Preparation of optically active (2RS,3SR)-2-amino-3-hydroxy-3-phenylpropanoic acid (threo-beta-phenylserine) via optical resolutions by replacing and preferential crystallization

To obtain optically active threo-2-amino-3-hydroxy-3-phenylpropanoic acid (1) via optical resolutions by replacing and preferential crystallization, the racemic structure of (2RS,3SR)-1 hydrochloride [(2RS,3SR)-1.HCl] was examined based on the melting point, solubility, and infrared spectrum. (2RS,3SR)-1.HCl was indicated to exist as a conglomerate at room temperature, although it forms a racemic compound at the melting point. When, in optical resolution by replacing crystallization, L-phenylalanine methyl ester hydrochloride (L-2) was used as the optically active co-solute, (2R,3S)-1.HCl was preferentially crystallized from the supersaturated racemic solution; the use of D-2 as the co-solute afforded (2S,3R)-1.HCl with an optical purity of 95%. In addition, optical resolution by preferential crystallization was successfully achieved to give successively (2R,3S)- and (2S,3R)-1.HCl with optical purities of 90-92%. The (2R,3S)- and (2S,3R)-1.HCl purified by recrystallization from 1-propanol were treated with triethylamine in methanol to give optically pure (2R,3S)- and (2S,3R)-1.     

Optical resolution by preferential crystallization of (1RS,3RS)-1,2,3,4-tetrahydro-6,7-dihydroxy-1-methyl-3-isoquinolinecarboxylic acid

The racemic structure of (1RS,3RS)-1,2,3,4-tetrahydro-6,7-dihydroxy-1-methyl-3-isoquinolinecarboxylic acid [(1RS,3RS)-1] was examined based on the melting point, solubility, and IR spectrum, with the aim of optical resolution by preferential crystallization. (1RS,3RS)-1 was indicated from these results to exist as a conglomerate. The successive optical resolution by preferential crystallization of (1RS,3RS)-1 yielded (1S,3S)- and (1R,3R)-1 with optical purities of 85--95% at 66--81% degrees of resolution, which were fully purified by recrystallization.     

Preparation of optically active threo-2-amino-3-hydroxy-3-phenylpropanoic acid (threo-beta-phenylserine) via optical resolution

To obtain optically active threo-2-amino-3-hydroxy-3-phenylpropanoic acid (1), (2RS,3SR)-2-benzoylamino-3-hydroxy-3-phenylpropanoic acid [(2RS,3SR)-2] was first optically resolved using (1S,2S)- and (1R,2R)-2-amino-1-(4-nitrophenyl)-1,3-propanediol as the resolving agents to afford (2R,3S)- and (2S,3R)-2 in yields of 73% and 66%, based on half of the starting amount of (2RS,3SR)-2. Next, the racemic structures of ammonium and some organic ammonium salts of (2RS,3SR)-2 were examined based on melting point, solubility, and infrared spectrum, with the aim of optical resolution by preferential crystallization. The benzylammonium salt of (2RS,3SR)-2 was suggested to exist as a conglomerate at room temperature, although it forms a racemic compound at the melting point. The optical resolution by preferential crystallization of the racemic salt afforded the (2R,3S)- and (2S,3R)-salts with optical purities of 90-97%. The (2R,3S)- and (2S,3R)-2 obtained from the purified salts were hydrolyzed by reflux in hydrochloric acid to give (2R,3S)- and (2S,3R)-1.     

Synthesis of 2-amino-3-benzyl-5-(p-hydroxyphenyl)pyrazine

2-Amino-3-benzyl-5-(p-hydroxyphenyl)pyrazine (2), a precursor of Watasenia preluciferin (coelenterazine) (1), is widely distributed in marine bioluminescent animals. It was prepared from p-hydroxyphenylglyoxal aldoxime (5) in two steps; by condensation with or-aminophenylpropiononitrile in the presence of TiCl4 in pyridine, followed by reduction of the resulting N-oxide (6) with Zn-AcOH in CH2Cl2 and produced 2, with an 89% overall yield. This procedure was linked with the facile one-step preluciferin synthesis reported in the previous paper. Thus, Watasenia preluciferin (1), frequently required for various chemiluminescent and bioluminescent studies, was coveniently synthesized in three steps from 5, with a 56% overall yield, overcoming the difficulty of obtaining it from natural sources.     

