The expulsion of formic acid and methyl formate during the fragmentation of 3-phenylpropionic acid derivatives under electron-impact

Examination of the mass spectra of several 3-arylpropionic acids and methyl esters showed that one of the major fragmentation processes corresponded to the expulsion of a molecule of formic acid or methyl formate directly from the molecular ion.     

Dynamic kinetic resolution of racemic tropic acid ethyl ester and its derivatives

The dynamic kinetic resolution of racemic mixtures of tropic acid ethyl ester under substrate racemizing conditions was studied using lipase PS with a ruthenium catalyst. Isopropenyl acetate was used as an acyl donor, since it was found to be compatible with both catalysts; this resulted in an efficient dynamic kinetic resolution. With this process, a variety of racemic tropic acid ethyl esters were transformed to optically active acetoxy-2-arylpropionic acid ethyl esters with 60-88% yields and 53-92% ee.     

Synthesis of methyl 3-bromomethylbut-3-enoate and its reactions with aldehydes and tributylchlorostannane in the presence of zinc

Methyl 3-bromomethylbut-3-enoate smoothly reacted with prenal, β-ionylideneacetaldehyde, benzyloxyacetaldehyde, and tributylchlorostannane in the presence of zinc and aqueous ammonium chloride in tetrahydrofuran to give the corresponding δ-hydroxy-β-methylidenecarboxylic acid esters. In the absence of ammonium chloride, satisfactory yields of the products were obtained only in the reactions with prenal and benzyloxyacetaldehyde; these reactions involved lactonization of intermediate δ-hydroxy-β-methylidenecarboxylic acid esters, and the double carbon-carbon bond migrated to the conjugated position with the lactone carbonyl group. The condensation of β-ionylideneacetaldehyde with methyl 3-bromomethylbut-3-enoate was successfully used to obtain isotretinoin. Initial methyl 3-bromomethylbut-3-enoate was synthesized in a good yield from readily accessible ethyl 3,3-diethoxypropionate via cyclopropanation with ethylmagnesium bromide in the presence of titanium tetra(isopropoxide), oxidation of the acetal moiety to ester, and cleavage of the cyclopropane ring in intermediate methyl (1-methylsulfonyloxycyclopropyl)acetate.     

Transformation of alkyl esters of 4-oxo-3-phenylthioalkanoic acids into substituted 4-phenylthio-2(5H)-furanones and 3-phenylthiofurans

When the solutions of methyl and ethyl esters of 4-oxo-3-phenylthioalkanoic acids are boiled in toluene in the presence of p-toluene sulfonic acid, substituted 4-phenylthio-2(5H)-furanones are formed in good yields. In the reaction with diisobutylaluminum hydride or organomagnesium compounds, the latter convert into the corresponding 3-phenylthiofurans.Translated from Khimiya Geterotsiklicheskikh Soedinenii, Vol. 24, No. 3, pp. 313–316, March, 1988.     

Efficient synthesis of 2,6-disubstituted-5-hydroxy-3-oxo-2,3-dihydro-pyridazine-4-carboxylic acid ethyl esters

A general procedure is described for the preparation of 6-substituted-5-hydroxy-3-oxo-2,3-dihydro-pyridazine-4-carboxylic acid ethyl esters (6-substituted-5-hydroxy-3(2H)-pyridazinone-4-carboxylic acid ethyl esters). These compounds are shown to undergo selective alkylation at the 2-position in moderate to good yields (19-77%) to afford 2,6-disubstituted-5-hydroxy-3-oxo-2,3-dihydro-pyridazine-4-carboxylic acid ethyl esters (2,6-disubstituted-5-hydroxy-3(2H)-pyridazinone-4-carboxylic acid ethyl esters).     

The synthesis of DL- and L-2-amino-3-fluorobutyric acid

DL- and L-Threonine were esterified to their methyl and ethyl esters which on treatment with sulfur tetrafluoride in anhydrous hydrogen fluoride gave DL- and L-methyl and ethyl 2-amino-3-fluorobutyrates, respectively. Both fluorinated esters afforded on hydrolysis DL- and L-2-amino-3-fluorobutyric acid, respectively.     

