Preparation of highly enantiopure β-amino esters by Candida antarctica lipase A

The enantioselectivities for the reactions of aliphatic β-substituted β-amino esters [RCH(NH₂)CH₂CO₂Et with R=Me, Et, n-Pr, i-Pr, CHEt₂, cyclohexyl and Ph] with butyl butanoate in neat butyl butanoate and with 2,2,2-trifluoroethyl butanoate in diisopropyl ether were studied in the presence of Candida antarctica lipase A. Enantioselectivities ranging from good (E=70–100) to excellent (E>100) were commonly observed, allowing gram-scale resolution of the substrates.     

Immobilization of Candida antarctica lipase B on the surface of modified sol–gel matrix

The use of modified sol–gel matrix to immobilize the enzyme Candida antartica lipase B (CALB) was investigated. Free hydroxyl groups on the matrix surface were exploited to covalently immobilize the enzyme. Based from the results, incorporating hydrophobic sol–gel precursor (ethyltrimethoxysilane) enhanced enzyme activity. An enzyme activity of 192.02 U/g beads with 80.88 % attachment was obtained. At alkaline pH, immobilization yield of enzyme increased. The attachment of enzyme on the surface of the matrix was confirmed by scanning electron microscope images. Covalently immobilized CALB on sol–gel supports has higher thermal stability with 2.7 times higher half-life compared to soluble enzymes at 60 °C. This enzyme immobilization system retains the enzyme residual activity even for repetitive use. Hence, the immobilization approach developed recommends its further application.     

Enantioselective acylation of α-aminonitriles catalysed by Candida antarctica lipase. An unexpected turnover-related racemisation

Candida antarctica lipase B (Novozyme 435) catalysed the enantioselective acylation of 2-amino-2-phenylacetonitrile 1 with ethyl phenylacetate affording a near enantiopure product in 47% yield. Acylation of 1 and 2-amino-4-phenylbutyronitrile with ethyl acetate yielded an unexpected partially racemised final product. The racemisation was shown to be turnover related and is ascribed to the increased acidity of the α-proton in the formation of the tetrahedral intermediate in the active site of the enzyme.     

Enzymatic procedure catalysed by lipase from Candida antarctica for the regioprotection–deprotection of glucosamine

Both peracetyl α-glucosamine 3 and its β-epimer 4 undergo alcoholysis with butanol in THF, catalysed by lipase from Candida antarctica (Novozym 435) to afford the triester 6 and diester 9, respectively. Esterification of these compounds, using vinyl acetate in the presence of Novozym 435, gives the partial esters 10 and 11, bearing a deprotected hydroxyl function at C-4, ready for inversion of configuration to open a route in the preparation of galactosamine.     

Selective mono-acylation of 1,2- and 1,3-diols using (α,α-difluoroalkyl)amines

In the reaction of N,N-diethyl-α,α-difluorobenzylamine (DFBA) with 1,2- or 1,3-diols, selective mono-benzoylation occurs to afford mono-esters of the diols in good yield. The reaction is completed under mild conditions in a short reaction time. Further, prim-, sec-, and tert-diols and catechol can be converted to the corresponding mono-benzoates. DFBA is used for the protection of the hydroxy group in sugars. The selective mono-nicotinylation, formylation and pivaloylation of diols are also performed by using the corresponding difluoroalkylamines.     

Candida rugosa Lipase－catalyzed Kinetic Resolution of Hydroxyalkanephosphonates

An efficient lipase-catalyzedenantioselective hydrolysis of butyryloxyalkanephosphonates in water-equillbrated diisopropyl ether was developed. The relationship between the substrates‘ structure and the reactivity, as well as the enantioselectivlty of this enzymatic transformation was studied. The catalytic preference of crude Candida rugosa lipase toward such molecules was assigned according to modified Mosher‘s method and Xray crystallographic analysis. Optically pure 2-hydroxy-2-arylethanephosphonates, 3-hydroxy-3-phenylpropanephosphonate, and 3, 3, 3-trifluoro-2-hydroxypropanephosphonates were conveniently prepared in this manner.     

