扁桃酸的拆分和手性扁桃酸的合成研究进展

综述了扁桃酸拆分和手性扁桃酸合成的研究进展,对非对映体盐结晶法、萃取法、色谱法、电泳法、酶催化法拆分消旋扁桃酸的原理、工艺和特点进行了评述,并介绍了生物转化法、电化学法和直接化学法合成手性扁桃酸的研究状况。其中非对映体盐结晶法是目前工业生产手性扁桃酸的重要方法,而生物转化法合成手性扁桃酸具有良好的工业应用前景。     

Inherently chiral calixarenes: synthesis, optical resolution, chiral recognition and asymmetric catalysis

Inherently chiral calixarenes, whose chirality is based on the absence of a planar symmetry or an inversion center in the molecules as a whole through the asymmetric array of several achiral groups upon the three-dimensional calix-skeletons, are challenging and attractive chiral molecules, because of their potential in supramolecular chemistry. The synthesis and optical resolution of all varieties of inherently chiral calixarenes are systematically discussed and classified, and their applications in chiral recognition and asymmetric catalysis are thoroughly illustrated in this review.     

l-薄荷醇的合成及手性拆分研究进展

阐述了l–薄荷醇的理化性质及其应用现状,介绍了最新的化学合成和拆分方法,其中着重介绍和探讨了以异戊二烯为原料合成l–薄荷醇的技术路线。同时,介绍了生物催化合成薄荷醇和手性拆分技术的研究进展和闭环机理,展望了其发展的前景。     

手性表面活性剂合成及应用进展

简要介绍了手性表面活性剂。重点综述了氨基酸型、葡萄糖苷型、松香型、酒石酸型和麻黄素型手性表面活性剂的合成,阐明了手性表面活性剂在立体选择性合成、手性化合物的分离(如药物分离)以及手性无机材料合成上的应用,最后对手性表面活性剂的应用前景进行了展望。     

不对称催化合成技术及其最新进展

综述了不对称催化合成技术的两种方法——化学不对称催化法和生物不对称催化法在合成手性药物、农药、香料和食品添加剂等方面的应用进展。     

生物催化技术在手性化合物合成中的应用

生物催化的手性合成是当今手性合成方法研究的热点和发展方向。本文综述了生物催化技术在手性化合物合成中的应用,并对其应用前景进行展望。     

手性Gemini表面活性剂的研究进展

回顾了近年来手性Gemini表面活性剂的合成和应用研究进展,按照天然手性源种类对其进行归纳和总结,阐述了酒石酸基、氨基酸基、糖基和松香基等手性Gemini表面活性剂合成方法的研究现状,并介绍了手性Gemini表面活性剂具有高表面活性、生物相容性、可生物降解性和立体选择性等特点。最后,指出了手性碳原子的立体构型对于手性Gemini表面活性剂自组装行为的影响还有待于进一步研究,展望了其在制备手性介孔材料、药物载体和胶束催化等领域的发展趋势。     

手性α-氨基酸的不对称合成

按合成方法综述了手性α-氨基酸的研究进展。简要介绍了手性拆分、L-氨基酸的高同系化、不对称烷基化、亚胺的不对称烷基化、脱氢氨基酸的不对称氢化等各种合成方法。对手性α-氨基酸合成的今后发展方向做了讨论。     

离子液体在生物催化制备手性化合物中的应用

介绍了离子液体的特性;同时对近几年报道的离子液体对酶及细胞活性影响的研究进行了归纳、总结和分析;详细介绍了近几年报道的有关离子液体在生物催化手性化合物合成中的应用情况,特别是对于水解酶和氧化还原酶催化的反应按反应的类型分别进行了归纳和分析。     

Biocatalytic synthesis of some chiral pharmaceutical intermediates by lipases

Chiral intermediates were prepared by biocatalytic processes for the chemical synthesis of three pharmaceutical drug candidates. These include (i) the synthesis of [(3R-cis)-3-(acetyloxy)-4-phenyl-2-azetidinone2 for the semi-synthesis of paclitaxel (taxol)5, an anticancer compound; (ii) synthesis of chiral (exo,exo)-7-oxabicyclo [2.2.1] heptane-2,3-dimenthanol monoacetate ester9 for the chemoenzymatic preparation of a thromboxane A₂ antagonist; (iii) the enzymatic synthesis ofS-(−) 3-benzylthio-2-methylpropanoic acid, a key chiral intermediate for the synthesis of antihypertensive drugs captopril10 or zofenopril13.     

