synthesis of various amino-iminocyclitols and their biological activities. The structure–activity relationship of these molecules with various glycosidases would provide opportunities for the design and development of novel molecules with improved inhibition properties and spur further research towards carbohydrate based drug discovery.

Molecular basis for the affinity and specificity in the binding of five-membered iminocyclitols with glycosidases: an experimental and theoretical synergy

An unusual substituent dictated complementarity in the inhibition of amino-modified five-membered iminocyclitols toward various glycosidases was reported by us. These intriguing results encouraged us to seek a molecular level explanation for the observation that may facilitate the design of specific iminocyclitol inhibitors against glycosidases of choice. We present here a detailed theoretical account that is substantiated with some new experimental investigations on the molecular origins of the differential affinities of iminocyclitols with various glycosidases. The studies involve docking/scoring, molecular dynamics simulations followed by syntheses of a few novel five-membered iminocyclitols and their in vitro binding assays. Directional hydrogen bonds and snug fit of the ligands are implicated as contributory to the observed selectivities. The observed synergy between the computations and experiment is likely to spur further research in the design of novel iminocyclitols with specific inhibitory activities.

Photochemical ring opening of tricyclic hemiketals: Diastereoselective construction of functionalized medium-sized carbocycles and a diquinane

A facile stereoselective construction of functionalized medium-sized carbocycles and a diquinane from bicyclo[3.n.1]alkanones is reported. The key step is the hypervalent iodine mediated photochemical ring opening of tricyclic hemiketals, formed by dihydroxylation of methylene-bicyclo[3.3.1]nonan-9-one and methylene-bicyclo[3.2.1]octan-8-one, to afford eight- and seven-membered carbocyclic rings, respectively. Subsequent transformation of the cyclooctane into a diquinane was achieved using LDA. The reaction was also extended to the synthesis of a fused bicylic system.