关键词： Alkenes/chemistry   Dopamine Agonists/chemical synthesis   Lithium/chemistry*   Nitro Compounds/chemistry   Organometallic Compounds/chemistry   Piperidines/chemical synthesis*   Quinolones/chemical synthesis*   Receptors, Dopamine D1/agonists   Stereoisomerism   Thiophenes/chemical synthesis*  

摘要： Chiral arene-fused-piperidine 1 is one of the representative structuralmotifs often observed in biologically active compounds such as naturally occurring phenanthridineand isoquinoline alkaloids as well as artificial pharmaceuticals. A straightforward synthetic waytoward 1 is the conjugate addition of 2-hydroxymethylaryllithiums 2 to nitroalkenes 3 and subsequentreduction of the nitro group to an amino group and cyclization to construct piperidine motifs 1(Figure 1). The first asymmetric alkyllithium addition to nitroalkenes was developed by themediation of a chiral ligand, giving the β-alkyl nitroalkanes in moderate enantioselectivity. Thecatalytic asymmetric additions of dialkylzinc and arylboronic acid were impressive recent ***, there have been only few that achieve asymmetric addition of 2-hydroxymethylaryl or itsequivalent nucleophiles to nitroalkenes. A spectacular exception was the sparteine-mediatedconjugate addition of the lithiated N-Boc allylic and benzylic amines to nitroalkenes, whichprovided an efficient way to the synthesis of simple piperidines in high enantioselectivities. Wedescribe the straightforward construction of chiral arene-fused-piperidines 1 by a highlyenantioselective addition of 2-trityloxymethylaryllithiums 2 (R = CPh_3) to cyclic and acyclicnitroalkenes 3. The versatility of the process was proven by the first asymmetric synthesis of adopamine D1 full agonist, A-86929 (20).

关键词： Enolates   Stereoselectivity   Carbonyls   Selectivity   Aldol reactions  

摘要： The dimer of methylketene can be conveniently prepared in one step and high enantiomeric excess from propionyl chloride, using a catalytic amount of a silylated cinchona alkaloid as a source of chirality. Opening of the dimer with a lithiated sulfonamide affords a beta-ketosulfonimide, which undergoes Sn(II)-mediated aldol reactions to diastereoselectively afford the anti,syn-aldol adduct. Alternatively, reduction of the dimer to the beta-hydroxy ketone, followed by acylation, affords a beta-acyloxyl ketone that undergoes diastereoselective, dialkylboron chloride-mediated aldol reactions to produce the anti,anti-aldol adduct.

关键词： Hydrocarbons   Aziridines   Enantioselective synthesis   Ethers   Molecular structure  

摘要： Unknown diaryl (1-3) and alkyl-phenyl (4, 5) N-tosyl aziridines have been successfully synthesized from pure (R,R,R,Ss)-(-)-sulfonium salt derived from Eliel's oxathiane, tosylimines 11a-f, and using a phosphazene base (EtP2) to generate the ylide. Both cis and trans aziridines have exceptionally high enantiomeric purities (98.7-99.9%). The (2R,3R)-configuration of trans-3 and the (2R,3S)-configuration of cis-4 have been determined by X-ray analysis using the Bijvoet method. The R-configuration found at C2 is consistent with the model and all previous results, therefore all trans-aziridines and cis-aziridines have been assigned the (2R,3R)- and the (2R,3S)-configurations, respectively. This two-step asymmetric synthesis can be easily used on gram quantities and involves no unstable/hazardous reagent. The chiral auxiliary is used in a stoichiometric amount but is recovered in high yield and reused.

关键词： Organic compounds  

摘要： The stereoisomers of 2-amino-5-carboxymethyl-cyclopentane-1-carboxylate may be prepared stereo selectively from diester derivatives of (E,E)-octa-2,6-diendioc acid, with the key step utilising the conjugate addition of homochiral lithium N-benzyl-N-alpha-methylbenzylamide. The trans-C(1)-C(2)-stereoisomers are readily prepared via a diastereoselective tandem conjugate addition cyclisation protocol with lithium (R)-N-benzyl-N-alpha-methylbenzylamide, with subsequent hydrogenolysis and ester hydrolysis giving the (1R,2R,5R)- and (1R,2R,5S)-beta-amino diacids in good yields. The preparation of the cis-C(1)-C(2)-stereoisomers utilises a protocol involving N-oxidation and Cope elimination of the major diastereoisomeric product arising from conjugate addition and cyclisation, giving homochiral (R)-5-carboxymethyl-cyclopentene-1-carboxylate. Conjugate addition of either lithium (R)- or (S)-N-benzyl-N-alpha-methylbenzylamide to (R)-5-carboxymethyl-cyclopentene-1-carboxylate, and diastereo selective protonation with 2,6-di-tert-butyl phenol gives, after hydrogenolysis and ester hydrolysis, the (1S,2R,5R)- and (1R,2S,5R)-beta-amino diacids in good yield. The use of (S)-N-benzyl-N-alpha-methylbenzylamide in the initial conjugate addition and cyclisation reaction, and subsequent repetition of the elimination and conjugate addition strategy allows stereoselective access to all stereoisomers of 2-amino-5-carboxymethyl-cyclopentane-1-carboxylate.

