关键词： asymmetric catalysis   Bronsted acids   hydrogen bonds   organocatalysis   protonation  

摘要： Asymmetric catalysis of organic reactions is one of the main research fieldsin chemistry. Although for many years asymmetric catalysis was conceptually linked to the use ofchiral transition-metal complexes, processes catalyzed by metal-free species have recently receivedsignificant attention. In many cases, the effectiveness of these catalysts relies on the formationof strictly oriented hydrogen bonds. The substrate(s) are then activated by noncovalentinteractions, and in this manner synthetically highly valuable enantioselective transformations arepossible by applying well-defined low-molecular-weight nonmetallic catalysts. A particularly elegantexample of this concept is the taddol-catalyzed asymmetric hetero-Diels-Alder reaction developed byRawal and co-workers. In this cycloaddition, a simple chiral alcohol complexes to a carbonyl group,thus accelerating the enantioselective C-C bond-forming process, which gives the cyclic productwith >92 % ee (Scheme 1).

关键词： asymmetric catalysis   Bronsted acids   catalysis design   cooperative effects   Lewis acids  

摘要： Lewis and Bronsted acids can be utilized as more-effective tools for chemicalreactions by sophisticated engineering (designer acids). The ultimate goal of such designer acidsis to form a combination of acids with higher reactivity, selectivity, and versatility than theindividual acid catalysts. One possible way to take advantage of such abilities may be to apply acombined acids system to the catalyst design. The concept of combined acids, which can be classifiedinto Bronsted acid assisted Lewis acid (BLA), Lewis acid assisted Lewis acid (LLA), Lewis acidassisted Bronsted acid (LBA), and Bronsted acid assisted Bronsted acid (BBA), can be a particularlyuseful tool for the design of asymmetric catalysis, because combining such acids will bring outtheir inherent reactivity by associative interaction, and also provide more-organized structuresthat allow an effective asymmetric environment.

关键词： peptidomimetic   arginine   lysine   aminopeptidase   non-natural amino acid   rational drug design  

摘要： A series of omega-bromo-2(S)-methyl acids has been synthesized as precursors of novel arginine (Arg), lysine (Lys), and mercapto analogues. These intermediates contain alpha-methyl groups and are designed to mask the N-terminal amine when incorporated in pharmaceutically relevant peptides.

关键词： MOLECULES   HELICENE   (SS)-2-(P-TOLYLSULFINYL)-1,4-BENZOQUINONE   CHIRALITY  

摘要： The efficient one-pot six-step domino process which occurs when (SS)-2-(p-tolylsulfinyl)-1,4-benzoquinone (1) reacts with 3,6-divinyl-1,2,7,8-tetrahydrophenanthrenes 2a-c allowed enantioselective access to [7] helicene bisquinones 3a-c with excellent optical purities (96 to >99% ee).

关键词： STEREOSELECTIVE-SYNTHESIS   AQUEOUS-MEDIA   TETRAHYDROFURANS   DIHYDROXYLATION   DERIVATIVES   ACID  

摘要： The development of an efficient asymmetric dihydroxylation of 1,6-dibromodiene afforded a chiral biselectrophilic diol that displayed highly useful reactivity in water, as demonstrated by a three-step, two-pot asymmetric synthesis of a highly functionalized tetrahydrofuran.

关键词： 手性催化剂   直接不对称羟醛反应   Baylis-Hillman 反应   不对称合成  

摘要： 一.手性有机小分子催化剂的合成及催化Baylis-Hillman 反应研究 以易得的氨基酸为原料,合成了催化剂1、2、3 和4,并用于催化Baylis-Hillman反应。以聚乙二醇(400)为溶剂,研究了催化剂1-4 的催化性能及结构和反应立体选择性之间的关系。其中催化剂2、3 和4 催化的反应产率最高达95%,催化剂3 催化的反应产物ee %达54.3%。 二.新型手性有机小分子催化剂的合成及催化直接不对称羟醛反应研究 1 以易得的羟基脯氨酸为原料,方便地合成了一种新的不对称羟醛反应的手性催化剂4R-(2,4,6-三甲基苯甲氧基)-S-脯氨酸5。以过量的丙酮作溶剂, 使用5 mol%该催化剂, 有效地催化了多种取代苯甲醛与丙酮间的不对称羟醛反应, 产率最高达91.0%, ee 最高达88.5%。 2 (S)-脯氨酸用苄氧羰基氯保护氨基后用混合酸酐法与羟胺偶合,得到N-[N-苯甲氧羰酰-(S)-脯氨酰]羟胺,催化氢解脱去保护基得N-[(S)-脯氨酰]羟胺6。该化合物对映选择性催化直接羟醛反应,产率最高达到90.0%,对映体过量最高达89.5。

