Photoenzymatic Hydrosulfonylation for the Stereoselective Synthesis of Chiral Sulfones

Chiral sulfones are recurrent motifs in pharmaceuticals and bioactive molecules. Although chemical methods have been developed to afford α- or β- chiral sulfones, these protocols rely heavily on the pre-synthesis of structurally complicated starting materials and chiral metal complexes. Herein, we described a photoenzymatic approach for the radical-mediated stereoselective hydrosulfonylation. Engineered variants of ene reductases provide efficient biocatalysts for this transformation, enabling to achieve a series of β-chiral sulfonyl compounds with high yields (up to 92 %) and excellent e.r. values (up to 99 : 1).     

A Simple Diastereoselective Synthesis of Chiral Nonracemic Aliphatic Amines

An efficient procedure has been developed for the diastereoselective synthesis of chiral aliphatic amines (diastereoisomeric excess >96%) from (1S)-N-(1-methylethylidene)-1-phenylethylamine, i.e., Schiff base derived from the simplest ketone (acetone) and (1S)-1-phenylethylamine. The procedure includes successive lithiation, alkylation, and reduction and is characterized by high regioselectivity in the formation of alkylated syn-Z-imines. Hydride reduction of the prochiral C=N bond in the latter gives mainly optically active aliphatic amines with R configuration. All reactions are performed as a one-pot process without isolation of intermediate products.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 6, 2005, pp. 827–831.Original Russian Text Copyright © 2005 by Grishina, Luk’yanenko, Borisenko.     

Synthesis, Reactions, and Anti-inflammatory Activity of Heterocyclic Systems Fused to a Thiophene Moiety Using Citrazinic Acid As Synthon

Summary. A series of pyridines, pyrimidinones, and oxazinones were synthesized as anti-inflammatory agents using citrazinic acid (2,6-dihydroxyisonicotinic acid) as a starting material. Acryloyl pyridine was treated with cyanothioacetamide to give cyano pyridine-thione, which was reacted with ethyl chloroacetate to yield the corresponding amino ester. The ester was hydrolysed to the sodium salt, which was treated with acetic anhydride to afford 2-methyloxazinone, which was treated with ammonium acetate to afford 2-methylpyrimidinone followed by methylation with methyl iodide to yield 2,3-dimethylpyrimidinone. In addition, the oxazinone derivative was reacted with aniline or hydrazine hydrate to give 3-phenyl- or 3-aminopyrimidinones. The latter reacted with thiophene-2-carboxaldehyde or phenylisothiocyanate to afford Schiff’s bases or thiosemicarbazides. 3-Aminopyrimidinone was treated with phthalic anhydride or 1,2,4,5-benzenetetracarboxylic acid dianhydride or toluene-3,5-diisocyanate to afford the corresponding imide, bis-imide, and bis-semicarbazide derivatives. The pharmacological screening showed that many of these compounds have good anti-inflammatory activity comparable to Prednisolone^? as reference drug.     

新型手性路易斯碱的合成及其在手性脂肪胺制备中的应用

以氯霉胺为原料,经两步缩合反应合成了一个新型手性路易斯碱——N-[(4S,5S)-4-(4-硝基苯基)-2-十一烷基-1,3-二噁烷烃-5-基]吡啶甲酰胺(3);以三氯硅烷为氢源,3为催化剂,2-十三烷酮与芳香胺原位生成的脂肪亚胺经氢化硅烷化反应合成了两个手性脂肪胺,收率高达95%,对映选择性最高为16%,其结构经1H NMR和13C NMR确证。结果表明:在该反应中,3具有较佳的催化活性,但立体选择性不佳。     

The Chiral Synthesis of Thiazole Amino Acid Enantiomers

An efficient modified Hantzsch reaction is described for the synthesis of optically pure thiazole amino acid derivatives from the corresponding amino acids. The method is exemplified by the synthesis of a derivative of L-(Gln)Thz, the novel chiral thiazole amino acid moiety of dolastatin 3. The Cotton effects of thiazole amino acids correlate well with the absolute stereochemistry of these compounds.     

