New cyclohexyl-based chiral auxiliaries: Enantioselective synthesis of α-hydroxy acids

Basavaiah, Deevi; Krishna, P. R.

doi:10.1016/0040-4020(95)00771-y

Cited by 24 publications

(8 citation statements)

References 14 publications

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“…These latter were both employed for the preparation of the (+)‐menthyl ester derivative 4 . Indeed, acid 2 was condensed with (+)‐menthol in the presence of p ‐toluenesulfonic acid , while ester 3 underwent a modification of the titanium (IV) alkoxyde‐catalyzed transesterification developed by Seebach . Accordingly, treatment of 3 with (+)‐menthol in the presence of a catalytic amount of titanium isopropoxide (20 mol %) in toluene provided the corresponding (+)‐menthyl ester 4 in high yield.…”

Section: Resultsmentioning

confidence: 99%

Site‐directed Mutagenesis of Key Residues Unveiled a Novel Allosteric Site on Human Adenosine Kinase for Pyrrolobenzoxa(thia)zepinone Non‐Nucleoside Inhibitors

et al. 2015

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Most nucleoside kinases, besides the catalytic domain, feature an allosteric domain which modulates their activity. Generally, non-substrate analogs, interacting with allosteric sites, represent a major opportunity for developing more selective and safer therapeutics. We recently developed a series of non-nucleoside non-competitive inhibitors of human adenosine kinase (hAK), based on a pyrrolobenzoxa(thia)zepinone scaffold. Based on computational analysis, we hypothesized the existence of a novel allosteric site on hAK, topographically distinct from the catalytic site. In this study, we have adopted a multidisciplinary approach including molecular modeling, biochemical studies, and site-directed mutagenesis to validate our hypothesis. Based on a three-dimensional model of interaction between hAK and our molecules, we designed, cloned, and expressed specific, single and double point mutants of hAK (Q74A, Q78A, H107A, K341A, F338A, and Q74A-F338A). Kinetic characterization of recombinant enzymes indicated that these mutations did not affect enzyme functioning; conversely, mutated enzymes are endowed of reduced susceptibility to our non-nucleoside inhibitors, while maintaining comparable affinity for nucleoside inhibitors to the wild-type enzyme. This study represents the first characterization and validation of a novel allosteric site in hAK and may pave the way to the development of novel selective and potent non-nucleoside inhibitors of hAK endowed with therapeutic potential.

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Section: Resultsmentioning

confidence: 99%

Site‐directed Mutagenesis of Key Residues Unveiled a Novel Allosteric Site on Human Adenosine Kinase for Pyrrolobenzoxa(thia)zepinone Non‐Nucleoside Inhibitors

et al. 2015

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“…Heating the mixture of amide 6 and KOH in ethylene glycol resulted in formation of tertiary α-hydroxycarboxylic acid 7 . Comparison of the optical rotation of synthesized 7 with the literature indicated an absolute configuration of R.…”

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confidence: 89%

Addition–Rearrangement of Ketenes with Lithium N-tert-Butanesulfinamides: Enantioselective Synthesis of α,α-Disubstituted α-Hydroxycarboxylic Acid Derivatives

Tang

Yao

et al. 2019

Org. Lett.

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Addition of the lithium salts of chiral Nsubstituted tert-butanesulfinamides to ketenes and subsequent silylation initiates stereoselective [2,3]-rearrangement, which affords enantioenriched α,α-disubstituted α-sulfenyloxy carboxamides through a reaction that faithfully transfers the absolute stereochemistry of the lithiated sulfinylamides to the α-carbon of the amide products. This addition−rearrangement can be performed together with ketene formation from acyl chloride in a single flask, providing a new and practical synthetic route to α-hydroxycarboxylic acid derivatives.

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“…55,56 Chiral 2-phenoxycyclohexanols have been used as auxiliaries by forming esters with glyoxylic acid; addition of alkylzinc reagents to the aldehyde then affords a route to α-hydroxy acids. 57 Roush has reported an improved cyclic amide derivative of tartaric acid as an auxiliary for the addition of chiral allylboronates to aldehydes. 58 Allylsilanes undergo addition to ketones mediated by a norpseudoephedrine derivative; 59 this is a development of the same reaction with aldehydes, but surprisingly gives the opposite facial selectivity with ketones.…”

Section: Other Addition Reactionsmentioning

confidence: 99%

Asymmetric processes

Regan¹

1998

J. Chem. Soc., Perkin Trans. 1

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New cyclohexyl-based chiral auxiliaries: Enantioselective synthesis of α-hydroxy acids

Cited by 24 publications

References 14 publications

Site‐directed Mutagenesis of Key Residues Unveiled a Novel Allosteric Site on Human Adenosine Kinase for Pyrrolobenzoxa(thia)zepinone Non‐Nucleoside Inhibitors

Site‐directed Mutagenesis of Key Residues Unveiled a Novel Allosteric Site on Human Adenosine Kinase for Pyrrolobenzoxa(thia)zepinone Non‐Nucleoside Inhibitors

Addition–Rearrangement of Ketenes with Lithium N-tert-Butanesulfinamides: Enantioselective Synthesis of α,α-Disubstituted α-Hydroxycarboxylic Acid Derivatives

Asymmetric processes

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