普瑞巴林手性中间体的合成工艺研究

以异戊醛和丙二酸二乙酯为原料,经过Knoevenagel缩合反应,合成普瑞巴林中间体2-羧乙基-5-甲基-2-己烯酸乙酯(Ⅰ),再通过与氰化钠的加成反应,合成普瑞巴林中间体2-羧乙基-3-氰基-5-甲基己酸乙酯(Ⅱ),利用酶Lipoprime 50T进行生物拆分,得到普瑞巴林手性中间体(3S)-2-羧乙基-3-氰基-5-甲基己酸(Ⅲ),GC检测e.e.为99.0%。改进并优化合成工艺,Ⅰ收率由78%提高至88.5%,Ⅱ收率90%提高至99%。     

面包酵母在手性化合物不对称合成中的类型

药物分子的立体化学决定其生物活性，手性已成为药物研究的一个关键因素。利用微生物或酶催化的方法进行手性化合物的不对称合成已经成为一个极具吸引力的方向。综述了近年来利用面包酵母催化不对称合成手性化合物的研究进展，着重讨论了利用面包酵母可进行的多种手性试剂的催化合成的反应类型。     

手性双噁唑啉金属配合物催化的不对称合成

在简要介绍各种结构类型的手性双噁唑啉配体的基础上，总结了近期手性双噁唑啉金属配合物在不对称合成中的应用。     

Biocatalytic synthesis of chiral intermediates for antiviral and antihypertensive drugs

The chiral intermediate (1S,2R) [3-chloro-2-hydroxy-1-(phenylmethyl)propyl] carbamic acid, 1,1-dimethylethyl ester 2a was prepared for the total synthesis of a human immunodeficiency virus protease inhibitor, BMS-186318. The stereoselective reduction of (1S) [3-chloro-2-oxo-1(phenylmethyl)propyl] carbamic acid, 1,1-dimethylethyl ester 1 was carried out using microbial cultures, among which Streptomyces nodosus SC 13149 efficiently reduced 1 to 2a. A reaction yield of 80%, enantiomeric excess (e.e.) of 99.8%, and diastereomeric purity of 99% were obtained for chiral alcohol 2a. Chiral l-6-hydroxy norleucine 3, an intermediate in the synthesis of antihypertensive drug, was prepared by reductive amination of 2-keto-6-hydroxyhexanoic acid 4 using beef liver glutamate dehydrogenase. The cofactor NADH required for this reaction was regenerated using glucose dehydrogenase from Bacillus sp. A reaction yield of 80% and e.e. of 99.5% were obtained for l-6-hydroxynorleucine 3. To avoid the lengthy chemical synthesis of the ketoacid, a second route was developed in which racemic 6-hydroxynorleucine [readily available from hydrolysis of 5-(4-hydroxybutyl) hydantoin 5] was treated with d-amino acid oxidase from Trigonopsis variabilis to selectively convert the d-isomer of racemic 6-hydroxynorleucine to 2-keto-6-hydroxyhexanoic acid 4 and l-6-hydroxynorleucine 3. Subsequently, the 2-keto-6-hydroxyhexanoic acid 4 was converted to l-6-hydroxynorleucine by reductive amination using glutamate dehydrogenase. A reaction yield of 98% and an e.e. of 99.5% were obtained.     

氯吡格雷生产技术研究进展

氯吡格雷早期的生产方法主要为外消旋对映体的拆分法,近年来发展了多种利用手性砌块进行不对称合成的技术。对氯吡格雷生产技术进行了介绍,并比较了各种生产技术的优缺点。     

樟脑衍生的新手性氨基醇的合成

天然（＋）．樟脑经磺酸化、磺酰氯化和氧化得到（1S）-7，7-二甲基双环[2．2．1]庚烷-1-羧酸-2-酮（2）。化合物2与二氯亚砜反应得到酰氯，继而与氨水反应得到（1S）-7，7-二甲基双环[2．2．1]庚烷-1．酰胺-2-酮（3）；以硼氢化钠还原化合物3得（1S，2R）-2-羟基-7，7-二甲基双环[2．2．1]庚烷-1-酰胺（4）；以四氢铝锂还原化合物4得新手性氨基醇（1S，2R）-1-氨基甲基-2-羟基-7，7-二甲基双环[2．2．1]庚烷。     

合成冰片中差向异构体的拆分

研究了合成冰片中异构体拆分的新方法.以合成冰片为原料,根据不同构型异构体与酸酐进行酯化反应能力的差异合成其酯化物.利用手性拆分剂对该酯化物进行拆分,通过手性液相分析各组分比例.拆分结果显示,龙脑含量从60.0％提高至90.6％,对合成冰片中龙脑与异龙脑的分离有显著效果.     

