关键词： azomethine   Coupling reaction   porphyrins   DIPOLAROPHILE   Ruthenium   azomethine ylide   diazo-2   Cycloaddition Reaction   ylide   Asymmetric synthesis  

摘要： Chiral multifunctionalized pyrrolines have been synthesized by a ruthenium porphyrin catalyzed three-component coupling reaction. In a one-pot reaction, ruthenium porphyrins catalyzed in situ generation of chiral azomethine ylides from chiral diazo esters and imines. Asymmetric 1,3-dipolar cycloaddition reactions of the chiral azomethine ylides with dipolarophiles afforded the corresponding pyrrolines in good yields and high diastereoselectivity (up to 92% de).

关键词： ENANTIOMERS   ALKALOIDS   BENZALDEHYDE   HYDRAZONES   CARBONYL compounds   BIOSYNTHESIS  

摘要： The enantioselective synthesis of both enantiomers of tetrahydropalmatine (2) (ee = 98%), a natural alkaloid belonging to the tetrahydroprotoberberine family, is described. The key step of this total synthesis is based on our tandem 1,2-addition/ring-closure methodology employing lithiated methylbenzamide and benzaldehyde SAMP or RAMP hydrazones as substrates. An initial route was investigated for the formation of N- and 3-substituted dihydroisoquinolones starting from 2-substituted benzaldehyde SAMP hydrazones, but although high diastereoselectivity was achieved, only disappointing yields were obtained. In our subsequent synthetic strategy, 2,3-dimethoxy-6-methylbenzamide 6 and 3,4-dimethoxybenzaldehyde SAMP or RAMP hydrazone 19 gave the dihydroisoquinolones 20 in high diastereomeric purity (de >= 96%) and reasonable yield (54-55%), taking into account the complex functionalities established in one step. Cleavage of the N-N bond of the chiral auxiliary and reduction of the carbonyl group of the amide moiety were performed in the same step, and the resulting tetrahydroisoquinolines 22 (ee = 99%) were N-functionalized by treatment with various electrophiles to investigate the ring closure by Pummerer, Friedel-Crafts, and Pomeranz-Fritsch reactions. The Pummerer cyclization led to the formation of (S)-(-)-2 with slight racemization (ee = 89%), whereas the Friedel-Crafts reaction proved to be unsuccessful. Finally, Pomeranz-Fritsch-type cyclization afforded the desired title compound (R)-(+)-2 in excellent enantioselectivity in 9% overall yield over seven steps and after optimization of the last step (S)-(-)-2 in 17% overall yield.

关键词： synthesis   Asymmetric synthesis  

摘要： The ladybird alkaloid, (+)-hyperaspine, has been synthesized in a concise and highly stereoselective manner. The total synthesis was AM accomplished in six steps and 21% overall yield.

关键词： Reagents   Anions   Ligands   Stereoselectivity   Enantioselective synthesis  

摘要： The first catalytic asymmetric synthesis of 2-aryl-2,3-dihydro-4-quinolones has been developed by way of a rhodium-catalyzed 1,4-addition of arylzinc reagents to 4-quinolones. These 1,4-adducts can be obtained with high enantioselectivity by the use of (R)-binap as a ligand, and high yields are realized by conducting the reactions in the presence of chlorotrimethylsilane.

关键词： .triphosphine   stereoselectivity   diphenylphosphine   asymmetric oxidation   naphthylamine   chiral metal   dichloro complex   Template Induced   Mixed Phosphine-Phosphine   diastereomeric products   monooxidation  

摘要： The asymmetric hydrophosphination reaction of 1,1-bis(diphenylphosphino)ethene and diphenylphosphine promoted by a chiral organopalladium(II) complex derived from (S)-N,N-dimethyl-1-(l-naphthyl)ethylamine proceeded stereoselectively to generate an equilibrium mixture of four diastereomeric triphosphine palladium(II) template products in a ratio of 17:5:3:2. Alternatively, the direct coordination of 1,1,2-tris(diphenylphosphino)ethane to the chiral organopalladium template generated the same equilibrium mixture of diastereomeric products with the same stereoselectivity. Subsequent asymmetric oxidation of the diastereomeric template products with hydrogen peroxide proceeded stereoselectively to generate four diastereomeric monooxidation products in the ratio of 14:3:3:1. The effects of solvent, temperature, and alternative oxidizing agents were also studied. The naphthylamine auxiliary was removed chemoselectively from the template products by treatment with concentrated hydrochloric acid to form an enantiomerically enriched mixture of the corresponding dichloro complexes, which upon subsequent repeated recrystallization gave the predominant enantiomeric complex in its optically pure form. Further ligand displacement of the enantiomerically pure dichloro complex with aqueous cyanide liberated the free mixed phosphine-phosphine oxide ligand in quantitative yield.

