Racemic Acetate Research Articles

Practical Chemo-Enzymatic Process for the Preparation of (1R,cis)-2-(2,2-Dihaloethenyl)-3,3-dimethylcyclopropane Carboxylic Acids

A practical chemo-enzymatic process for the preparation of optically active (1R,cis)-2-(2,2-dichloro (or dibromo)ethenyl)-3,3-dimethylcyclopropane carboxylic acids (permethrinic or deltamethrinic acids) from racemic 1,1,1-trichloro-2-acetoxy-4-methyl-3-pentene is described. The key intermediate, enantiopure (R)-1,1,1-trichloro-2-hydroxy-4-methyl-3-pentene, is prepared by a lipase catalysed kinetic resolution of the racemic acetate. The reaction mixture, containing (R)-alcohol and the unreacted (S)-acetate, is directly acetylated by a haloacetyl halide, and the products are separated by distillation. The (S)-acetate is racemized, and the (R)-haloacetate is transformed to the corresponding glycinate hydrochloride, followed by diazotization to (R)-1,1,1-trichloro-4-methyl-3-penten-2-yl diazoacetate. The stereoselective carbenic dediazotization of the (R)-diazoacetate furnishes the optically active (1R,4R,5S)-6,6-dimethyl-4-trichloromethyl-3-oxobicyclo[3.2.0]hexan-2-one, which is transformed to the desired en...

A concise synthesis of homochiral sedamines and related alkaloids. A new reductive application of Jacobsen's catalyst

Two methods for the generation of both enantiomers of sedamine [1-methyl-2-(2-phenyl-2-hydroxy-1-ethyl)piperidine] in high optical purity have been elaborated. The first utilises the lipase-mediated kinetic resolution of racemic acetates and the second involves the NaBH 4 mediated reduction of ketones catalysed by Jacobsen's catalyst. Some related applications of these reactions are also disclosed.

Anticonvulsant and sodium channel-blocking properties of novel 10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide derivatives.

A series of esters of the major metabolite of oxcarbazepine (2), 10, 11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide, were synthesized and evaluated for their anticonvulsant and brain sodium channel-blocking properties. The compounds were assayed intraperitoneally and per os in rats against seizures induced by maximal electroshock (MES). Neurologic deficit was evaluated by the rotarod test. The enantiomeric acetates (R)-11 and (S)-12 were the most active of the series against MES-induced seizures with oral ED(50) values at t(max) of 10.9 +/- 2.3 and 4.7 +/- 0.9 mg/kg, respectively. After intraperitoneal administration, carbamazepine (1) behaved more potently than 2 and all other new dibenz[b, f]azepine-5-carboxamide derivatives in the MES test; compounds 2 and 12 were equally potent. In the rotarod test, low doses of 1 produced considerable motor impairment, which did not occur with 2, enantiomeric alcohols (S)-6, (R)-7, and racemic alcohol 8, or racemic acetate 10 or (R)-11. The potencies of the racemic and enantiomerically pure alcohols 8, (S)-6, and (R)-7 derived from 2 in the MES and rotarod test were found to be similar between them, and consequently they exhibit similar protective index values. All three forms of the alcohol and their corresponding acetates (pairs 8 & 10, 6 & 12, and 7 & 11) were found to differ in the MES or rotarod tests; the ED(50) value for (S)-6 against MES-induced seizures was nearly 3-fold that for (S)-12. The protective index also differed markedly between all stereoisomers of the alcohol and their corresponding acetates, most pronouncedly for compound (S)-12 which attained the highest value (12.5) among all compounds tested. Blockade of voltage-sensitive sodium channels was studied by investigating [(3)H]batrachotoxinin A 20-alpha-benzoate ([(3)H]BTX) binding. Acetates (R)-11 and (S)-12 were more potent than the standards 1 and 2 at inhibiting the binding of [(3)H]BTX to sodium channels and the influx of (22)Na(+) into rat brain synaptosomes. It is concluded that acetates (R)-11 and (S)-12 are not simple metabolic precursors of alcohols (R)-7 and (S)-6 in rodents but that they possess anticonvulsant and sodium channel-blocking properties in their own right.

Enantioselective synthesis of ( S)- and ( R)-mappicines and their analogues

The naturally occurring alkaloids, camptothecin and mappicine ketone were converted to racemic mappicine acetate which was enantioselectively hydrolyzed to ( S)- and ( R)-mappicines in high optical purity using baker's yeast and a lipase, Amano PS. Treatment of the racemic acetate with baker's yeast afforded ( S)-mappicine while with Amano PS yielded (R)-mappicine. 9-Methoxycamptothecin and 9-methoxymappicine ketone underwent similar conversion to ( S)- and ( R)-9-methxymappicines.

