(2E,4S)-4-叔丁氧羰基氨基-5-[(3S)-2'-氧代-3'-吡咯烷基]-2-戊烯酸乙酯的立体选择性合成及绝对构型

在(2E,4S)-4-叔丁氧羰基氨基-5-[(3S)-2'-氧代-3'-吡咯烷基]-2-戊烯酸乙酯(1)已有立体选择性合成路线的基础上,对各步产物的光学纯度进行了严格的检验,研究了反应条件对这些产物光学纯度的影响,并利用单晶X射线衍射方法确定了该类化合物的绝对构型.     

Synthesis of analogs of 5(4)-aminoimidazole-4(5)-caeboxamide and purines

4(5)-Sulfonyl chlorides, which were converted to the corresponding sulfamoyl derivatives, were obtained from the amide and ethyl ester of 4(5)-mercaptoimidazole-5(4)-carboxylic acid by oxidative chlorination. The azide of 4(5)-sulfamoylimidazole-5(4)carboxylic acid was synthesized through 4(5)-sulfamoylimidazole-5(4)-carboxylhydrazide, and its conversion in various media to 5(4)-aminoimidazole-4(5)-sulfonamide derivatives and to 3,4-dihydro-3-oxoimidazo[4,5-e]-1,2,4-thiadiazine 1,1-dioxide was studied.See [1] for communication V.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1119–1122, August, 1976.     

5-(2’-羧乙基)-6-烷基-3,4-二氢吡喃酮的合成

吡喃酮是许多天然产物的结构单元,我们曾由4-异丁酰基庚二酸在过量醋酸酐及乙酰氯存在下回流得到7-氧代-8,8-二甲基-△~9-六氢香豆素.本文由二氰乙基-β-二酮进行酮解水解反应得到4-酰基庚二酸1_(a-c)。 在过量醋酸酐、乙酰氯存在下由1_a、1_c为底物进行反应没有得到双环的香豆素衍生物.其产物和单纯以乙酐为缩合剂时的产物2_a、2_c相同,产率分别为68％、63％。2_c可在硫酸铁催化     

Reaction of 2-Phenyl-4-(ethoxymethylene)-5(4H)-oxazolone with 3,4-Dithio-toluene in the Presence of Lewis Base

A convenient procedure for the synthesis of thiocoumarin by the condensation of 2-phenyl-4-(ethoxymethylene)-5-(4H)-oxazolone with 3,4-dithio-toluene in the presence of triethylamine is reported. Here, both thio groups are able to react with the carbonyl group to produce a mixture of isomeric products at ambient temperature. Only one of the isomers upon heating gives a new coumarin product.     

Synthesis of oligomers of trans-(4S,5R)-4-carboxybenzyl 5-methyl oxazolidin-2-one: an approach to new foldamers.

The synthesis of two oligomers containing three and four residues, respectively, of trans-(4S,5R)-4-carboxy 5-methyloxazolidin-2-ones is described. The monomer is obtained by starting from benzyl-N-Boc-(3R)-aminobutanoate, by cyclization into the corresponding trans-(2S,3R)-2-carboxybenzyl-3-methyl-N-Boc-aziridine and rearrangement of the product to trans-(4S,5R)-4-carboxybenzyl-5- methyloxazolidin-2-one, catalyzed by Sn(OTf)2. The oligomers are synthesized by activating the carboxy group as its pentaflourophenyl ester. The trimer and the tetramer are obtained in good yield, and their 1H NMR spectra suggest that these molecules fold in ordered structures, where the C-4 hydrogen of a ring is always close to the carbonyl of the next ring. This result shows that the 4-carboxy-5-substituted-oxazolidin-2-ones are a new class of pseudoprolines which fully control the formation of a Xaai-1-Proi peptide bond in the trans conformation and are complementary to the pseudoprolines obtained from cyclocondensation of cysteine, serine, or threonine and aldehydes or ketones, which strongly favor the Xaai-1-Proi peptide bond in the cis conformation.     