Identification of the nitrosation reaction products of alkyl esters of 1,2-benzisoxazole-3-acetic acid by chemical and crystallographic methods

The reaction between methyl or ethyl esters of 1, 2-benzisoxazole-3-acetic acid and iso-amyl nitrite is reported. The main product is identified as 4-(2′-hydroxyphenyl)furazan-3-carboxylic acid ( 4 ) by chemical and X-ray crystal structure analyses. The synthesis of esters of E- and Z-α-(hydroxyimino)-1, 2-benzisoxazole-3-acetic acid is also reported.     

The CGC enantiomer separation of 2-arylcarboxylic acid esters by using β-cyclodextrin derivatives as chiral stationary phases

Chiral 2-arylcarboxylic acid esters are important intermediates in preparation of enantioenriched 2-arylpropionic acids type Non-steroidal anti-inflammatory drugs (NSAIDs). Enantiomer separation of 2-arylcarboxylic acid esters is crucial for evaluation of the asymmetric synthesis efficiency and the enantiomer excess of chiral 2-arylcarboxylic acid derivatives. The capillary gas chromatography (CGC) enantiomer separation of 17 pairs of 2-arylcarboxylic acid esters enantiomers was conducted by using seven different β-cyclodextrin derivatives (CDs) as chiral stationary phases. It was found that for the 7 pairs of 2-phenylpropionates enantiomers, CDs with both alkyl and acyl substituents especially 2,6-di-O-pentyl-3-O-butyryl-β-cyclodextrin exhibited better enantiomer separation abilities than the other CDs examined. For the 7 pairs of 2-(4-substituted phenyl)propionates enantiomers, 2,3,6-tri-O-methyl-β-cyclodextrin possessed better enantiomer separation abilities than the other CDs. Among the 3 pairs of 2-phenylbutyrates enantiomers examined, only methyl 2-phenylbutyrate enantiomers could be separated by three CDs among the 7 CDs tested, while enantiomers of ethyl 2-phenylbutyrate and isopropyl 2-phenylbutyrate couldn't be separated by any of the 7 CDs tested. Besides the structures of CDs, the structures of 2-arylcarboxylic acid esters including different ester moieties, substituents of phenyl, and different carboxylic acids moieties in 2-arylcarboxylic acid esters also affected the enantiomer separation results greatly. The CGC enantiomer separation results of 2-arylcarboxylic acid esters on different CDs are useful for solving the enantiomer separation problem of 2-arylcarboxylic acid esters.     

Reaction of 2-dimethylaminomethylene-1,3-diones with dinucleophiles. X. synthesis of 5-substituted ethyl or methyl 4-isoxazolecarboxylates and methyl 4-(2,2-dimethyl-1-oxopropyl)-5-isoxazolecarboxylate

Reaction of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates with hydroxylamine hydrochloride in methanol solution afforded in high yields the relative esters of 5-substituted 4-isoxazolecarboxylic acids II . These esters were hydrolyzed generally with concentrated hydrochloric acid-acetic acid mixtures to the corresponding carboxylic acids in satisfactory yields. Ethyl or methyl esters II isomerized with sodium ethoxide or methoxide, respectively, to the corresponding esters or hemiesters of 2-cyano-3-oxoalkanoic acids generally in excellent to satisfactory yields. Reaction of methyl 5,5-dimethyl-3-dimethylaminomethylene-2,4-dioxohexanoate with hydroxylamine hydrochloride afforded in moderate yield methyl 4-(2,2-dimethyl-1-oxopropyl)-5-isoxazolecarboxylate, which was converted by acid hydrolysis as above to 4-t-butyl-4-hydroxyfuro[3,4-d]isoxazol-6-(4H)-one.     

