An Efficient Synthesis of Optically Pure (R)- and (S)-2-(aminomethyl)alanine ((R)- and (S)-ama) and (R)- and (S)-2-(aminomethyl)leucine ((R)- and (S)-aml)

An efficient synthesis of enantiomerically pure (R)- and (S)-2-(aminomethyl)alanine ((R)- and (S)-Ama) 1a and (R)- and (S)-2-(aminomethyl)leucine ((R)- and (S)-Aml) 1b is described (Schemes 1 and 2). Resolution of the racemic amino acids was achieved using L -phenylalanine cyclohexylamide ( 2 ) as chiral auxiliary. The free amino acids 1a, b were converted to the N^α-Boc,N^γ-Z-protected derivatives 11a, b (Scheme 3) ready for incorporation into peptides. Based on the three crystal structures of the diastereoisomeric peptides 8a, 8b , and 9b , the absolute configurations in both series were determined. β-Turn type-I geometries were observed for structures 8b and 9b , whereas 8a crystallized in an extended backbone conformation.     

(+)-(5R,6S)-2-(1′-Aminoalkyl)-6-(hydroxyalkyl)penem-3-carboxylic Acids

In continuation of our work on penem antibiotics, novel chiral (5R,6S)-2-(1′-aminoalkyl)-6-(hydroxyalkyl)-derivatives 1 have been synthesized by two essentially different strategies. Whereas the starting materials for 1a - f , azetidinones 2 and 5 , were obtained from chiral building blocks (6-aminopenicillanic acid and L-threonine, resp.), the one for 1g , azetidinone 9 , was derived from racemic 4-acetoxyazetidinone and, as chiral auxiliary, (2R)-2-mercaptopropan-1-ol. The 2-aminomethyl derivatives 1a (CGP 30 779) and 1f (CGP 31 608) proved the most potent compounds in the antibacterial tests in vitro and showed a well-balanced spectrum of activity by comparison with that of established β-lactams.     

Structural and temperature effects in the high-performance liquid chromatographic enantioseparation of 1-(alpha-aminobenzyl)-2-naphthol and 2-(alpha-aminobenzyl)-1-naphthol analogs

The enantiomers of 1-(alpha-aminobenzyl)-2-naphthol and 2-(alpha-aminobenzyl)-1-naphthol analogs were separated isothermally on a cellulose-tris-3,5-dimethylphenyl carbamate-based chiral stationary phase (Chiralcel OD-H), at 10 degrees C increments in the range of 5-35 degrees C, using n-hexane/2-propanol/diethylamine as mobile phase. The mobile phase composition and temperature were varied to achieve baseline resolutions in a single chromatographic run. The dependence of the natural logarithms of selectivity factors, In alpha, on the inverse of temperature, 1/T, was used to determine the thermodynamic data of the enantiomers. The thermodynamic data revealed that all the compounds in this study separate via the same enthalpy-driven chiral recognition mechanism.     

Thin layer chromatographic resolution of some 2-arylpropionic acid enantiomers using L-(-)-serine,L-(-)-threonine and a mixture of L-(-)-serine and L-(-)-threonine-impregnated silica gel as stationary phases

Impregnated silica TLC plates with L-(-)-serine and L-(-)-threonine and a mixture of L-(-)-serine and L-(-)-threonine (1:1) as chiral selectors were prepared to use as chiral stationary phases (CSPs) in thin layer chromatography. The resolution of the enantiomers of 2-arylpropionic drugs, including ibuprofen, ibuproxam, ketoprofen, pranoprofen, benoxaprofen, flurbiprofen and tiaprofenic acid was investigated on these CSPs. A mobile phase system of acetonitrile-methanol-water (16:4:0.5, v/v/v) was used. The spots were detected with iodine vapours and the detection limits were found to range between 0.25 and 0.5 micro g/mL for all racemic compounds investigated. The effect of temperature, pH and concentration of the impregnating chiral selectors on resolution has been studied.     

New liquid crystal compounds ( )-4-[5-(2-Methylbutyl)-1,3-dioxan-2-yl]phenyl 4-alkoxybenzoate

New liquid crystal compounds, (+)-4-[5-(2-methylbutyl)-1,3-dioxan-2-yl] phenyl 4-alkoxybenzoates (5), were synthesized. The mesomorphic behaviour of these compounds is compared with that of (+)-4-(5-alkyl-1,3-dioxan-2-yl)-phenyl 4-(2-methylbutoxy)benzoates (6). While compounds 6 exhibited a chiral smectic C phase, the corresponding compounds 5 did not. This might mean that for the appearance of a chiral smectic C phase in these types of compounds, it is necessary that the carbonyl and the chiral groups exist at nearby positions. Transition temperatures to those isotropic state for compounds 5 were lower than those for compounds 6. This result is common in both cases of (+)-4-alkoxycarbonylphenyl-4-[5-(2-methylbutyl)-1,3-dioxan-2-yl]benzoates (7), and (+)-4-(2-methylbutoxy-carbonyl)phenyl 4-(5-alkyl-1,3-dioxan-2-yl)-benzoates (8).     