关键词： ALPHA-AMINO-ACIDS   GLYCINE CATION EQUIVALENTS   CHIRAL RELAY AUXILIARY   STEREOSELECTIVE-SYNTHESIS   CARBONYL-COMPOUNDS   ORGANIC-SYNTHESIS   HIGH DIASTEREOSELECTIVITY   ELIMINATION-REDUCTION   ENZYMATIC-SYNTHESIS   BETA-ELIMINATION  

摘要： The highly diastereoselective samarium diiodide and D2O-promoted conjugate reduction of homochiral (E)- and (Z)-benzylidene and isobutylidene diketopiperazines (E)-5,7 and (Z)-6,8 has been demonstrated. This methodology allows the asymmetric synthesis of methyl (2S,3R)-dideuteriophenylalanine 27 in >= 95% de and >98% ee, and (2S,3R)- or (2S,3S)-dideuterioleucine-(S)-phenylalanine dipeptides 37 and 38 in moderate de, 66% and 74% respectively. A mechanism is proposed to account for this process.

关键词： aldehydes   aldol reaction   asymmetric catalysis   carbohydrates   hexoses  

摘要： The directed asymmetric assembly of simple achiral building blocks intostereochemically complex molecules like carbohydrates and polyketides has long been accomplished byenzymes in *** growing interest in glycobiology and the search for novel antibiotics has ledto increased activity in developing reaction designs and methods for the synthesis of sugars andpolyketides.

关键词： L-脯氨酸   D-脯氨酸   D-脯氨酰胺   氯甲酸苄酯   对甲基苯磺酰氯   消旋   不对称合成  

摘要： 脯氨酰胺是一种重要的五元环状氨基酸衍生物。D-脯氨酰胺(D-Prolinamide)作为一种重要的光学活性吡咯衍生物,无论是用作拆分剂和手性试剂,或作为手性中间体合成某些手性药物,其在各种不对称合成反应中都显示出了优良的不对称源性能。如在合成抗肿瘤药物铂化合物(CDDP)、促甲状腺释放剂(TRF),精神安定药(Remoxipride)、瑞莫比利(Neuroleptic)等药物中,都发挥了重要的作用。合成D-脯氨酰胺主要采用手性源技术合成,即以D-脯氨酸(D-Pro)为原料来合成。由于D-Pro难以从自然产品中大量获得,虽可通过化学拆分的方法制备,但由于拆分方法本身的限制,其最高理论收率只能达到50%,因此价格昂贵。 本文从经济角度出发,运用不对称转换的方法,以L-Pro为起始原料,以S-酒石酸作拆分剂,合成D-Pro。然后通过上保护基,氨化和脱保护基等反应最后得到D-脯氨酰胺。并对其合成工艺进行了优化。 另外,文章为了有可比性,还运用了两种保护基:氯甲酸苄酯和对甲基苯磺酰氯来保护氨基,并从最后合成结果来讨论这两种保护基的可行性。 由于在合成过程中,不可避免的触及不对称中心,发生消旋使产率下降甚至得不到产物,因此本文还研究了D-脯氨酰胺在不同温度、pH值、反应时间下对它的消旋的影响和脱羧机理,这对以后的工业化生产有着极其重要的意义。

摘要： The antioxidant and redox properties of L-ascorbic acid are closely associated with the electron rich 2, 3-enediol moiety of the molecule and therefore selective functionalization of the 2- and 3-OH groups is essential for the detailed structure-activity studies. Reactions of 5- and 6-OH protected ascorbic acid with electrophilic reagents exclusively produce the corresponding 3-O-alkylated products under mild basic conditions due to the high nucleophilicity of the C-3-OH. Based on the density functional theory (B3LYP) electron density calculations, a novel and general method was devised for the direct alkylation of the 2-OH group of ascorbic acid with complete regio- and chemo-selectivity. A complete spectroscopic analysis of two complementary series of 2- O-acetyl-3-O-alkyl and 2-O-alkyl-3- O-acetyl ascorbic acid derivatives was carried out to define their spectroscopic characteristics and to resolve common inconsistencies in the literature. The asymmetric approach to the synthesis of natural products or other biologically active compounds is impeded by low abundance of natural sources as well as a limited number of efficient synthetic methods. Nevertheless, carbohydrate-based systems such as the aldono-1,4-lactones (also known as aldono-γ-lactones) which generate a host of chiral compounds have been particularly rewarding in this respect. This study shows a practical approach using 5,6-O-isopropylidene-L-ascorbic acid (ketal of L-ascorbic acid) as a single common starting material for facile asymmetric synthesis of protected, optically pure and functionalized aldono-1,4-lactones derivatives, valuable in the synthesis of derivatives of various pharmacologically active agents for structure-activity studies. The practicality of this new approach is demonstrated by the convenient synthesis of a series of thermal Claisen-rearranged products of 5,6-O-isopropylidene-3-O-allyl-L-ascorbic acid and 5,6-O-isopropylidene-2-O-allyl-L-ascorbic acid as the corresponding 5,6-O-is