2-Benzoyl-2-ethoxycarbonylvinyl-1 and 2-benzoylamino-2-methoxy-carbonylvinyl-1 as N-protecting groups in peptide synthesis. Their application in the synthesis of dehydropeptide derivatives containing N-terminal 3-heteroarylamino-2,3-dehydroalanine

Ethyl 2-benzoyl-3-dimethylaminopropenoate ( 6 ) and methyl 2-benzoylamino-3-dimethylaminopropenoate ( 46 ) were used as reagents for the protection of the amino group with 2-benzoyl-2-ethoxycarbonylvinyl-1 and 2-benzoylamino-2-methoxycarbonylvinyl groups in the peptide synthesis. Reactions of ethyl 2-benzoyl-3-dimethylaminopropenoate (6) with α-amino acids gave N-(2-benzoyl-2-ethoxycarbonylvinyl-1)-α-amino acids 13–19. These were coupled with various amino acid esters to form N-(2-benzoyl-2-ethoxycar-bonylvinyl-1)-protected dipeptide esters 20–31. The removal of 2-benzoyl-2-ethoxycarbonylvinyl-1 group, which was achieved by hydrazine monohydrochloride or hydroxylamine hydrochloride, afforded hydrochlo-rides of dipeptide esters 32–41 in high yields. Similarly, the substitution of the dimethylamino group in methyl 2-benzoylamino-3-dimethylaminopropenoate ( 46 ) by glycine gave N-(2-benzoylamino-2-methoxycar-bonylvinyl-1)glycine ( 47 ), which was coupled with glycine ethyl ester to give N-[N-(2-benzoylamino-2-methoxycarbonylvinyl-1)glycyl]glycine ethyl ester ( 48 ). Treatment of 48 with 2-arnino-4,6-dirnethylpyrimi-dine afforded N-[glycyl]glycine ethyl ester hydrochloride (34) in high yield. Amino acid esters and dipeptide esters were employed in the preparation of tri- 58-70, tetra- 71–82, and pentapeptide esters 83–85 containing N-terminal 3-heteroarylamino-2,3-dehydroalanine. 2-Chloro-4,6-dimethoxy-1,3,5-triazine was employed as a coupling reagent for the preparation of peptides 58–85.     

A New Convenient Synthesis of α-Arylpropionic Acid Esters and α-Arylpropionitriles

Various types of α-arylpropionic acid esters were effectively obtained by the coupling reaction of aryl Grignard reagents and α-bromopropionic acid esters in the presence of nickel catalysts. α-Arylpropionitriles, precursors of α-arylpropionic acids, were also synthesized by the reaction of α-methanesulfonyloxypropionitrile and arylcopper reagents prepared from equimolar amount of arylmagnesium halides and copper(I) bromide.     

Heck-mediated synthesis and photochemically induced cyclization of [2-(2-styrylphenyl)ethyl]carbamic acid ethyl esters and 2-styryl-benzoic acid methyl esters: total synthesis of naphtho[2,1f]isoquinolines (2-azachrysenes)

We describe two new closely related total syntheses of naphtho[2,1-f]isoquinolines. The first synthesis consists of a Heck coupling reaction between trifluoromethanesulfonic acid 2-(2-ethoxycarbonylaminoethyl)phenyl esters and styrenes to give [2-(2-styrylphenyl)ethyl]carbamic acid ethyl esters. These compounds cyclize to give (2-phenanthren-1-yl-ethyl)carbamic acid ethyl esters, from which 2-azachrysenes can be obtained in a three-step sequence. The second synthesis includes a new total synthesis of 2-styrylbenzoic acid methyl esters by Heck coupling of methyl o-iodobenzoates to styrenes, followed by the transformation of the resulting benzoic acid derivatives into phenanthrene-1-carboxylic acid methyl esters and then into the target compounds by a six-step sequence including a Bischler-Napieralski cyclization.     