Development of versatile cis- and trans-dicarbon-substituted chiral cyclopropane units: synthesis of (1S,2R)- and (1R,2R)-2-aminomethyl-1-(1H-imidazol-4-yl)cyclopropanes and their enantiomers as conformationally restricted analogues of histamine

The cyclopropane ring can be used effectively in restricting the conformation of biologically active compounds to improve activity and also to investigate bioactive conformations. We designed (1S,2R)- and (1R,2R)-2-aminomethyl-1-(1H-imidazol-4-yl)cyclopropanes (1 and 2, respectively) and their enantiomers (ent-1 and ent-2) as conformationally restricted analogues of histamine. The four types of chiral cyclopropanes bearing two differentially functionalized carbon substituents in a cis or trans relationship on a cyclopropane ring, (1S,2R)-2-(tert-butyldiphenylsilyloxy)methyl-1-formylcyclopropane (7) and (1R,2R)-2-(tert-butyldiphenylsilyloxy)methyl-1-formylcyclopropane (8) and their enantiomers (ent-7 and ent-8), were developed as the key intermediates for synthesizing 1, 2, ent-1, and ent-2. The reaction between (R)-epichlorohydrin [(R)-12] and phenylsulfonylacetonitrile (13a) in the presence of NaOEt in EtOH followed by treatment with acid gave the chiral cyclopropane lactone 11a with 98% ee in 82% yield. Compound 11a was converted into both the cis- and trans-chiral cyclopropane units 7 and 8, respectively, via reductive desulfonylation with Mg/MeOH as the key step. The corresponding enantiomers, the cis-substituted ent-7 and the trans-substituted ent-8, were also prepared starting from (S)-epichlorohydrin [(S)-12]. The four conformationally restricted target histamine analogues 1, 2, ent-1, and ent-2 were successfully synthesized from 7, 8, ent-7, and ent-8, respectively. The chiral cyclopropane units 7, 8, ent-7, and ent-8 should be useful as versatile intermediates for synthesizing various compounds having an asymmetric cyclopropane structure.     

Racemic and asymmetric Diels-Alder reactions of 1-(2-oxazolidinon-3-yl)-3-siloxy-1,3-butadienes

Achiral and chiral 1-(2-oxazolidinon-3-yl)-3-siloxy-1,3-butadienes were prepared from readily available starting materials. Although more stable than the parent 1-amino-3-siloxy dienes, the 1-(2-oxazolidinon-3-yl)-3-siloxy-1,3-butadienes are still very reactive in Diels-Alder reactions, somewhat more than 1,3-dialkoxy-1, 3-butadienes (e.g., Danishefsky's diene). The cycloadditions of the achiral and chiral dienes with several different dienophiles were examined. The reactions proceeded in good yield, with modest to high endo selectivity. The chiral dienes exhibited excellent facial selectivity in cycloadditions with alpha-substituted acroleins, maleic anhydride and N-phenylmaleimide. Upon reduction and hydrolysis of the cycloadducts, substituted cyclohexenones were obtained with ee's ranging from 22% to >98%.     

N-(S)-(1’-氯甲基-2’-烷基)-2-乙基-2-(4S-烷基-4,5-二氢噁唑)丁酰胺的合成

由L-氨基酸不对称合成了4种新型手性化合物(6a,6b,7a,7b),其结构经IR,~1H NMR,~(13)C NMR及MS等证实。     

5-羟基色胺受体激动剂(1R,2S)-(-)-2-(2-羟基苯基)-N,N-二丙基环丙胺的不对称合成

利用手性双唑啉与三氟甲磺酸亚铜催化2-甲氧基苯乙烯与重氮乙酸二环己基甲酯的不对称环丙烷化反应合成了手性环丙烷羧酸酯,用氢氧化钠对其进行选择性水解得到全反式环丙烷羧酸,其ee值经GC测定为88%.进一步经过Curtius重排、烷基化等反应及重结晶等步骤合成了光学纯的具有生理活性的环丙胺化合物1a和1b.     