Resolution of (RS)-2-phenylpropanoic acid by enantioselective esterification with dry microbial cells in organic solvent

The microbial direct esterification of racemic 2-phenyl-1-propanoic acid with ethanol by lyophilized mycelium of Aspergillus oryzae MIM and Rhizopus oryzae CBS 112.07 in organic solvents has been investigated. Dry cells of Rhizopus oryzae CBS 112.07 gave the (R)-ethyl ester with high enantiomeric excess (>97%) when the biotransformation was carried out in heptane or pentadecane. Dry mycelium of Aspergillus oryzae MIM furnished the ethyl ester of (S)-(+)-2-phenylpropanoic acid with 90% enantiomeric excess when used in toluene in a temperature range of 20–40°C.     

A chemo-enzymatic approach to optically active 3-(4-methoxycarbonyl)phenyl-2-methyl-1-propanols

With a view to obtaining both enantiomers of 3-(4-methoxycarbonyl)phenyl-2-methyl-1-propanols, (R)-1 and (S)-1, from the respective racemate, (±)-1, the hydrolysis of its acetate, (±)-2, in the presence of porcine pancreatic lipase (PPL) has been studied. The optical puriry of (R)-1 and (S)-1 thus obtained was unsatisfactory (ee 22–27%), and could not be increased beyondee 33% by repeated enzymatic hydrolysis of the unconverted fraction of the acetate. In contrast with this, the biohydrogenation of 3-(4-methoxycarbonyl)phenyl-2-methyl-2-propen-1-ol (4) with fermentingSaccharomyces cerevisiae afforded (S)-1 of considerably higher optical purity (ee 41–90 %, depending on the strain). The stereochemical correlation of the products obtained in the two biochemical processes under study shows that the PPL-catalyzed hydrolysis of (±)-2 produces preferably (R)-1.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 761–766, April, 1995.The authors express their gratitude to the Russian Foundation for Basic Research for financial support (Grant No. 93-03-5893).     

Dirhodium(II)-catalyzed C-H amination reaction of (S)-3-(tert-butyldimethylsilyloxy)-2-methylpropyl carbamate: a facile preparation of optically active monoprotected 2-amino-2-methyl-1,3-propanediol

Dirhodium(II)-catalyzed C-H amination reaction of (S)-3-(tert-butyldimethylsilyloxy)-2-methylpropyl carbamate, which was easily prepared from methyl (S)-2-methyl-3-hydroxypropanoate, proceeded more smoothly than those of their 2-(methoxycarbonyl)propyl derivative to give the corresponding oxazolidinone in excellent yield. The resulting oxazolidinone was converted efficiently into both (R)-monoprotected and (S)-monoprotected 2-amino-2-methyl-1,3-propanediols.     

A facile large scale synthesis of optically active 3-amino-5-(2-pyridyl)-1,4-benzodiazepin-2-one derivatives

A facile method for the synthesis of 3-amino-5-(2-pyridyl)-1,4-benzodiazepin-2-ones (8) mediated by benzotriazole is described. The synthesis and optical resolution of the product by fractional crystallisation proceeds in high yield, under mild conditions and without recourse to toxic reagents or chromatographic separations and hence is amenable to the large scale preparation of these important precursors to potent CCK receptor ligands.     

(RS)-, (R)- and (S)-3-benzyl-3-ethyl 2-oxetanone polymerization with chiral and achiral initiators

The polymerization of 3-benzyl-3-ethyl 2-oxetanones leads to three types of polymers: polyRS (enantiomer excess,ee=0), polyR or polyS (Ree >See) and polyracemate. All these polymers are crystalline and the thermal properties (T _g, meltingT _M and H _M) depend mainly on theee of the polymer. The propagation of the polymerization is not stereospecific. The use of heating-cooling cycles leads to a pure crystalline form melting at the highest temperature. The polyracemate has the behaviour of a pure polymer which melts at a lower temperature, a prolonged heating in the melt induces a strong racemization.

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Zusammenfassung Die Polymerisation von 3-benzyl-3-ethyl 2-oxetanon führt zu drei Polymer Typen: PolyRS (überschuss des Enantiomers,EE=0), PolyR oder PolyS (REE > SEE) und Polyracemate. Alle Polymere sind kristallin und die thermischen Eigenschaften (T _g, SchmelzeT _M und H _M) hängen wesentlich vonEE des Polymers ab. Die Fortpflanzung der Polymerisation ist nicht stereospeeifisch. Die Verwendung von Aufheitzen Abkühl Zyklen führt zu einer reinen kristallinen Form, die bei der höchsten Temperatur schmilzt. Das Polyracemat verhält sich wie ein reines Polymer, das bei niedrigeren Temperatur schmilzt; es racemisiert im Laufe einer verlängerten Erhitzung im Schemlzfluss.

