内-α-甲基-α-取代双环[2·2·2]-5-辛烯(辛烷)-2-基甲醇的合成及香气

合成了内 -α-甲基 -α-取代双环 [2· 2· 2 ]-5 -辛烯 -2 -基甲醇和内 a-甲基 -α-取代双环 [2· 2· 2 ]辛烷 -2 -基甲醇共 2 0个化合物 ,其中 1 8个未见报道。通过 IR、1HNMR、对 MS碎片解析并配合气相色谱测定纯度确证了它们的结构 ,请评香专家评定了它们的香气 ,并讨论了化合物结构和香气之间的关系。     

SpinPHOX/Ir(Ⅰ)催化的2-羟甲基-3-芳基丙烯酸的不对称氢化

光学活性的2-羟甲基-3-芳基丙酸类化合物是许多手性药物的关键合成中间体,但到目前为止其不对称合成方法大多存在对映选择性不高及/或底物范围有限等问题.报道了手性SpinPHOX/Ir(I)络合物在一系列2-羟甲基-3-芳基丙烯酸的不对称氢化中表现出优良的催化性能,取得完全的底物转化和良好到优秀的对映选择性(高达95%ee).对于同一2-羟甲基-3-芳基丙烯酸底物的不对称氢化,使用中心手性相同但螺环骨架上的轴手性相反的催化剂分别以优良的对映选择性获得构型相反的产物,从而为光学活性2-羟甲基-3-芳基丙酸及相关手性药物的不对称合成提供了一条简便高效的途径.     

1-[(乙氧基)甲基]-6-(1-萘甲基)胸腺嘧啶的合成

HEPT是抑制HIV-1逆转录酶的潜在活性化合物。1-[(乙氧基)甲基]-6-(1-萘甲基)胸腺嘧啶是HEPT的类似物,通过增加6位取代基的位阻可提高药效。文献设计并合成了该化合物,并对关键中间体(d)的合成及脱羟基反应作了初步讨论。     

Myceliothermophin E片断(Z)-5-(2-甲基亚丙基)-3-吡咯啉-2-酮的合成及其 Baylis-Hillman 模型反应

采用两种方法合成了天然产物Myceliothermophin E片断(Z)-5-(2-甲基亚丙基)-3-吡咯啉-2-酮(1).方法一是以链状化合物为原料通过改良的HWE反应制备顺式α,β-不饱和酯；再经分子内亲核取代反应进行环合、消除反应制得1；方法二则以吡咯为原料,经Mukaiyama Aldol反应引入C5-位取代基,再经过消除反应制得1.(E)-11(合成1的中间体)与无水乙醛进行Baylis-HiUman反应,为Myceliothermophin E的全合成提供了一个可能的模型反应.     

内-α-取代-α-甲基双环[2,2,1]庚烷-2-基甲醇的合成及其结构与香气的关系

合成了18种内-α-取代-α-甲基双环[2,2,1]庚烷-2-基甲醇(Ⅰ)。测定了所有化合物的折光率(或熔点)、质谱、红外光谱、~1H核磁共振谱、气相色谱的保留时间和薄层色谱的比移值。评定了它们的香气,并与相应的内-α-取代-α-甲基双环[2,2,1]-5-庚烯-2-基甲醇(Ⅱ)系列化合物的香气进行了比较,初步探讨了结构与香气的关系。     

2-(5-取代苯氧甲基-1,3,4-噻二唑-2-亚胺基)-5-(取代苯基亚甲基)-4- 噻唑啉酮的合成

以2-氨基-5-取代苯氧甲基-1,3,4-噻二唑(1)为起始原料, 合成了中间体2-氯乙酰氨基-5-取代苯氧甲基-1,3,4-噻二唑)-2-乙酰亚胺(2)和2-(5-取代苯氧甲基-1,3,4-噻二唑-2-亚胺基)-4-噻唑啉酮(3), 化合物3进一步与取代苯甲醛发生类Knoevenagle缩合反应, 得到了一系列2-(5-取代苯氧甲基-1,3,4-噻二唑-2-亚胺基)-5-(取代苯基亚甲基)-4-噻唑啉酮类化合物4a～4p. 目标化合物4a～4p的结构经IR, ¹H NMR和元素分析确证.     