手性磷酸催化剂在不对称合成中的应用

手性磷酸是2004年报道的一类具有新型结构的强酸性Bronsted酸催化剂,近几年来的研究取得了很大的进展,已经成为有机小分子催化剂的一个重要分支。手性磷酸在催化一系列亚胺的加成和还原反应比如Mannich、亚胺的氢转移、亚胺的膦酰化、Pictet-Spengler、 Strecker、aza-Diels-Alder、 Friedel-Craft和α-重氮酯的烷基化等反应时都表现出了非常好的催化活性和立体选择性。本文主要综述了手性磷酸催化剂应用于亚胺相关反应的研究进展。     

Arylidene Copolyether Sulfones. I. Synthesis and Characterization of Some New Copolyether Sulfones Containing Dibenzylidene Cyclopentanone Moieties

Abstract

New copolyether sulfones containing 2,5-bis(4-oxo-benzylidene)-cyclopentanone moieties were prepared in the conventional literature manner by condensing the dipotassium salts of 2,5-bis(4-hydroxyphenzyl- idene)cyclopentanone (I) and 2, 2-bis(4-hydroxyphenyl)propane (Bisphenol A, III) with 4,4′-dichlorodiphenyl sulfone (II), or by condensing the dipotassium salts of I with chlorine-terminated Bisphenol A-4,4′-di-chlorodiphenylsulfone copolymers (V). The resulting copolyether sulfones were confirmed by IR, viscometry, DSC measurements, thermooptical (TOA), and thermogravimetric analysis (TGA).     

Synthesis and Enzymatic Degradation of Aliphatic Polyesters Copolymerized with Trimesic Acid

Abstract

Network copolyesters were made from adipic acid and ethylene glycol with 10–40 mol% trimesic acid (Y). Prepolymers prepared by melt polycondensation were cast from dimethylformamide solution and postpolymerized at 260°C for various times to form a network. The degree of reaction (D _R), estimated from the infrared absorbance of hydroxyl and methylene groups, increased with increasing postpolymerization time and leveled out at about 90% after 4–6 hours. Heat distortion temperatures (T _h) measured by thermomechanical analysis increased greatly from ?83 to 48°C upon the incorporation of Y. Wide-angle x-ray diffraction patterns showed that the copolymer films are amorphous. Density, tensile strength, and Young's modulus decreased for the copolymers with 10–30 mol% Y, whereas they increased drastically for the copolymer with 40 mol% Y. The enzymatic degradation was estimated by the weight loss of the copolymer films in buffer solutions with a lipase at 37°C. The weight loss decreased remarkably with increasing Y and showed no weight loss for the copolymer with 40 mol% Y. On the other hand, the weight loss by alkali hydrolysis increased for the copolymers with 10 and 20 mol% Y, implying a difference in the degradation mechanism between enzymatic degradation and alkali hydrolysis.     

Studies On the Development of a New Chiral 2-Pyrrolidinone Synthon

Previous results from this laboratory have showed that N,O-dibenzylated malimide 1 is a versatile intermediate for the asymmetric synthesis of pyrrolidines, 2-pyrrolidinons and β-hydroxy-γ-amino acids^[1-4]. All the reactivities showed in synthon A have been exploited, in order to extend our studies on the (S)-malic acid-based synthetic methodology, we were interested to study the synthon B.To this end,sulfone 2 and 3,two the potential synthetic equivalent to synthon B, were prepared from malimide 1. Preliminary results showed that sulfone 2 indeed displayed the reactivity of synthon B.     

碘化亚铜/氨基酸催化的芳香胺合成反应——一个研究型综合设计实验

介绍一个研究型综合设计实验。该实验以溴苯与苄胺的反应为模板,根据影响反应的因素,筛选出一个最优化的反应条件,再将此条件用于反应物结构及取代基性质对反应影响的研究。要求学生根据实验数据和文献提出合理的反应机理。     

含氨基酸单元的手性主体的合成及手性识别研究

以L-丙氨酸和2,7-二萘酚为原料通过简单的方法合成了二种带有荧光基团萘的手性阴离子主体(1和2), 用红外光谱、质谱、元素分析、核磁共振氢谱及碳谱表征了它们的结构. 用荧光光谱及核磁共振氢谱研究了主体与二苯甲酰酒石酸阴离子的相互作用, 结果表明1, 2与D-或L-二苯甲酰酒石酸阴离子均形成1∶1的配合物, 主体1展现出良好的对二苯甲酰酒石酸阴离子对映选择性识别能力.     