Resolution of 1-arylalkylamines with 6-(1,2:3,4-di-O-isopropylidene-α-d-galactopyranosyl)hydrogen phthalate

The resolving ability of a new acidic resolving agent, the hydrogen phthalate of 1,2:3,4-di-O-isopropylidene-α-d-galactopyranose 1, against various 1-arylalkylamines 2a–k is described. Treatment of 1 with amines 2a–f to obtain diastereomeric salts 1·(S)2a–f in 2-propanol allowing the corresponding (S)-amines 2a–f to be recovered in good yield and 61–89% ee. Recrystallization in dichloromethane/hexane, and regeneration gave the amines in enhanced enantiomeric purity (>98% ee). 1 resolved 1-phenylpropylamine 2f in high enantiomeric purity (99% ee) than 1-phenylethylamine 2g (11% ee) and o- and m-methoxy 2h–i, o-chloro-2j and p-fluoro-2k substituted 1-arylamines (11–19% ee). A possible chiral recognition mechanism based on the ability of 1 to exist in two conformations is described.     

One-pot synthesis of imidazo[1,2-α]pyridine thioethers using imidazo[1,2-α]pyridines,arylsulfonyl chlorides and hydrazine

Abstract

A one-pot reaction of making RS-substituted imidazo[1,2-α]pyridine derivatives by directly using aryl or alkylsulfonyl chloride and hydrazine was developed, selectively giving good yields of the expected products. Compared with previously reported methods of using ArSO₂NHNH₂ as a sulfur source, this method is much cheaper, more practical and convenient and enriches current methods to make thioether-containing compounds, providing a good example of green chemistry.     

A Synthesis of novel IH-Imidazo[1,2-α]Indole-3-Carboxylates

A route to the uncommon imidazo[1,2-α]indole nucleus 1 is described via functionalisation and annelation of readily accessible 2-amino-indole-3-carboxylates 5. Intramolecular cyclization of a key 2-indolylformamidate 6 was utilised for the preparation of the 3,9-diester intermediates 7.     

Synthesis of the 1,2-Dihydro 1,2-Δ3−azaphosphorines

Abstract

1,2-Dihydro 1,2-Δ³? azaphosphorines were prepared by reaction of dichlorophenylphosphine with two equivalents of imines. 2-Oxo 1,2-azaphospholenes were also obtained in some cases.     

Structural Studies of 3-(1,2-O-Isopropylidene-α-D-xylosyl)-5-phenyl-1,2,4-oxadiazole

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Enzyme-catalyzed direct three-component aza-Diels–Alder reaction using lipase from Candida sp.99–125

The direct three-component aza-Diels–Alder reaction was conducted with lipase as a catalyst for the first time. Under the optimized conditions, the aza-Diels–Alder reaction catalyzed by lipase from Candida sp.99–125 provided the products in moderate to excellent yields. Meanwhile, the endo/exo ratio reached up to 88:12.     

Synthesis of imidazol[1,2-α]pyridine thioethers via using sulfur powder and halides as reactants

Structure containing the CS bond exist widely in nature, drugs and chemical materials. Here, a novel sulfenylation protocol employing an aryl or alkyl halide and odorless and cheap S as reagents was developed, generating regioselective alkyl-S- and Ar-S-substituted imidazol[1,2-α]pyridine derivatives in good yields under relatively environmentally friendly and mild conditions. This protocol enriches current thioether-producing methods, making up for the shortcomings of previous sulfenylation methods which can only make MeS- and ArS-substituted imidazol[1,2-α]pyridine derivatives.     

Synthesis of an analog of ( )-goniopypyrone from 3- O- benzyl-1,2- O-isopropylidene-5- C-phenyl-α-D-gluco-pentofuranose

8,9-Dimethoxy-7-epi-goniopypyrone, an analog of ( )-go-niopypyrone, was synthesized from 3-O-benzyl-1, 2-O-iso-propylidene-5-C-phenyl-α-D-gluco-pentofuranose (3).     

Synthesis of some sulfur-containing pyrido[1,2-α]pyrimidines

4-Methylthiopyrido[1,2-α]pyrimidin-2-one and 2-hydroxypyrido[1,2-α]pyrimidine-4-thione derivatives were synthesized by the addition ofN-(4-R-pyrid-2-yl)acetoacetamides (R = H, Me) to CS₂ under phase-transfer conditions followed by the alkylation of the reaction products with Mel. The molecular structure of 3-acetyl-4-methylthiopyrido[1,2-α]pyrimidin-2-one is established by X-ray analysis.     