A novel building block for the synthesis of isofagomin analogues

The de novo synthesis of the novel potent building blocks phenyl ( R)-3-acetoxymethyl-3,6-dihydro-2 H-pyridine-1-carboxylate (−)- 7 and phenyl ( S)-3-butyryl-oxymethyl-3,6-dihydro-2 H-pyridine-1-carboxylate (+)- 8 starting from commercially available methyl-1-benzyl-4-oxo-3-piperidinecarboxylate is described. The key steps are the enantioselective esterification of the racemic alcohol 6 and the enantioselective hydrolysis of the racemic acetate 5, respectively, using lipase P from Pseudomonas caepacia.

Biotransformations of racemic acetates by potato and topinambur tubers

The hydrolysis of acetates: (±)-1-phenylethyl ((±)- 1), (±)-1-(1-naphthyl)ethyl ((±)- 2), (±)-1-(2-naphthyl)ethyl ((±)- 3) and (±)-menthyl ((±)- 4) with the use of potato and topinambur (artichoke) tubers results in the production of alcohols, which in the same environment are oxygenated to ketones. Pure S-1-phenylethyl acetate has been produced.

Chiral synthesis of alpha-phenylpyridylmethanols with Rhizopus arrhizus

The bioreduction of 2-benzoylpyridine (1a) with Rhizopus arrhizus afforded (S)-(+)-alpha-phenyl-2-pyridylmethanol (2a) in 82% enantiomeric excess (e.e.) while the asymmetric hydrolysis of its racemic acetate resulted in the antipode (R)-(-)-2a with 24% optical purity.

Synthesis of (.+-.)-Pseudodistomins A and B Acetates.

Pseudodistomins A and B, piperidine alkaloids isolated from the Okinawan tunicate Pseudodistoma kanoko, have been synthesized as their racemic acetates via a route involving Grignard coupling reaction to provide unambiguous proof of their structures.

Synthesis of the C2-Symmetric, Macrocyclic Alkaloid, (+)-Xestospongin A and Its C(9)-Epimer, (−)-Xestospongin C: Impact of Substrate Rigidity and Reaction Conditions on the Efficiency of the Macrocyclic Dimerization Reaction

Xestospongin A [also known as araguspongine D (1)], a C2-symmetric macrocyclic alkaloid isolated from the sponge Xestospongia exigua (Xestospongia sp.), and its C(9) epimer xestospongin C [also known as araguspongine E (2)] have been synthesized. The route capitalizes on the facile condensation between 5-halovaleraldehydes and 1,3-aminoalcohols to produce an oxaquinolizidine ring system in which all proper relative stereochemical relationships are controlled by equilibration. A linchpin synthesis was used to construct one key monomeric precursora 2,5-disubstituted thiophene derivative 26 [N≡CCH2CH(OH)-2-Th-5-CH2CH2CH(CH(OMe)2)CH2CH2CH2Cl]. A second precursor lacking the thiophene ring 38 [N≡CCH2CH(OH)(CH2)6CH(CH(OMe)2)CH2CH2CH2Cl] was assembled in a similar fashion. The carbinol center in each of these precursors was efficiently resolved enzymatically; lipase (PS-30) hydrolysis of the racemic acetate derivative of the thiophenemethanol derivative 26 and SP-435-catalyzed esterification of the β-hydroxynitr...

The first total synthesis of (−)-mitragynine, an analgesic indole alkaloid in mitragyna speciosa

Starting from an optically pure alcohol, ( R)-( 3), which was prepared by enzymatic hydrolysis of the racemic acetate ( 2) or enantioselective reduction of the ketone derivative ( 4), the chiral total synthesis of mitragynine ( 1), a major corynanthe-type indole alkaloid having an analgesic effect in Mitragyna speciosa, was accomplished.

ChemInform Abstract: Kinetic Resolution of Racemic Acetates by Transesterification Catalyzed by Chiral Alkoxocopper(I) Complexes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Biotransformations with Rhizopus arrhizus: Preparation of the enantiomers of 1-phenylethanol and 1-(fo-, m- and p-methoxyphenyl)ethanols

Abstract The fungus Rhizopus arrhizus has been used for the reduction of acetophenone and its o -, m - and p -methoxy derivatives 1a–d to the corresponding ( S )-(−)-alcohols. Their racemic acetates were also hydrolyzed to ( R )-(+)-alcohols. The analysis of products revealed that maximum enantioselectivity (78–88 %ee) could be obtained using m -methoxy acetophenone as substrate.