Asymmetric synthesis of (4R,5R)-cytoxazone and (4R,5S)-epi-cytoxazone

(4R,5R)-Cytoxazone has been prepared in four steps and in 61% overall yield and >98% ee. Conjugate addition of lithium (R)-N-benzyl-N-[small alpha]-methylbenzylamide to tert-butyl (E)-3-(p-methoxyphenyl)prop-2-enoate and subsequent in situ diastereoselective enolate oxidation with (+)-(camphorsulfonyl)oxaziridine gave tert-butyl (2R,3R,[small alpha]R)-2-hydroxy-3-(p-methoxyphenyl)-3-(N-benzyl-N-[small alpha]-methylbenzylamino)propanoate in >98% de. Subsequent N-benzyl deprotection to the primary [small beta]-amino ester via hydrogenolysis, oxazolidinone formation with C(2)-retention by treatment with diphosgene and chemoselective ester reduction furnishes (4R,5R)-cytoxazone. The synthesis of the C(5)-epimer, (4R,5S)-epi-cytoxazone in 44% overall yield, has also been completed via a protocol involving N-Boc protection of the primary [small beta]-amino ester, utilization of the N-Boc group to facilitate simultaneous C(2)-inversion and oxazolidinone formation, and subsequent reduction.     

2-甲硫基-4-羟基-5-嘧啶甲酸乙酯的工艺优化

以S-甲基异硫脲半硫酸盐和乙氧基亚甲基丙二酸二乙酯为主要原料,乙醇为溶剂,合成出2-甲硫基-4-羟基-5-嘧啶甲酸乙酯,研究了2-甲硫基-4-羟基-5-嘧啶甲酸乙酯的工艺优化,考察了投料比、反应温度、反应时间等因素对产率的影响。 获得较好的反应条件:n(C₂H₆N₂S·1/2H₂SO₄):n(C₁₀H₁₆O₅):n(NaOH)=1.2:1:1.8,在室温下缓慢滴加NaOH溶液,搅拌反应6 h,酸化得白色固体产物,产率为81.1%。产物结构经熔点测定仪、¹H NMR、ESI-MS、FT-IR等技术手段得到验证。     

Synthese von 4-Benzylthio- und 4-(Arylthio)-1,3-oxazol-5(2H)-onen

Synthesis of 4-(Benzylthio)-and 4-(Arylthio)-1,3-oxazole-5(2H)-ones Following a known procedure, 4-(benzylthio)-1,3-oxazol-5(2H)-one ( 4a ) was synthesized starting from sodium cyanodithioformate ( 1 ) and cyclohexanone (Scheme 1). The structure of the intermediate 4-(benzylthio)-1,3-thiazol-5(2H)-one ( 3a ) was established by X-ray crystallography. An alternative route was developed for the synthesis of 4-(arylthio)-1,3-oxazol-5(2H)-ones which are not accessible by the former reaction. Treatment of ethyl cyanoformate ( 5 ) with a thiophenol in the presence of catalytic amounts of Et₂NH and TiCl₄, followed by addition of a ketone and BF₃.Et₂O in a one-pot-reaction, gave 4f–i in low-to-fair yields (Scheme 3). Both synthetic pathways-complementary as for benzyl–S and aryl-S derivatives–seem to be limited with respect to variation of substituents of the ketone.     

Design, synthesis, and biological evaluation of a library of 1-(2-thiazolyl)-5-(trifluoromethyl)pyrazole-4-carboxamides

A library of 422 1-(2-thiazolyl)-5-(trifluoromethyl)pyrazole-4-carboxamides was prepared in five steps using solution-phase chemistry. The first step in the synthesis was the reaction of ethyl 2-ethoxymethylene-3-oxo-4,4,4-trifluorobutanoate with thiosemicarbazide, which is reported in the literature to afford a 1:1 mixture of ethyl 1-thiocarbamoyl-5-(trifluoromethyl)pyrazole-4-carboxylate and ethyl 1-thiocarbamoyl-3-(trifluoromethyl)pyrazole-4-carboxylate. We reassigned the structure of the product to be a single compound, ethyl 5-hydroxy-1-thiocarbamoyl-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazole-4-carboxylate. This common intermediate was diversified by reaction with 17 alpha-bromoketones affording, in two steps, 17 1-(2-thiazolyl)-5-(trifluoromethyl)pyrazole-4-carboxylic acids. Scavenger resins were used to facilitate formation and purification of up to 27 amides from each of these acids in the last step. In addition, the Curtius reaction was applied to 12 of the acids followed by quenching with alcohols to afford a 108-member carbamate library. Certain compounds in the two libraries were toxic to C. elegans.     