以(+)-樟脑缩苄胺作中间体对映选择合成(R)-α-取代苄胺

本文报道以(+)-樟脑作手性助剂, 苄胺为原料, 二者缩合制得的酮亚胺作中间体3,不对称合成(R)-α-取代苄胺(7)的一条有效新途径。化合物3用丁基锂去质子化提供的锂衍生物4和卤代烷反应, 以较高立体选择性产生烷基化产物6, 化合物6用醋酸羟胺转氨反应后, 获得了光学产率为4.6-90%的(R)-α-取代苄胺(7), 以肟的形式回收(+)-樟脑。     

6-亚甲基-17α-乙酰氧基-18-甲基-19-失碳-孕甾-4-烯-3,20-二酮的合成新方法研究

报道了16-亚甲基-17α-乙酰氧基-18-甲基-19-失碳-孕甾-4-烯-3,20-二酮的新合成方法. 以左旋18-甲基炔诺酮为原料, 通过脱水、氧化、环合、热解、环氧化、开环氧环、水解七步反应合成了目标化合物, 总收率20.0%. 其中化合物12, 13, 14, 15, 16尚未见文献报道.     

4α-甲基-5α-胆甾烷的合成及中间体立体化研究

4-甲基甾烷类化合物是一类广泛存在于原油、油页岩中的生物标志化合物。4α-甲基-5α-胆甾烷(4)的合成已有文献报道。我们用与     

二[1-甲基-4-(1-甲基-4-硝基吡咯-2-酰胺基)吡咯-2-酰胺基乙基]胺的合成与表征

报道了一种对称平行的多酰胺分子——二[1-甲基-4-(1-甲基-4-硝基吡咯-2-酰胺基)吡咯-2-酰胺基乙基]胺的合成方法, 以期对DNA序列进行新的特异性识别和切割, 从而研制新型有效的工具酶或抗癌药物. 合成方法简便易行、耗时短、不需过柱分离, 每步合成都有较高产率.     

Asymmetric synthesis of α,β-diamino acid derivates via Mannich-type reactions of a chiral Ni(II) complex of glycine with N-tosyl imines

A practical procedure composed of an asymmetric Mannich-type reaction between N-tosyl imine and a Ni(II) complex of glycine with (R)-o-[N-(N-benzylprolyl)amino]bezaophenone (BPB) as a chiral auxiliary catalyzed by Et(3)N in DMF to (R,2R,3S)-complexes, and decomposition of products with HCl to offer syn-(2R,3S)-α,β-diamino acids, was developed. Stereochemical mechanism of the Mannich reaction was proposed and supported by determining the absolute configuration of the product of the Mannich reaction relying on X-ray analysis. This two-step approach to amino acids was a general method and adapted to large-scale preparation.     

Enantioselective synthesis of (R)- and (S)-alpha-alkylcysteines via phase-transfer catalytic alkylation

We reported efficient enantioselective synthetic methodologies for (R)-alpha-alkylcysteines and (S)-alpha-alkylcysteines. The phase-transfer catalytic alkylation of 2-phenyl-2-thiazoline-4-carboxylic acid tert-butyl ester and 2-o-biphenyl-2-thiazoline-4-carboxylic acid tert-butyl ester, in the presence of chiral catalysts (1 or 2), gave the corresponding alkylated products, which could be hydrolyzed to provide (R)-alpha-alkylcysteines (67->99% ee) and (S)-alpha-alkylcysteines (66-88% ee), respectively.     

Synthesis of nonracemic polysubstituted cyclohexanes through cascade reactions of (2R,3S)-2-Acetyl-3-aryl-4-nitrobutanoates, adducts of Ni(II)-catalyzed michael addition

Stereoselective synthesis of ethyl-4,6-diaryl-2-hydroxy-2-methyl-5-nitro-3-formylcyclohexanecarboxylates was described. The formation of the asymmetric site of the required configuration is achieved by an enantioselective Michael addition of ethyl acetoacetate to nitroalkenes in the presence of a chiral Ni(II) complex with (R,R)-N,N′-dibenzylcyclohexane-1,2-diamine. Further reaction of the products obtained with cinnamic aldehyde led to the formation of polysubstituted cyclohexanes.     

Phase-transfer enantioselective monoalkylation of prochiral nickel(ii) complexes catalyzed by 3,3′-bis[hydroxy(diphenyl)methyl]-1,1′-binaphthyl-2,23′-diol (BIMBOL) as a route to α-amino acids

An achiral nickel complex with a Schiff base derived from glycine was alkylated with alkyl halides under conditions of asymmetric phase-transfer catalysis. The chiral tetraol (R)-BIMBOL was employed as a catalyst. The enantiomeric purity of the alkylation products was up to 88%. Subsequent decomposition of the complexes afforded the corresponding a-amino acids.     

