- Route exploration and synthesis of the reported pyridone-based PDI inhibitor STK076545
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The enzyme protein disulfide isomerase (PDI) is essential for the correct folding of proteins and the activation of certain cell surface receptors, and is a promising target for the treatment of cancer and thrombotic conditions. A previous high-throughput screen identified the commercial compound STK076545 as a promising PDI inhibitor. To confirm its activity and support further biological studies, a resynthesis was pursued of the reported β-keto-amide with an N-alkylated pyridone at the α-position. Numerous conventional approaches were complicated by undesired fragmentations or rearrangements. However, a successful 5-step synthetic route was achieved using an aldol reaction with an α-pyridone allyl ester as a key step. An X-ray crystal structure of the final compound confirmed that the reported structure of STK076545 was achieved, however its lack of PDI activity and inconsistent spectral data suggest that the commercial structure was misassigned.
- Dockendorff, Chris,Flaumenhaft, Robert,Greve, Eric,Lin, Lin,Lindeman, Sergey V.,Scartelli, Christina
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p. 6665 - 6681
(2020/09/21)
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- A simple and facile method for regio- and stereoselective bromoformyloxylation and bromoacetoxylation of olefins using NH4Br and oxone
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A mild and efficient protocol for the preparation of bromoformates as well as bromoacetates from olefins using NH4Br and oxone in nucleophile sources (DMF or DMA) without employing catalyst at room temperature is described. This method is facile, environmentally friendly and cost effective. A variety of terminal, internal and cyclic alkenes reacted smoothly to give the corresponding bromoformate and acetate products in good to excellent yields. Moreover, 1,2-disubstituted olefins provided moderate to excellent diastereoselectivity.
- Naresh, Mameda,Swamy, Peraka,Arun Kumar, Macharla,Mahender Reddy, Marri,Srujana, Kodumuri,Narender, Nama
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supporting information
p. 3926 - 3933
(2014/07/08)
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- Chemoenzymatic approach to optically active phenylglycidates: Resolution of bromo- and iodohydrins
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Enantiomerically enriched phenylglycidates, precursors of the taxol C-13 phenylisoserine side chain and diltiazem, were prepared by kinetic resolution of anti-2-bromo-3-hydroxy- and anti-3-hydroxy-2-iodophenylpropanoates to provide enantioriched (2R,3R)- and (2S,3S)-halohydrins. The bulkiness and inflexibility of bromo and iodo groups in halohydrins have made them inaccessible to the active site of most of the lipases utilized for the hydrolysis of their acyloxy derivatives. In a set of 22 hydrolases screened herein, including native as well as commercial enzymes, only Aspergillus niger (Lipase AS, AMANO) could catalyze the hydrolysis with high enantioselectivity (E = 176). The resolved halohydrins easily underwent transformation to the corresponding (2S,3R)- and (2R,3S)-phenylglycidates.
- Anand, Naveen,Kapoor, Munish,Koul, Surrinder,Taneja, Subhash C.,Sharma, Rattan L.,Qazi, Ghulam N.
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p. 3131 - 3138
(2007/10/03)
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- Stereoselective chemoenzymatic process for the preparation of optically enriched phenylglycidates as precursors of taxol side chain
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The present invention relates to a novel and efficient chemoenzymatic process of preparation of optically active trans alkyl phenylglycidates. The invention particularly discloses a novel process for the chemoenzymatic synthesis of two enantiomers of tran
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- The asymmetric synthesis of β-aryl-α-hydroxy esters from β-aryl-α,β-dihydroxy esters
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α,β-Dihydroxy-β-aryl esters obtained via Sharpless asymmetric dihydroxylation (AD) of substituted cinnamate esters are reduced by sequential reaction with trimethyl orthoacetate and acetyl bromide followed by catalytic hydrogenolysis in methanol to give enantiomerically enriched β-aryl-α-hydroxy esters.
- Lawrence, Nicholas J,Brown, Stephen
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p. 613 - 619
(2007/10/03)
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- Synthesis of taxoids I. Regioselective Lewis acid-mediated ring-opening of aryl orthoacetates
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The reaction of aryl orthoacetates with acetyl bromide readily proceeded regioselectively to afford the desirable aryl bromides in the presence of tin(II) or zinc bromide as a catalyst. The synthesis of some docetaxel derivatives is also described by using this improved process.
- Harada, Naoyuki,Hashiyama, Tomiki,Ozaki, Kunihiko,Yamaguchi, Tetsuo,Ando, Akira,Tsujihara, Kenji
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p. 305 - 318
(2007/10/03)
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- A Simplified Procedure for the Stereospecific Transformation of 1,2-Diols into Epoxides
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A simple, 'one-pot' procedure for the conversion of vicinal diols into epoxides via halohydrin ester intermediates has been developed.This method tolerates a wide range of functionality including acid sensitive functional groups.The transformation proceed
- Kolb, Hartmuth C.,Sharpless, K. Barry
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p. 10515 - 10530
(2007/10/02)
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- Mechanism of Dehydroacetoxylation of Methyl 3-Acetoxy-3-aryl-2-halogenopropanoates
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The rate of sodium methoxide-induced dehydroacetoxylation of the diesters p-RC6H4CH(OAc)CXHCO2Me (X= Br or Cl) has been studied as a function of the para-substituent.The results correspond to the para-substituent effects expected for proton abstraction from C-2, as estimated from the diastereoisomerisation of model compounds under similar conditions.This suggests that the elimination occurs via a carbanion mechanism, with C(2)-H bond-breaking rate-determining.The apparent insensitivity of the kinetic behaviour to configuration differences, together with the response of the reactions to the effect of the 3-substituent, is interpreted in terms of inductive stabilisation by the 2-halogen atom, which tends to localise the incipient negative charge at C-2, inhibiting distortion of its tetrahedral geometry.
- Cabaleiro, Mercedes C.,Garay, Raul O.
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p. 1091 - 1096
(2007/10/02)
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- SOLVENT SHIFTS INDUCED BY DIMETHYLSULPHOXIDE IN α-PROTON MAGNETIC RESONANCES OF CARBONYL COMPOUNDS
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The chemical shifts of α- and β-proton resonances of a number of carbonyl compounds in carbon tetrachloride and dimethylsulphoxide have been determined.The magnitude of the effect of the solvent change on the α-proton resonances seems to vary directly wit
- Cabaliero, M. C.,Giagante, N. N.
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p. 1829 - 1832
(2007/10/02)
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