Synthesis of analogs of 5(4)-aminoimidazole-4(5)-carboxamide and purines

The corresponding 5(4)-mercaptoimidazoles, from which various 5(4)-mercaptoimidazole-4(5)-carboxylic acid derivatives were synthesized, were obtained from the amide and ethyl ester of 5-diazoimidazole-4-carboxylic acid by substitution of the diazo group. 5-Diazo-imidazole-4-hydroxamic acid does not undergo substitution with sodium disulfide but does undergo cyclization to 3-N-hydroxyimidazo[4,5-d]-1,2,3-triazin-4-one under these conditions. The kinetics of the cyclization of diazoimidazoles were studied, and the interrelationship between the structure and reactivity of the latter was examined.See [1] for communication III.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1550–1554, November, 1975.     

Facile Synthesis of Enantiomerically Pure 1-（5-Bromo-2-chlorophenyl）-1-（4-ethoxyphenyl）ethane

A facile 7-step procedure for the synthesis of enantiomerically pure 1-（5-bromo-2-chlorophenyl）-1-（4-ethoxyphenyl）ethanes[（R）-2 and（S）-2] that started from （5-bromo-2-chlorophenyl）（4-ethoxyphenyl）methanone 3 was developed.The key step was the resolution of 2-（5-bromo-2-chlorophenyl）-2-（4-ethoxyphenyl）acetic acid 6 by crystallizations of its L-and D-menthyl esters 7 and 8 from petroleum ether to give optically pure enantiomers 9 and 10,respectively.The absolute configurations of the products were unambiguously determined by single-crystal X-ray diffractions of four key intermediates,9,10,13 and 14.This procedure is characterized by inexpensiveness,scalability and ability to produce two individual enantiomers of a diarylethane with unambiguously determined absolute configurations and high enantiomeric purities.     

2,6-二(5-烷基水杨基)-4-烷基苯酚的合成

以自制的正构长链烷基酚为原料与多聚甲醛在碱性催化剂下进行羟甲基化反应,生成2,6-二羟甲基-4-烷基苯酚,再与另两分子烷基酚在固体超强酸催化下进行缩合反应生成2,6-二(5-烷基水杨基)-4-烷基苯酚,用核磁共振氢谱和碳谱、红外光谱和元素分析对产物进行了结构鉴定,探讨了催化剂、反应物料配比、反应时间等条件对产物产率的影响.另外根据上述反应路线,以工业品壬基酚和多聚甲醛为原料,经羟甲基化反应、缩合反应合成了2,6-二(5-壬基水杨基)-4-壬基苯酚.上述两种结果表明,选用SO24-/SnO2固体超强酸作催化剂,2,6-二羟甲基-4-烷基苯酚和烷基酚的配比为1:2,140℃反应2h,产率达到95%.     

Ring closure reaction of 4-(2-hydroxyanilino)-2-phenyl-5-pyrimidinecarboxylic acid with acetic anhydride. Synthesis of pyrimido[5,4-c] [1,5]benzoxazepin-5(11H)ones

Syntheses of 11-acety1-2-phenylpyrimido[5,4-c][1,5]benzoxazepin-5(11H)one ( 16a ) and analogs ( 16b,c, 22 ) were described. The reaction of 4-chloro-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester ( 7 ) with 2-aminophenol afforded 4-(2-hydroxyanilino)-2-phenyl-5-pyrimidine-carboxylic acid ethyl ester ( 8a ). The latter was also prepared by catalytic reduction of 4-(2-nitrophenoxy)-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester ( 9 ), which was obtained from 7 and 2-nitrophenol. Involvement of 4-(2-aminophenoxy)-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester ( 12a ) in this reduction as an intermediate was demonstrated by an independent synthesis of 12a and its subsequent rearrangement to 8a. Hydrolysis of 8a or 12a gave 4-(2-hydroxyanilino)-2-phenyl-5-pyrimidinecarboxylic acid ( 15a ). Reaction of 15a with acetic anhydride afforded 16a , the first member of a novel ring system, the pyrimido[5,4- c ][1,5]-benzoxazepin. Additional examples ( 16b,c ) were prepared similarly. The corresponding 11-ethyl derivative ( 22 ) was prepared in similar fashion, starting with 7 and 2-ethylaminophenol. A possible reaction mechanism for the formation of 16a-c from 15a-c and acetic anhydride was discussed.     