关键词： CATIONS   ETHER (Anesthetic)   GENE transfection   BIOSYNTHESIS   AMMONIUM salts   LIPIDS  

摘要： The cationic diether-linked cytofectin DOTMA (available commercially as a mixture, Lipofectin comprised of DOTMA:DOPE, 1:1) and analogues including DIMRIE and DORIE are frequently used for in vitro and in vivo transfections. Despite this wide usage direct synthetic routes to the optical isomers have received little attention to date. Here we describe strategies to synthesize enantiomers of DOTMA and analogues, including an extremely concise procedure to the trimethylammonium salts. One strategy utilized N-protection, as the imine, with concomitant ether formation and deprotection during the workup. Methylation of the 1-amino-2,3-dialkyloxypropane then generated the trimethylammonium cationic lipids directly. This methodology was extended to synthesize a novel headgroup functionalized lipid. A second route was also developed using an alternative chiral synthon.

关键词： aldol reaction   Thioglycolates   Quaternary   enolate   Asymmetric synthesis  

摘要： Reduction of alpha,alpha-disubstituted thioglycolate amides with lithium di-tert-butylbiphenylide affords alpha,alpha-disubstituted enolates with high Z/E selectivity. Transmetalation of the enolates with dicyclohexylboron bromide facilitates highly diastereoselective aldol reaction with aromatic and alpha,beta-unsaturated aldehydes.

关键词： 离子液体   不对称合成   有机化学反应   分类   制备   氢化反应   酰基化反应   环氧化反应   酶催化反应  

摘要： 离子液体作为溶剂已广泛应用于许多有机化学反应.总结了离子液体中的不对称有机反应,如氢化反应、酰基化反应、环氧化反应、酶催化反应等.

关键词： 氨基酸   叔亮氨酸   拆分   不对称合成   选择性酯化  

摘要： 氨基酸及其衍生物作为重要的化合物和有机药物中间体,广泛应用于医药、食品、饲料、化妆品、农业和化工等方面.本文研究了光学活性叔亮氨酸的合成和氨基酸的选择性酯化.一.光学活性叔亮氨酸的合成叔亮氨酸是一种非蛋白源的手性氨基酸,由于叔丁基的特殊结构和性质,是重要的医药中间体和不对称合成的手性诱导模板及催化剂.本文通过了两种方法合成光学活性叔亮氨酸.(一)DL-叔亮氨酸合成及化学拆分.研究了以片呐酮(1)为原料,通过碱性高锰酸钾氧化,相转移催化剂存在条件下,得到三甲基丙酮酸(2),与盐酸羟铵反应生成相应的肟(3),经锌粉/乙酸体系或H<,2>/Raney-Ni还原,得到DL-叔亮氨酸(DL-4).利用(+)-10-樟脑磺酸进行化学拆分,得到L-叔亮氨酸(L-4).研究了氧化步骤及还原步骤的最佳反应条件,探索了工业化生产的可能性.(二)不对称诱导合成光学活性叔亮氨酸.研究了以片呐酮氧化得到的酮酸(2)为原料,与手性L-或D-α-苯乙胺反应,引入手性中心,生成亚胺5,经不对称诱导还原后,再经甲酸铵氢解还原脱去乙苯,得到L或D-叔亮氨酸(L-或D-4).研究了亚胺5在不同条件下的还原反应,发现利用NaBH<,4>还原可以获得较高的e.e.值.二.氨基酸的选择性酯化.由于天门冬氨酸(7a)和谷氨酸(7b)各含有两个羧酸基,反应时选择性不好,需要选择性地将一个羧基叔丁酯化保护.研究了以天门冬氨酸(7a)或谷氨酸(7b)为原料,经过氯甲酸苄酯保护氨基,环化保护α-位羧基,在硫酸催化下与异丁烯反应生成叔丁酯10,然后在H<,2>-Pd/C下脱保护,得到天门冬氨酸-4-叔丁酯(11a)或谷氨酸-5-叔丁酯(11b).研究了微波促进下的环化反应,发现在微波条件下反应产率高,且只需很少量溶剂,简便、快速,纯度高.利用叔丁醇代替异丁烯合成叔丁酯,在浓硫酸和无水硫酸镁存在下进行反应,产率好、操作方便.

关键词： α-芳基丙酸   布洛芬   萘普生   不对称合成  

摘要： 对近年来α-芳基丙酸类非甾体抗炎药光学纯品不对称合成方法从傅氏烷基化、重排反应、α-位的甲基化反应、Sharpless反应、格氏交叉偶联反应、氢化反应、羰化反应、酶催化反应这八个方面进行了总结和概述(特别是(S)-萘普生的合成),从中反映近年来不对称合成的新趋势。

关键词： 3-甲基吡咯烷蚂蚁毒素   不对称合成   (s)-苹果酸   生物碱   吡咯烷   蚂蚁信息素  

摘要： 以(S) 苹果酸衍生出的(2S,3R) 3 甲基苹果酸二甲酯7为原料,经过氯代、自由基还原脱氯和酯基还原得到(R) 2 甲基 1,4丁二醇10,对映体纯度为79.7%ee.进而合成了蚂蚁信息素生物碱(R) Leptothoracine1和(R) N (2' 苯基乙基) 3 甲基吡咯烷2.