关键词： 不对称合成技术   手性纯化合物   药物审批   手性催化反应   药物化学  

摘要： 近几年来能够获得上市的新化学实体当中，绝大部分都是手性纯化合物，以消旋体作为药物批准的惯例是一去不复返了，取而代之的是经过手性转换后以单一异构体形式推向市场。除非你有足够理由证明以单一异构体上市不切实际，如药物的化学立体中心在贮存期间或在体内自动发生相互转换，否则管理当局很可能会不允许它们以消旋体形式推向市场。

关键词： 甘氨酸   丝氨酸   席夫碱   不对称合成  

摘要： 采用甘氨酸席夫碱Ni(Ⅱ)复合物法不对称合成光学纯的D-和L-丝氨酸.以2-N-(N′-苄基)脯氨酰-氨基-二苯甲酮甘氨酸席夫碱Ni(Ⅱ)复合物与聚甲醛反应,生成2-N-(N′-苄基)脯氨酰-氨基-二苯甲酮丝氨酸席夫碱Ni(Ⅱ)复合物,经水解生成D-或L-丝氨酸,对映体过量值(e.e.)达到98%,重结晶后e.e.为99.5%,并对手性辅基2-N-(N′-苄基)脯氨酰-氨基-二苯甲酮进行了回收,回收率为85%～95%.

关键词： ALCOHOL-DEHYDROGENASE   REDUCTION  

摘要： An efficient whole cell biotransformation process using Lactobacillus kefir was developed for the asymmetric synthesis of tert-butyl (3R, 5S) 6-chloro-dihydroxyhexanoate, a chiral building block for the HMG-CoA reductase inhibitor. The effects of buffer concentration, temperature, pH and oxygen on the asymmetric reduction were investigated in batch reactions. Improvements in final product concentration and yields of 153% ( 120 mM) and 79% (0.85 mol/mol) with respect to the batch-process were achieved in an optimised fed-batch process. The pure substrate tert-butyl-6-chloro-3,5-dioxohexanoate was dispersed as microdroplets into the reaction system. This resulted in a space-time yield of 4.7 mmol l(-1) h(-1). A diastereomeric excess of > 99% was measured for (3R, 5S) and (3S, 5S) tertbutyl 6-chloro-dihydroxyhexanoate.

关键词： AMINES   ORGANIC compounds   CHEMICAL tests & reagents   MOLECULES   ASYMMETRY (Chemistry)   STEREOCHEMISTRY  

摘要： 2-[4-(tert-Butoxycarbonyl)piperazinyl]benzylidene-tert-butanesulfinamides underwent nucleophilic 1,2-addition with different organometallic reagents to give highly diastereomerically enriched adducts. X-ray crystallography of the resulting alpha-branched N-Boc-2-piperazinylbenzyl-tert-butanesulfinamides confirms different mechanisms depending on the organometallic reagent used. Differential deprotection of the N-Boc and the tert-butanesulfinamides was investigated, and the dehydration byproducts have been identified and characterized. To avoid the formation of byproducts in the acidic deprotection step, the N-tert-butanesulfinamide group was converted to the corresponding N-tert-butanesulfonamide (Bus), which allowed for clean orthogonal deprotection. The efficient synthesis and deprotection of the N-Boc-2-piperazinylbenzyl-tert-butanesulfinamides herein described constitutes an attractive method for extensive structure-activity studies in the search for novel ligands of the human melanocortin 4 receptor.

关键词： CYCLOPROPANE   ASYMMETRIC synthesis   CARBENES (Methylene compounds)   ENANTIOSELECTIVE catalysis   CHEMICAL reactions   ORGANIC compounds   ORGANIC chemistry  

摘要： A diastereo- and enantiospecific formation of tetrasubstituted cyclopropanecarbene complexes and cyclopropanecarboxylates from lithiated aryloxiranes andalpha,beta-unsaturated Fischer carbene complexes is described.