105227-22-3Relevant academic research and scientific papers
Probing the enantioselectivity of a diverse group of purified cobalt-centred nitrile hydratases
Van Pelt,Zhang,Otten,Holt,Sorokin,Van Rantwijk,Black,Perry,Sheldon
experimental part, p. 3011 - 3019 (2011/06/17)
In this study a diverse range of purified cobalt containing nitrile hydratases (NHases, EC 4.2.1.84) from Rhodopseudomonas palustris HaA2 (HaA2), Rhodopseudomonas palustris CGA009 (009), Sinorhizobium meliloti 1021 (1021), and Nitriliruptor alkaliphilus (iso2), were screened for the first time for their enantioselectivity towards a broad range of chiral nitriles. Enantiomeric ratios of >100 were found for the NHases from HaA2 and CGA009 on 2-phenylpropionitrile. In contrast, the Fe-containing NHase from the well-characterized Rhodococcus erythropolis AJ270 (AJ270) was practically aselective with a range of different α-phenylacetonitriles. In general, at least one bulky group in close proximity to the α-position of the chiral nitriles seemed to be necessary for enantioselectivity with all NHases tested. Nitrile groups attached to a quaternary carbon atom were only reluctantly accepted and showed no selectivity. Enantiomeric ratios of 80 and >100 for AJ270 and iso2, respectively, were found for the pharmaceutical intermediate naproxennitrile, and 3-(1-cyanoethyl)benzoic acid was hydrated to the corresponding amide by iso2 with an enantiomeric ratio of >100.
Synthesis of 4-quinolones via cyclocondensation of substituted ortho-amidoacetophenones: A refit to the camps cyclization by applying trimethylsilyl trifluoromethanesulfonate/triethylamine
Eidamshaus, Christian,Triemer, Therese,Reissig, Hans-Ulrich
supporting information; experimental part, p. 3261 - 3266 (2011/11/30)
A modification of the classical Camps cyclization is described. A series of substituted 4-quinolone derivatives is prepared via trimethylsilyl trifluoromethanesulfonate/triethylamine induced cyclocondensation of substituted ortho-amidoacetophenones. The process shows a broad substrate scope and allows selective preparation of 2-aryl- and 2-alkyl-substituted 4-quino-lones. Enantiopure starting materials react without loss of optical purity using the modified conditions. Subsequent transformations of the products involving preparation of a 4-quinolyl nonaflate and O-selective methylation are also described. Georg Thieme Verlag Stuttgart · New York.
Synthesis of chiral disulfides: Potential reagents for enantioselective sulfurization
Mukhlall, Joshua A.,Noll, Bruce C.,Hersh, William H.
scheme or table, p. 199 - 212 (2012/01/06)
Synthesis of chiral phosphorothioates for use as antisense oligonucleotides might benefit from the use of chiral disulfides. This paper reports the synthesis of chiral analogs of phenylacetyl disulfide and of 5-methyl-3H-1,2,4-dithiazol-3-one from the same set of 2-arylalkanoic acids. The X-ray crystal structures of the disulfides derived from (R) and [S]-2-phenylpropanoic acid establish the stereochemistry and the helicity of these materials, and density functional theory calculations suggest that the high specific rotations can be due to preferred retention of this helicity in solution. Chiral HPLC showed that the final products were formed with enantiomeric purities from 86.1% to >99.9%.
Synthesis, stereoselective enzymatic hydrolysis, and skin permeation of diastereomeric propranolol ester prodrugs
Udata, Chandrasekhar,Tirucherai, Giridhar,Mitra, Ashim K.
, p. 544 - 550 (2007/10/03)
Four diastereomeric propranolol ester prodrugs (1S2S, 1S2R, IR2S, 1R2R) were synthesized by treating pure R- and S-propranolol hydrochloride with pure enantiomers R- and S-phenylbutyryl chloride. A HPLC technique using α- 1 acid glycoprotein (chiral AGP) column was developed to study the racemization of propranolol enantiomers during synthesis and hydrolysis studies. A reversed phase HPLC method was also developed to simultaneously analyze propranolol and the ester prodrug. Hydrolysis of these esters was studied in different rat tissue homogenates, i.e., liver, intestine, plasma, skin, brain, and pure plasma cholinesterases, i.e., butyryl cholinesterase (EC 3.1.1.8) and acetyl cholinesterase (EC 3.1.1.7). In vitro percutaneous permeation studies across full thickness shaved rat skin were performed using standard side-by-side diffusion cells at 37 °C. The disappearance of the diastereomeric ester prodrugs in rat tissue homogenates followed apparent first-order kinetics and was stereoselective. The ratio of brain to plasma hydrolytic rate constants are 27.8, 5.58, 6.07, and 2.97 for 1S2S, 1R2R, 1R2S, and 1S2R esters, respectively. Hydrolysis of all four diastereomeric ester prodrugs was faster by acetyl cholinesterase than butyryl cholinesterase and is stereoselective. The permeability coefficients [K(p) x 103 (cm h-1)] are 1.40 ± 0.30, 1.41 ± 0.27, 42.20 ± 1.24, 29.26 ± 3.41, 16.27 ± 3.12, 12.99 ± 2.84 for (R)-propranolol, (S)-propranolol, 1S2S, 1R2S, 1S2R, and 1R2R ester prodrugs, respectively. The results indicate that the 1R2S diastereomeric ester prodrug of propranolol shows greatest stability in liver and intestinal tissues while it exhibits fairly rapid conversion in plasma. The results also suggest the configuration on the second chiral carbon atom to be the determinant in the rate of hydrolysis of all the diastereomeric prodrugs in all biological media examined. The K(p) of all four prodrugs markedly increased compared to that of the parent drug, with 1S2S showing a 30-fold increase in skin permeability, the highest among all four prodrugs.
Enantiospecific synthesis of 4-(4'-methoxyphenyl)-hexan-3-one as precursor for optically active (pS) or (pR) isomer of (Z) or (E)-3-(2'-((N,N-dimethylamino)methylferrocenyl)-4-(4''-methoxyphenyl)-hex-3-ene
Malezieux, Bernard,Gruselle, Michel,Troitskaya, Ludmila,Sokolov, Viatcheslav
, p. 259 - 269 (2007/10/03)
We describe herein an original method for the preparation of enantiomerically pure (Z)- or (E)-3-(2'-((N,N-dimethylamino)methylferrocenyl)-4-(4''-methoxyphenyl)-hex-3-ene possessing a p(S) or p(R) plane of chirality. The key step of the synthesis lies in obtaining enantiomerically pure (R) or (S) 4-(4'-methoxyphenyl)-hexan-3-one whose reaction with the lithiated N,N-dimethylaminomethylferrocene leads to two enantiomerically pure amino-alcohol diastereomers (pS,3S,4R) and (pR,3S,4R), or (pS,3R,4S) and (pR,3R,4S) respectively. Subsequent dehydration yields a mixture of three olefins, namely, two trisubstituted olefins and either the (Z)- or (E)-tetrasubstituted olefin with respect to the starting amino-alcohol diastereomer. Additionally we obtained the enantiomerically pure (R)- and (S)-4-phenyl-hexan-3-one and the corresponding diastereomeric amino-alcohols.