Synthesis and ferroelectric properties of chiral swallow-tailed liquid crystals derived from (S)-2-[1-(2-ethylbutoxy)]propanol

(S)-2-[1-(2-Ethylbutoxy)]propanol was designed and synthesized as a chiral building block for the preparation of chiral liquid crystals. Its derivatives, the (S)-2-[1-(2-ethylbutoxy)]propyl 4-[4-(4-alkoxyphenyl)phenoyloxy]benzoates, EPmPPB (m = 8-12), were prepared and their mesomorphic phases investigated. The results showed that the chiral materials displayed enantiotropic SmA* and SmC* phases, while those with shorter alkyl chains (m = 8-10) displayed an additional unidentified SmX* phase. The switching current, spontaneous polarization, tilt angle, dielectric constant and electro-optical response for the materials in the ferroelectric SmC* phase were measured. The electro-optic responses of the materials in polyimide film-coated, homogeneously aligned cell exhibit thresholdless, V-shaped switching in the ferroelectric phase.     

Simple chiral urea gelators, (R)- and (S)-2-heptylurea: their gelling ability enhanced by chirality

We present the first report on the synthesis of chiral ureas, (R)- and (S)-2-heptylurea, and their gelling behaviors. The ureas were prepared by the reactions of chiral amines and phenyl carbamate in the presence of triethylamine. On cooling from homogeneous solutions, the chiral ureas form gels in water and various nonpolar organic solvents, such as cyclohexane, toluene, and tetrachloromethane, while the racemate gelatinize only toluene and tetrachloromethane among the solvents we examined. The gelling ability of the enantiomeric urea is higher than the racemate, as the critical gelling concentrations in toluene, for example, were 0.2% and 0.7% (wt/wt), respectively. The enhanced gelling ability of the enantiomeric ureas is due to the 1D supramolecular structure formed during gelation. In contrast, the racemate crystallizes into two-dimensional lamellae, where the (R)- and (S)-2-heptylurea exist alternatingly in a plane (P2(1)/c space group). Powder X-ray diffraction pattern of the enantiomeric urea showed that it has a different crystal lattice from that of the racemate, implying that the steric effect by the methyl group at the chiral center prevents the pure enantiomers from having 2D hydrogen bonding networks, which lead to sheet-like structures for the racemate and the achiral analog. Thus the pure enantiomers self-organize into one-dimensional fibrous structures. The simplicity and the ambidextrous gelling behaviors of the chiral ureas in forming both hydrogels and organogels present numerous possibilities for future applications.     

Novel second-harmonic-generation-active lead(II) phosphinate based on 2-carboxyethyl(phenyl)phosphinate ligand

The hydrothermal reaction of PbCl(2) with the achiral 2-carboxyethyl(phenyl)phosphinate ligand (H(2)L) afforded a novel lead(II) phosphinate that contains two enantiomers as a racemic mixture, namely, [Pb(HL)(2)] (Λ- and Δ-1). Each enantiomer features a two-fold symmetrical chiral chain, in which the adjacent Pb(2+) ions are doubly bridged by pairs of HL(-) ligands. The uni-oriented stacking of such 1D chains by edge-to-face π···π interactions results in its crystallization in the chiral C2 space group. Complex 1 shows a second harmonic generation response that is ～2 times that of KDP (KH(2)PO(4)).     

(2S)-(+)-2-溴-1-(6'-甲氧基-2'-萘基)丙-1-酮的不对称合成

以(2R,3R)-酒石酸二甲酯为手性辅助剂,6-甲氧基-2-丙酰基萘经缩酮化、溴化铜不对称溴化、水解等反应合成了(2S)-2-溴-1-(6'-甲氧基-2'-萘基)丙-1-酮。总收率94%。     

N-杂环甲基2-(4-杂芳氧基苯氧基)丙酰胺的合成及除草活性

以2-(4-羟基苯氧)丙酸为原料,设计合成了16个新的手性N-杂环甲基2-(4-杂芳氧基苯氧基)丙酰胺化合物,其化学结构经核磁共振、色谱-质谱、红外光谱及元素分析确证.初步生物活性测定结果表明,合成的化合物在2.25×103g/ha剂量时对单子叶杂草马唐(Digitaria sanguinalis)、稗草(Echinochloa crus-galli)及狗尾草(Setaria viridis)等均具有90%以上的活性;进一步活性及作物安全性测试表明,化合物(R)-(+)-N-[(6-氯吡啶-3-基)甲基]-2-[4-(3-氯-5-三氟甲基吡啶-2-基氧基)苯氧基]丙酰胺(2b)的除草活性高于噁唑酰草胺,且对水稻茎叶处理安全,同时对水稻田主要杂草千金子的活性远高于氰氟草酯;化合物的除草活性与立体构型有关,R构型为活性构型.     