水解动力学拆分合成手性环氧氯丙烷用催化剂研究

水解动力学拆分是目前合成手性环氧氯丙烷的有效方法。salen催化剂的应用使得该反应得到的手性环氧氯丙烷产率高且具有高光学纯度,因此,关于salen催化剂的研究得到广泛关注。综述了合适salen催化剂的研究发现和完善过程,提出了引入价廉、具有高催化活性和高重复利用性的催化剂仍是当前乃至今后该领域研究工作的重点。     

Amino acid oxidase‐catalysed resolution and Pictet–Spengler reaction towards chiral and rigid unnatural amino acids

BACKGROUND: The biosynthesis of structurally complex isoquinoline alkaloids and other natural products occurs via aromatic amino acids such as tyrosine, and chiral and rigid amino acids. These structures are also key building blocks of many active pharmaceutical ingredients. The aim of this work was the exploration of a rapid and straightforward route to chiral 6‐hydroxy‐1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid. RESULTS: The preparation of (S)‐meta‐tyrosine from racemic meta‐tyro‐ sine with aminoacidoxidase has been developed with ee > 99% and 88% yield. The combination of this resolution with a subsequent Pictet–Spengler reaction enables straightforward and versatile access to chiral (S)‐6‐hydroxy‐1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid in 30% yield. CONCLUSIONS: This new short chemoenzymatic route to (S)‐6‐hydroxy‐1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid from commercially available DL‐m‐tyrosine is more convenient than other chemical procedures and establishes a new link between the pool of easily accessible racemic aromatic amino acids and the corresponding chiral rigidified amino acids, which are of interest as structural elements of many active pharmaceutical ingredients. These results facilitate synthetic access to a range of active pharmaceutical ingredients and metabolites in chiral form from the oxidation of amino acids. This advances the opportunities to study the molecular interactions with enzymes, receptors and effectors more precisely than with the racemic forms. Copyright © 2007 Society of Chemical Industry     

Biocatalytic synthesis of some chiral drug intermediates by oxidoreductases

Chiral intermediates were prepared by biocatalytic processes with oxidoreductases for the chemical synthesis of some pharmaceutical drug candidates. These include: (i) the microbial reduction of 1-(4-fluorophenyl)-4-[4-(5-fluoro-2-pyrimidinyl)-1-piperazinyl]-1-butanone (1) to R-(+)-1-(4-fluorophenyl)-4-[4-(5-fluoro-2-pyrimidinyl)-1-piperazinyl]-1-butanol (2) [R-(+)-BMY 14802], an antipsychotic agent; (ii) the reduction of N-4-(1-oxo-2-chloroacetyl ethyl) phenyl methane sulfonamide (3) to the corresponding chiral alcohol (4), an intermediate for d-(+)-N-4-{1-hydroxy-2-[(-methylethyl)amino]ethyl}phenyl methanesulfonamide [d-(+) sotalol], a β-blocker with class III antiarrhythmic properties; (iii) biotransformation of Nɛ-carbobenzoxy (CBZ)-l-lysine (7) to Nɛ-CBZ-l-oxylysine (5), an intermediate needed for synthesis of (S)-1-[6-amino-2-{[hydroxy(4-phenylbutyl)phosphinyl]oxy}1-oxohexyl]-l-proline (ceronapril), a new angiotensin converting enzyme inhibitor (6) and (iv) enzymatic synthesis of l-β-hydroxyvaline (9) from α-keto-β-hydroxyisovalerate (16). l-β-Hydroxyvaline (9) is a key chiral intermediate needed for the synthesis of S-(Z)-{[1-(2-amino-4-thiazolyl)-2-{[2,2-dimethyl-4-oxo-1-(sulfooxy)-3-azetidinyl] amino}-2-oxoethylidene]amino}oxyacetic acid (tigemonam) (10), an orally active monobactam.