A Facile Circular Dichroism Protocol for Rapid Determination of Enantiomeric Excess and Concentration of Chiral Primary Amines

A protocol for the rapid determination of the absolute configuration and enantiomeric excess (ee) of α‐chiral primary amines with potential applications in asymmetric reaction discovery has been developed. The protocol requires derivatization of α‐chiral primary amines through condensation with pyridine carboxaldehyde to quantitatively yield the corresponding imine. The Cu^I complex with 2,2′‐bis (diphenylphosphino)‐1,1′‐dinaphthyl (BINAP? Cu^I) with the imine yields a metal‐to‐ligand charge‐transfer (MLCT) band in the visible region of the circular dichroism (CD) spectrum upon binding. Diastereomeric host–guest complexes give CD signals of the same signs but different amplitudes, allowing for differentiation of enantiomers. Processing the primary optical data from the CD spectrum with linear discriminant analysis (LDA) allows for the determination of the absolute configuration and identification of the amines, and processing with a supervised multilayer perceptron artificial neural network (MLP‐ANN) allows for the simultaneous determination of the ee and concentration. The primary optical data necessary to determine the ee of unknown samples is obtained in two minutes per sample. To demonstrate the utility of the protocol in asymmetric reaction discovery, the ee values and concentrations for an asymmetric metal‐catalyzed reaction are determined. The potential of the application of this protocol in high‐throughput screening (HTS) of ee is discussed.     

Anomalous stereochemistry of pyrazolato-3,5-dicarboxylato-bridged dinuclear chromate(III) complexes containing ethylenediamine-N,N'-dicarboxylates with entrapped unstable conformations: X-ray structure of Na[Cr2(eddp)(mu-pzdc)].6H2O

Several new pyrazolato-3,5-dicarboxylato (pzdc) bridged dinuclear chromate(III) complexes containing linear tetradentate O-N-N-O type ligands were synthesized and structurally characterized. Among them, the X-ray structure of the eddp complex Na[Cr2(eddp)(mu-pzdc)].6H2O (eddp = ethylenediamine-N,N'-dipropionate) was determined to have a (sym-cis)-(unsym-cis) geometrical configuration with intramolecular three-center hydrogen bonds, entrapping the unfavored sym-cis configuration for the Cr(eddp) moiety as well as the favored unsym-cis one. As a pair of positional disorders, there were also found to be two conformational isomers with respect to the absolute configurations of the coordinated asymmetric nitrogen atom at the G (in-plane) ring for the unsym-cis moiety. Moreover, chiral pzdc-bridged dinuclear complexes with another type of O-N-N-O ligand, 1,2-cyclohexanediamine-N,N'-diacetate (cdda), were successfully synthesized, isolated, and characterized by column chromatographic behavior, elemental analysis, and chiroptical spectra. There were two diastereomers for Na[(R,R-cdda)Cr(mu-pzdc)Cr(S,S-cdda)] and only one isomer for Na[(R,R-cdda)Cr(mu-pzdc)Cr(R,S-cdda)] and Na[(R,R-cdda)Cr(mu-pzdc)Cr(edda)] (R,R- or S,S- and R,S-cdda = R,R-trans- or S,S-trans- and R,S-cis-1,2-cyclohexanediamine-N,N'-diacetate, and edda = ethylenediamine-N,N'-diacetate). From their circular dichroism (CD) spectra, these complexes could exhibit the delta-delta absolute configuration with ((sym-cis-R,R-cdda)-(unsym-cis-edda or S,S- or R,S-cdda)) geometrical configuration, indicating the abnormal eq-eq (N-Ceq) configuration for the R,R-cdda. The comparison among the CD spectra of the ((cdda)-(cdda)) complexes revealed that two diastereomers of the ((R,R-cdda)-(S,S-cdda)) complex correspond to the conformational isomers resulting from the difference in geometrical orientations of the secondary amine protons on two coordinated asymmetric nitrogen atoms with the opposite absolute configuration in the unsym-cis-S,S-cdda moiety. In a series of the pzdc-bridged Cr(III) complexes the anomalous conformations in two different geometrical configurations could be entrapped probably owing to stereognostic coordination through the intramolecular N-H...O hydrogen bond interaction.     