4-(Cyclic Amidino)phenols - Preparation and Use In A Diamidine Synthesis

The Pinner synthesis was applied to the preparation of 4-(cyclic amidino)phenols in high yields from readily available 4-hydroxybenzimidic acid methyl ester hydrochloride and diaminoalkanes. An alternative attempt was made to convert 4-(hydroxy)thiobenzamide to 4-(1,4,5,6-tetrahydro-5-hydroxy-2-pyrimidiyl)phenol. A procedure for the preparation of 3,6-bis(4-hydroxyphenyl)- 1,2,4,5-tetrazine is reported here. The syntheses of 2,4-bis[4-(4,5-dihydro-lH-imidazol-2-yl)phenoxy]pyrimidine and 2-chloro-4-[4-(4,5-dihydro-lH-imidazol-2-yl)- phenoxylpyrimidine exemplify the use of the title synthetic intermediates.     

电化学合成1, 4-双[2-(3, 4, 5-三甲氧基苯基)乙烯基]苯

1,4-双[2-(3,4,5-三甲氧基苯基]苯[简称HPV]采用有机电化学的方法合成,对合成的原理和方法进行研究和探讨,得到此化合物的三种异构体的淡黄色混合物,即含29.4%全顺式,44.7%顺-反式和25.9%全顺式。所得混合物熔点范围为103-155℃,总得率为92%。     

2-(5-甲基-2-苯基-4-噁唑基)乙醇的合成工艺改进

以L-天门冬氨酸为原料,经过β-甲酯化,苯甲酰化,Dak in-W est反应,环合和氢化铝锂还原等反应步骤,以36.1%的总收率得到抗糖尿病药物的重要中间体2-(5-甲基-2-苯基-4-噁唑基)乙醇.用浓硫酸取代三氯氧磷作为关环剂,简化了环合工艺和后处理操作.     

Recyclization of 5-carbethoxy-4-methyl-2-mercapto(amino,hydroxy) pyrimidines to give 5-acetyl-2-mercapto(amino,hydroxy)-4-hydroxypyrimidines

Conditions for the selective preparation of 5-carbethoxy-4-methyl-2-substituted pyrimidines or 5-acetyl-4-hydroxy-2-substituted pyrimidines by condensation of ethoxymethyleneacetoacetic ester with 1,3-binucleophiles are proposed. It is shown that under the influence of sodium ethoxide 5-carbethoxy-4-methyl-2-substituted pyrimidines undergo rearrangement to 5-acetyl-4-hydroxy-2-substituted pyrimidines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1558–1559, November, 1982.     

A facile synthesis of novel optically active R,R-2-(4-(2-(4-(5-chloro-3-halo-pyridin-2-yloxy)-phenoxy)-propionyloxy)-phenoxy)-propionic acid esters using cyanuric chloride as potential herbicide

A facile method for the synthesis of a new series of R,R-2-(4-(2-(4-(5-chloro-3-halopyridin-2-yloxy)-phenoxy)-propionyloxy)-phenoxy) -propionic acid ester derivatives containing a halo-substituted pyridine carrying two R,R chiral centers from(R)-2-(4- hydroxyphenoxy)propionic acid,halopyridines and alcohols using base/cyanuric chloride/catalyst system is reported.Their herbicidal activities against grass weeds and crops selectivity were evaluated.     

药物曲美布汀对映体在涂敷三(4-甲基苯甲酸)纤维素酯手性固定 相上的HPLC分 离

涂敷15%(wt)三(4-甲基苯甲酸)纤维素酯于大孔硅胶担体上,制备手性固定相,以此手性固定相作填料,湿法装填液相色谱柱,直接分离(±)-曲美布汀对映体。确定对映体在固定相与洗脱液之间分配的自由能变之差值、焓变之差值和熵变之差值,考察洗脱液正己烷-异丙醇(v/v)中异丙醇含量在色谱分离对映体性能方面的影响。当洗脱液中异丙醇含量增加时,对映体的容量因子逐渐降低,分离因子变化不大,分离度逐渐降低。