Gas-phase reactivity of the O=P(OCH3)2 + phosphonium ion towards alpha,beta-unsaturated esters in a quadrupole ion trap

Ion-molecule reactions between the O=P(OCH3)2 + phosphonium ions and eight alpha,beta-unsaturated esters (methyl acrylate, ethyl acrylate, methyl crotonate, ethyl crotonate, methyl 3,3-dimethylacrylate, ethyl 3,3-dimethylacrylate, methyl methacrylate and ethyl methacrylate) were performed in a quadrupole ion trap mass spectrometer. The O=P(OCH3)2 + phosphonium ions, formed by electron ionization from neutral trimethyl phosphite, were found to react with alpha,beta-unsaturated esters to give an adduct [RR'C=CR'COOR', O=P(OCH3)2]+, which lose spontaneously a molecule of trimethyl phosphate (R'=CH3) or dimethyl ethyl phosphate (R'=C2H5). An ion corresponding to a protonated trialkyl phosphate is also observed when substituent R'=H. To confirm the experimental results, and to elucidate the mechanism for the formation of the ionic species, a theoretical study using the density functional theory (DFT) approach was carried out. The potential energy surface obtained from B3LYP/6-31G(d,p) calculations for the reaction between O=P(OCH3)2 + and methyl acrylate is described.     

Furan derivatives. Part 8 On substituent effects in the synthesis of 4,5-dihydro-3H-naphtho[1,8-bc]furans

4,5-Dihydro-3H-naphtho[1,8-bc]furans 4 and 6 which have various substituents (R¹ and R²) have been synthesized from 8-oxo-5,6,7,8-tetrahydro-1-naphthyloxyacetic acids 1 and 3 or their ethyl esters 2 . The reaction of acids 1 and 3 with sodium acetate in acetic anhydride gave a mixture of furans 4 and 6 and lactones 5 and 7 . The ratios of the products were varied according to the types of substituents (R¹ and R²) in acids 1 and 3 . As the substituent R¹ (R² = hydrogen) in acids 1 was changed from hydrogen to a methyl, ethyl or isopropyl group, production of furans 4 became more difficult. However, when a phenyl group was used as the substituent, furan 4 was obtained in good yield. Similarly, as the substituent R² (R¹ = hydrogen) in acids 1 was changed from hydrogen to a methyl, ethyl or isopropyl group, furan formation was more difficult. In contrast, acids 3 which had electron-withdrawing substituents such as chlorine, bromine or a nitro group at the 4-position afforded furans 6 in good yield. 4,5-Dihydro-3H-naphtho[1,8-bc]furans 4 and 4,5-dihydro-3H-naphtho[1,8-bc]furan-2-carbocylic acids 8 were synthesized from the reaction of esters 2 and potassium hydroxide in dioxane. When the substituents R¹ or R² in esters 2 were varied from hydrogen to a methyl, ethyl or isopropyl group the total yields of furans 4 and furancarboxylic acids 8 were reduced.     

Synthesis and antibacterial activity of 1-(substituted-benzyl)-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acids and their 6,8-difluoro analogs

Alkylation of 6,7-difluoro-4-hydroxyquinoline-3-carboxylic acid ethyl ester with substituted-benzyl chlorides gave 1-(substituted-benzyl)-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid ethyl esters. Their treatment with piperazine or N-methylpiperazine in pyridine yielded 1-(substituted-benzyl)-6-fluoro-1,4-dihydro-4-oxo-7-(l-piperazinyl)quinoline-3-carboxylic acid ethyl esters which were hydrolyzed with aqueous sodium hydroxide and then acidified with hydrochloric acid afforded the desired 1-(substituted-benzyl)-6-fluoro-1,4-dihydro-4-oxo-7-(1-iperazinyl)quinoline-3-carboxylic acids. The 6,8-difluoro analogs were prepared similarly using 6,7,8-trifluoro-4-hydroxyquinoline-3-carboxylic acid ethyl ester as a starting material. Some of these quinolones demonstrated fairly good antibacterial activities. Among them, 6-fluoro-1-(4-fluorophenylmethyl)-1,4-dihydro-7-(1-iperazinyl)-4-oxoquinoline-3-carboxylic acid ( 7d ) and 6,8-difluoro-1-(3-fluorophenylmethyl)-1,4-dihydro-7-(1-piperazinyl)-4-oxoquinoline-3-carboxylic acid ( 8c ) are two of the best.     