     

Synthesis of α-amino-β-(1-methyl-2-benzimidazolyl)propionic acid

Depending on the reaction conditions, reaction of 1-methyl-2-formylbenzimidazole with hydantoin gives an aldol or crotonoid condensation product. Alkaline hydrolysis of these products gives 1, 2-dimethylbenzimidazole. The dihydro derivative of the crotonoid condensation product can be hydrolyzed to -amino--(1-methyl-2-benzimidazolyl)-propionic acid.     

Transformation of 4-(1-dimethylaminoethylidene)-2-phenyl-5(4H)-oxazolone into methyl 2-benzoylamino-3-oxobutanoate. The synthesis of 1-substituted 4-benzoylamino-3-methyl-5(2H)-pyrazolones

Methyl 2-benzoylamino-3-oxobutanoate ( 3 ) was prepared from hippuric acid (1) which was converted with N,N-dimethylacetamide and phosphorus oxychloride into 4-(1-dimethylaminoethylidene)-2-phenyl-5(4H)-oxazolone ( 2 ) followed by hydrolysis with hydrochloric acid in methanol. Compound 3 was treated with hydrazines 4 to give 4-benzoylamino-3-methyl-1H-pyrazol-5(2H)-one ( 6a ) and its 1-substituted derivatives 6b-j . The corresponding hydrazones 5f, i, j were isolated as intermediates.     

A facile, microwave-assisted synthesis of novel optically active polyamides derived from 5-(3-methyl-2-phthalimidylpentanoylamino)isophthalic acid and different diisocyanates

5-(3-Methyl-2-phthalimidylpentanoylamino)isophthalic acid as a novel aromatic diacid monomer was prepared in three steps. In the first step, phthalic anhydride was reacted with l-isoleucine in acetic acid solution, and the resulting imide acid was obtained in high yield. In the second step, treatment of this imide acid with excess thionyl chloride gave aliphatic acid chloride in good yield. In the last step, this acid chloride was reacted with 5-aminoisophthalic acid to provide novel bulky chiral aromatic diacid monomer. The direct polycondensation reactions of this diacid with several aromatic and aliphatic diisocyanates such as 4,4′-methylenebis(phenyl isocyanate), toluylene-2,4-diisocyanate, isophorone diisocyanate and hexamethylene diisocyanate were carried out under microwave irradiation. In order to compare this method with classical heating, the polymerization reactions were also performed under solution polycondensation conditions. The polymerization reactions occurred rapidly under microwave conditions and produced a series of novel optically active polyamides (PA)s containing pendent phthalimide group, with good yields and moderate inherent viscosities of 0.17-0.60 dL/g. Some of the new PAs showed good solubility and are readily soluble in organic solvents. The resulting macromolecules were characterized by FT-IR, specific rotation, and representative ones by ¹H NMR, elemental and thermogravimetric analyses (TGA).     

Enantioselective oxidation of (RS)-2-phenyl-1-propanol to (S)-2-phenylpropanoic acid with Gluconobacter oxydans: simplex optimization of the biotransformation

The microbial oxidation of racemic 2-phenyl-1-propanol by Gluconobacter oxydans DSM 50049 was investigated. Whole bacterial cells were used to produce (S)-(+)-2-phenylpropanoic acid with high enantiomeric excess (E>200). A simplex sequential method was employed as an experimental design to guide the optimization process. Temperature of 26–28°C, pH 6.0–6.2, substrate concentration of 20–25 mM and agitation of 150 rpm have been found the best conditions to achieve the highest reaction rates and enantioselectivities.     

Preparative resolution of (±)-trans-1,2-diaminocyclohexane by means of preferential crystallization of its citrate monohydrate

Even if (±)-trans-1,2-diaminocyclohexane crystallizes as a conglomerate, its low melting point (?10 °C) and its sensitivity to light, CO₂, O₂, and moisture make this molecule difficult to resolve. It has been shown that the citrate monohydrate of this compound crystallizes as a stable conglomerate with a high thermal stability (up to 163 °C) with no drawbacks as to those listed above for the pure diamine. The crystal structure of this salt, resolved by single crystal X-ray diffraction, reveals structural features consistent with the thermal stability of this phase. Several preferential crystallization attempts (AS3PC) have been performed at a 100 ml scale and at a one liter scale in water with and without additives. Finally a productivity of 40 g per batch per liter of solvent per hour was achieved with a crude enantiomeric purity better than 90%. A simple recrystallization of the crude crops gives quantitatively the crystalline compound with an ee >99% proving the absence of partial solid solution at room temperature.