烯丙基砜的合成与表征

以三种烯丙醇为起始原料 ,经溴代生成烯丙基溴 ,然后与无水苯亚磺酸钠发生亲核取代反应生成烯丙基砜。烯丙基溴与烯丙基砜在相转移催化下的偶联反应也可合成新的烯丙基砜。作者用这两种方法合成了六种烯丙基砜。初步探讨了反应温度 ,催化剂等对反应的影响。产物结构经IR ,1 HNMR等波谱分析确证。     

手性方酰化哒嗪衍生物的合成及荧光特性研究

以3,6-二甲酰基哒嗪和丙氨酸、α-氨基苯酚、方酸为原料合成了一种新的手性方酰化哒嗪胺衍生物, 利用IR, ¹H NMR及元素分析对其结构进行了表征, 并研究了金属离子对化合物的荧光性的影响. 结果表明, Cu^2＋, Ni^2＋等金属离子对化合物产生明显的荧光猝灭作用.     

砜类化合物合成研究进展

砜类化合物具有广谱的生物活性,广泛应用于化学、医药、农药、材料科学等领域。同时作为强吸电子基团,砜类化合物可以通过碱和亲电试剂反应延长碳链,因此该类化合物的合成方法引起了国内外研究人员的高度重视,本文结合国内外学者对这方面的相关研究,重点从硫醚氧化、磺酰氯的磺酰化和亚磺酸盐的偶联三个方面对近几年来砜类化合物合成方法进行了综述。     

手性γ-氨基酸:5-羟基-3-氨基环己基甲酸的不对称合成

以光学纯的(1S,5S)-5-叔丁氧羰基氨基-3-环己烯基甲酸为原料,经立体选择性地碘代内酯化、脱碘、醇解、水解、酯化5步反应首次合成了两个光学纯的γ-氨基酸衍生物——(1R,3S,5R)-5-羟基-3-叔丁氧羰基氨基环己基甲酸甲酯(总收率36.7%)和(1R,3S,5R)-5-羟基-3-叔丁氧羰基氨基环己基甲酸苄酯(总收率35.2%),其结构经1H NMR,13C NMR,IR和ESI-HR-MS确证。     

手性胺-质子酸催化剂在有机催化不对称合成中的应用

手性胺-质子酸是近年来发展起来的新型高效、高对映选择性的有机催化体系, 已成功应用于催化不对称Aldol反应、Michael加成反应、Diels-Alder反应和Strecker反应等许多重要的有机合成反应. 价廉易得的质子酸的引入不仅可促进活性中间体烯胺的生成, 并可通过形成的氢键稳定反应的过渡态, 从而显著提高该催化体系的催化活性和立体选择性. 对各类手性胺-质子酸催化剂在有机催化不对称合成反应中的应用、不对称诱导反应的机理、手性胺和质子酸的分子结构对其催化活性和不对称诱导活性的影响进行了评述.     

Stereoselective Synthesis of Diaminosuberic Acid Via a Chiral Alkynyl Oxazolidine

A novel, stereoselective synthesis of enantiomerically pure, N-protected diaminosuberic acid (6) is presented. The key step in the synthesis is the oxidative dimerization of the chiral alkynyl oxazolidine (2).     

A Novel Synthesis of Fused Heterocyclic Sulfones

The applicability and synthetic potency of the novel reagent diethyl 2‐aryl‐3‐phenylsulfonylpropen‐1,1‐dicarboxylate 3 is reported. Compound 3 proved to be a key precursor in heterocyclic sulfones syntheses. Chemical and spectroscopic evidence for the structure of the newly synthesized compounds are described.     

Enantioselective Synthesis of N-[(S)-Ethoxycarbonyl-3-phenylpropyl]-L-alanyl-L-proline from Chiral Synthon Prepared Enzymatically; A Practical Method for Large-Scale Synthesis

Efficient procedures have been developed for the stereospecific synthesis of Angiotensin-converting enzyme inhibitor, Enalapril. The starting material, (R)-2-hydroxy-4-phenylbutyronitrile, is prepared from lipase-catalyzed acetylation. This process is useful for multigram-scale synthesis.