Asymmetric PTC C-alkylation catalyzed by chiral derivatives of tartaric acid and aminophenols. Synthesis Of (R)- and (S)-alpha-methyl amino acids

A new type of efficient chiral catalyst has been elaborated for asymmetric C-alkylation of CH acids under PTC conditions. Sodium alkoxides formed from chiral derivatives of tartaric acid and aminophenols (TADDOL's 2a-e and NOBIN's 3a-h) can be used as chiral catalysts in the enantioselective alkylation, as exemplified by the reaction of Schiff's bases 1a-e derived from alanine esters and benzaldehydes with active alkyl halides. Acid-catalyzed hydrolysis of the products formed in the reaction afforded (R)-alpha-methylphenylalanine, (R)-alpha-naphthylmethylalanine, and (R)-alpha-allylalanine in 61-93% yields and with ee 69-93%. The procedure could be successfully scaled up to 6 g of substrate 1b. When (S,S)-TADDOL or (R)-NOBIN are used, the (S)-amino acids are formed. A mechanism rationalizing the observed features of the reaction has been suggested.     

New alkyl-cobalt(III) complexes containing chiral centers in the chelating system

The complex mer-[Co(III)(L(1)Npy)(2)](+) (1') where the L(1)Npy(-) is the tridentate 3-[(2-pyridyl)methylimino]butan-2-one oximate ligand, gives alkyl-cobalt derivatives after reduction with NaBH(4)/Pd(2+) to the Co(I) and alkylation. The formation of the cobalt-carbon bond is accompanied by the reduction to the amino form of one or both imino ligands (depending on the experimental conditions) initially present in 1'. In one series of experiments, complexes of the type fac-[RCo(III)(L(1)Npy)(H-L(1)NHpy)](+) (R = Me, i-Pr, CH(2)Cl, CH(2)Br, CH(2)CF(3), and Bz) were obtained, in which only one of the two ligands was reduced to the amino form (H-L(1)NHpy). The saturation of one azomethine group causes the products to assume a fac configuration and induces the formation of one asymmetric carbon and one asymmetric nitrogen center in the chelating system. When an excess of reducing agent is used, both azomethine groups may be saturated, causing the introduction of one pair of chiral carbons and one pair of chiral nitrogens. Two isomers of the methyl derivative [MeCo(III)(L(1)NHpy)(H-L(1)NHpy)](+) were isolated. The X-ray analysis reveals that these isomers differ from one another in configuration of the C and N chiral centers. Possible reaction mechanisms leading to these different types of complexes are proposed.     

(Salen)Ti(IV)-Catalyzed Asymmetric Ring-opening of meso Epoxides Using Dithiophosphorus Acid as the Nucleophile

As an important strategy for the formation of 1,2-bifunctionalized systems theasymmetric ring-opening of epoxides with different nucleophiles has drawn muchattention from the organic chemists. A wide variety of nucleophiles are utilized in theaforemention…     

Catalytic asymmetric Mannich reactions of glycine derivatives with imines. A new approach to optically active alpha,beta-diamino acid derivatives

Imines of glycine alkyl esters react with imines in a diastereo- and highly enantioselective Mannich reaction in the presence of chiral copper(I) complexes as the catalyst to give optically active alpha,beta-diamino acid derivatives. A series of imines of glycine esters derived from glycine and aromatic carbonyl compounds has been screened as substrates for the Mannich reaction with different imines in the presence of various combinations of metal salts and chiral ligands. The benzophenone imine of glycine esters was found to react with N-protected imines in a diastereoselective fashion giving functionalized alpha,beta-diamino acid esters with excellent enantioselectivities. The most effective chiral catalysts are chiral copper(I) complexes having phosphino-oxazoline (P,N)-ligands, and among these ligands, those derived from (1R,2S)-dihydroxy-1,2,3,4-tetrahydronaphthalene gave the best results. The scope of this new catalytic asymmetric reaction of the benzophenone imine glycine esters is demonstrated for the reaction with different N-protected-C-aryl and C-alkyl imines giving the Mannich adducts with excellent optical purity. Furthermore, the synthetic aspects of the reaction are presented by converting the Mannich adducts into alpha,beta-diamino acid derivatives. The relative and absolute configuration of the Mannich adduct have been determined and based on the stereochemical outcome of the reaction a tetrahedral chiral-copper(I)-imino glycine alkyl ester intermediate is proposed. In this intermediate the Re-face of the benzophenone imine glycine ester is shielded by the chiral ligand leaving the Si-face available for approach of the Si-face of the imine. A series of semiempirical calculations has been performed to support the structure of the tetrahedral chiral-copper(I) complex and to account for the influence of the substituents in the chiral phosphino-oxazoline ligands.