Epoxide Hydrolase-catalyzed Resolution of Ethyl 3-Phenylglycidate

Epoxide hydrolase-catalyzed resolution of ethyl 3-phenylglydidate was investigated using resting cells ofPseudomonas sp. BZS21. Under the present conditions 26.2 % of (2R, 3S)-ethyl 3-phenylglycidate with ee value of 94.6 % was obtained from the racemic mixture.     

Conformational analysis of β-1,2-linked mannobiose to mannoheptaose, specific antigen of pathogenic yeast Candida albicans

Candida albicans contains characteristic β-1,2-linked oligomannosyl moieties in the cell wall mannan. Reduction of the reducing termini of these oligosaccharides by NaBH(4) causes a significant downfield shift in the NMR signals for the second and third mannose units and upfield shift of the fourth mannose unit. To show the correlation between the shift in the NMR signals and the conformations of the β-1,2-linked mannooligosaccharides, we performed molecular mechanics calculations. Six energy minima of the β-1,2-linked mannobiose were found in the relaxed map computed using the AMBER force field. Five of the six energy minima could also be generated by a simulated annealing from a 900 K molecular dynamics. Similarly, the solution conformation of the β-1,2-linked mannotriose to mannoheptaose was identified by the high temperature-simulated annealing. In the mannotetraose, the nonreducing terminal mannose unit was located near the reducing terminal one and formed a folded conformation. This result suggests that a mannose unit affects the H-1 chemical shifts of not only the second mannose unit, but also the third and fourth mannose units.     

Evaluation of lipase from Candida rugosa in the resolution of endo-(±)-1,8,9,10,11,11-hexachloropentacyclo[6.2.1.13,6.02,7.05,9]dodecan-4-alcohol

endo-(±)-1,8,9,10,11,11-Hexachloropentacyclo[6.2.1.1^3,6.0^2,7.0^5,9]dodecan-4-ol (±)-7 and exo-(±)-1,8,9,10,11,11-hexachloropentacyclo[6.2.1.1^3,6.0^2,7.0^5,9]dodecan-4-ol (±)-4 have been prepared and the enantiomeric enrichment capacity of the lipase from Candida rugosa in the transesterification with vinyl acetate of these compounds was evaluated. It was verified that the lipase recognize only the alcohol (±)-7, producing endo-(+)-1,8,9,10,11,11-hexachloropentacyclo[6.2.1.1^3,6.0^2,7.0^5,9]dodecan-4-yl acetate (+)-8 with ee >95% and conversion of 44% as the only product.     

Resolution of (±)-2-substituted norbornadiene and hexachloronorbornadiene derivatives using CCL and PLE

(±)-2-Hydroxymethylbicyclo[2.2.1]hepta-2,5-diene, (±)-2-acetoxymethylbicyclo[2.2.1]hepta-2,5-diene and their hexachlorinated derivatives were resolved via CCL- and PLE-catalysed hydrolysis to afford enantiomerically enriched products with e.e.s of 61–93%. The absolute configurations were determined by transforming 2-hydroxymethylbicyclo[2.2.1]hepta-2,5-diene into the 2-formylbicyclo[2.2.1]hepta-2,5-diene with known absolute configuration.     

Thermal and Structural Investigation of the Reaction Between 1,2-propanediol and Co(NO3)2⋅6H2O

The results of an investigation concerning there action between 1,2-propanediol and Co(NO₃)₂⋅ 6H₂O, leading to a complex containing the lactate anion (L) as ligand are presented. The obtained solid homopolynuclear coordination compound[Co₂(OH)₂L₂(H₂O)₂⋅0.5H₂O]_n, has been investigated by thermal analysis, electronic and IR spectroscopy and magnetic methods. Cobalt oxide obtained by thermal decomposition of this coordinative compound was characterized by IR and X-ray spectroscopy. This revised version was published online in July 2006 with corrections to the Cover Date.