N-(5-氯-2-羟苯基)氨基酸酯的合成、表征及抑菌活性

以5-Cl水杨醛和L-苯丙氨酸、L-亮氨酸及L-甘氨酸的脂肪酸酯为原料,通过碱催化的席夫碱缩合反应,合成了6种N-（5-氯-2-羟苄基）席夫碱氨基酸酯及其还原产物N-（5-氯-2-羟苄基）氨基酸酯。 化合物的结构及组成经过IR、¹H NMR和元素分析测试技术进行了表征。 合成的席夫碱及其还原产物对革兰氏阴性菌、革兰氏阳性菌及真菌均有不同程度的抑制作用。 质量分数为0.01%的N-（5-氯-2-羟苄基）席夫碱氨基酸酯对大肠杆菌的抑菌率达90%以上,而N-（5-氯-2-羟苄基）氨基酸酯对金黄色葡萄球菌的抑菌率也在90%以上,均为强抑菌活性,其中N-（5-氯-2-羟苄基）苯丙氨酸酯的抑菌率达98%以上。     

Novel approach to the synthesis of 3-acyl substituted indolizines. The synthesis of 3-(indolizinyl-2)alanine and 4-(indolizinyl-3) homoalanine derivatives

A novel approach to the synthesis of 3-acylindolizines and the transformations of some acids into tryptophane analogues are described. Reaction of ethyl 2-pyridinylacetate and methyl 2-quinolinylacetate with N-trifluoroacetyl-5-bromo-4-oxonorvaline methylester led to N-trifluoroacetyl-3-(1-ethoxycarbonylindolizinyl-2) alanine methyl ester and N-trifluoroacetyl-3-(3-methoxycarbonylpyrrolo [1,2-a]quinolinyl-2) alanine methyl ester, respectively. Treatment of ethyl 2-pyridinylacetate and 2-pyridinylacetonitrile, first with N,N-dimethylformamide dimethyl acetal (DMFDMA), followed by reaction with phenacyl bromide, gave the corresponding 3-benzoylindolizines, while the reaction of ethyl 2-pyridinylacetate and 2-pyridinylacetonitrile with DMFDMA, followed by treatment with (S)-N-trifluoroacetyl-5-bromo-4-oxonorvaline methyl ester, gave the corresponding N-trifluoroacetyl-4-oxo-4-(indolizinyl-3)homoalanine methyl esters.     

Evaluation of animal liver acetone powders for the resolution of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

Butyl, ethyl and methyl esters of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid were hydrolyzed stereoselectively under very mild conditions to give the corresponding (S)-acid and the unreacted (R)-ester using readily available animal liver (chicken, mouse, rat and rabbit) acetone powders.     

Lanostanoids Isolated from Ganoderma lucidum Mycelium Cultured by Submerged Fermentation

Three new lanostane triterpene acids, 3‐O‐acetylganoderic acid B ( 1 ), 8β,9α‐dihydroganoderic acid C ( 3 ), and 3‐O‐acetylganoderic acid K ( 4 ), as well as two new lanostane triterpene acid ethyl esters, ethyl 3‐O‐acetylganoderate B ( 2 ) and ethyl ganoderate J ( 5 ), were isolated and characterized from Ganoderma lucidum mycelia which was cultured by submerged fermentation method. Their structures were elucidated on the basis of spectroscopic methods. In addition, the identification of two known lanostane triterpene acid methyl esters, methyl O‐acetyl ganoderate C and methyl 3,7,11,15,23‐pentaoxo‐lanost‐8‐en‐26‐oate were identified by comparison of the NMR data with those reported in the literature.     

Chlorotrimethylsilane promoted asymmetric Michael reaction of chiral enamines of α-alkyl β-keto esters

By the promotion of chlorotrimethylsilane, asymmetric Michael reaction of the chiral enamines (2) of α-alkyl β-keto esters (1) with methyl vinyl ketone and ethyl acrylate proceeded to afford, after hydrolysis, either enantiomer of the corresponding adducts (4) in a good enantioselectivity.