Kinetic resolution of racemic acetates by transesterification catalyzed by chiral alkoxocopper(I) complexes

Kinetic resolution of racemic acetates, which has been accomplished mainly by means of Lipases, was examined by use of a variety of catalyst systems involving chiral alkoxocopper(I) complexes. When a t BuOCu/( R)-BINAP (1:1) system was used as a catalyst in ethanol, (±)-1-acetoxy-1-naphthylethane ( 4b) was kinetically resolved to give ( S)-1-acetoxy-1-naphthylethane in 30% ee at 74% conversion.

Enzymatic resolution of 1‐ferrocenylethanol and 1‐ferrocenyl‐2,2,2‐trifluoroethanol using lipases

Abstract1‐Ferrocenylethanol and 1‐ferrocenyl‐2,2,2‐trifluoroethanol were resolved with transesterification by lipases to the optically active (R)‐esters and (S)‐alcohols. Enzymatic hydrolysis of the racemic esters of 1‐ferrocenylethanol using lipases yielded (R)‐alcohol and (S)‐esters. Enantioselective hydrolysis of racemic acetate or butanoate of 1‐ferrocenyl‐2,2,2‐trifluoroethanol yielded the (S)‐alcohol and (R)‐esters. Enzymatic hydrolysis of (±)‐acetate of 1‐ferrocenyl‐2,2,2‐trifluoroethanol yielded (R)‐alcohol and (S)‐acetate, but the equivalent (±)‐butanoate was not hydrolyzed.

Synthesis of enantiomerically enriched anti-homoallyl alcohols mediated by Crude Chicken Liver Esterase (CCLE)

Enantiomerically enriched anti-homoallyl alcohols were synthesized in 67−>99% enantiomeric purities via enantioselective hydrolysis of the corresponding racemic acetates mediated by Crude Chicken Liver Esterase (CCLE).

Biocatalytic synthesis of (S)-2-tridecanyl acetate and (S)-2-pentadecanyl acetate, aggregation pheromone components ofDrosophila mulleri andD. busckii, by enantioselective hydrolysis with lipase

The two chiral pheromone acetates, (S)-2-tridecanyl acetate and (S)-2-pentadecanyl acetate, were synthesized with an enantiomeric excess (e.e.) of almost 100% byPseudomonas cepacia lipase-catalyzed hydrolysis of their corresponding racemic acetates in an acetone-water solvent system.

Biocatalytic Approach to Optically Active Baylis-Hillman Reaction Products

Pig liver acetone powder (PLAP) catalyzes enantioselective hydrolysis of racemic acetates of Baylis-Hillman Reaction products.

Crude Chicken Liver Esterase Mediated Resolution of Homoallyl Alcohols

Racemic acetates of homoallyl alcohols have been enantioselectively hydrolyzed by crude chicken liver esterase (liver acetone powder) to provide homoallyl alcohols in 72-98% optical purities.

Enzymatic enantioselective hydrolysis of acyloxyferrocenophanes using lipases and esterases

AbstractEnantioselective hydrolysis of racemic acetate or butyrates of 1‐hydroxy [3](1,1′) ferrocenophane and endo‐1‐hydroxy [4](1,2) ferrocenophane using lipases, pig liver esterase and horse liver esterase resulted in the formation of (R)‐alcohols and (S)‐esters.

Enantiocomplementary Resolution of 2-Phenylthio-2-cyclopentenol and 2-Phenylthio-2-cyclohexenol Using the Same Lipase

Both racemic 2-phenylthio-2-cyclopentenol (±)-(3a) and 2-phenylthio- 2-cyclohexenol (±)-(3b) afford the corresponding (R)-acetates (R)-4a,b and the unreacted (S)-alcohols (S)-3a,b, respectively, in excellent op- tical and chemical yields on treatment with vinyl acetate in the pre- sence of lipase PS in dichloromethane. On the other hand, both racemic acetates (±)-4a,b obtained from racemic 2-phenylthio-2-cyclopentenol (±)-(3a) and 2-phenylthio-2-cyclohexenol (±)-(3b) afford the corres- ponding (R)-alcohols (R)-3a,b and the unreacted (S)-acetates (S)-4a,b, respectively, in excellent optical and chemical yields on stirring in a phosphate buffer-acetone solution in the presence of the same lipase