High-performance liquid chromatographic enantioseparation of 1-(phenylethylamino)- or 1-(naphthylethylamino)methyl-2-naphthol analogs and a temperature-induced inversion of the elution sequence on polysaccharide-based chiral stationary phases

The stereoisomers of five 1-(phenylethylamino)methyl-2-naphthol analogs or 1-(naphthylethylamino)methyl-2-naphthol analogs containing two chiral centers were directly separated on chiral stationary phases containing the chiral selectors cellulose tris-(3,5-dimethylphenyl) carbamate (Lux Cellulose-1), cellulose tris-(3-chloro-4-methylphenyl) carbamate (Lux Cellulose-2) and amylose tris-(5-chloro-2-methylphenyl) carbamate (Lux Amylose-2). Experiments were performed in normal-phase mode in a wide temperature range -5 to 70°C. Thermodynamic parameters and T(iso) values were calculated from plots of lnk or lnα vs. 1/T. -Δ(ΔH°) ranged from 1.0 to 4.7 kJ mol(-1), -Δ(ΔS°) from 1.6 to 11.0 J mol(-1) K(-1) and -Δ(ΔG°) from 0.1 to 1.5 kJ mol(-1). The sequence of elution of the stereoisomers was determined in all cases and in one case a temperature-induced inversion of the elution sequence was observed.     

Synthesis of chiral 2-(anilinophenylmethyl)pyrrolidines and 2-(anilinodiphenylmethyl)pyrrolidine and their application to enantioselective borane reduction of prochiral ketones as chiral catalysts

Chiral diamines, 2-(anilinophenylmethyl)pyrrolidines and 2-(anilinodiphenylmethyl)pyrrolidine, were prepared from N-(tert-butoxycarbonyl)pyrrolidine or (S)-proline as a starting material, respectively. These chiral diamines were efficient for the catalytic enantioselective borane reduction of acetophenone. Using (S)-2-(anilinodiphenylmethyl)pyrrolidine, chiral secondary alcohols were obtained from prochiral ketones with good to excellent enantiomeric excesses (up to 98% ee).     

(S)-(—)-2-(苯胺甲基)吡咯烷的高分子化及在不对称还原中的应用

<正> 近十多年来,不对称反应方面的研究工作十分活泼,由于手性试剂和催化剂的发展,使许多不对称反应的旋光收率可高达90％以上。以手性膦为配位体的铑(Ⅰ)络合物对脱氢氨基酸衍生物的不对称氢化反应已经工业化,而更多的不对称反应正被广泛地用于天然产物的合成中。     

5-(对-羟基苯基):-5-苯基乙内酰脲的反相高效液相手性分离测定法

以β－ＣＤ为手性流动相添加剂、苯巴比妥为内标,于ＦＬＣ－Ｃ８反相柱上建立了鼠肝微粒体中５－（对－羟基苯基）－５－苯基乙内酰脲（ｐ－ＨＰＰＨ）外消旋体的拆分方法。测得ｐ－ＨＰＰＨ对映体的线性范围为０．５～１１０ｍｇ／Ｌ（ｒ＝０．９９９６）;最低检出量为５ｎｇ（Ｓ／Ｎ＝３）;Ｓ－ｐ－ＨＰＰＨ的回收率为９３．６％±２．８％,Ｒ－ｐ－ＨＰＰＨ的回收率为９４．７％±１．８％;日内和日间精密度ＲＳＤ值均小于２％。所建立的方法具有结果准确、操作方便等特点。     

Asymmetric synthesis of (-)-eburnamonine and (+)-epi-eburnamonine from (4S)-4-ethyl-4-[2-(hydroxycarbonyl)ethyl]-2-butyrolactone.

The key chiral nonracemic 4,4-disubstituted 2-butyrolactone carboxylic acid, (S)-4, is readily accessible via an efficient and stereospecific dirhodium(II) tetraacetate catalyzed tertiary C-H insertion reaction of the diazomalonate (S)-5. The coupling of the acid (S)-4 with tryptamine produces the amide (S)-3, which is then transformed into the aldehyde 23 and hydroxy-lactam 24. Acid-mediated Pictet-Spengler cyclization of 23 and 24 produces the tetracyclic indole lactams (1S,12bS)-25a and (1S,12bR)-25b. Compounds 25a and 25b are converted, via the lactam alcohols 30a and 30b, to (-)-eburnamonine (1a) and (+)-epi-eburnamonine (1b).     

A practical preparation of enantiomerically pure (R)- and (S)-2-bromohexadecanoic acids

The efficient preparation of enantiomerically pure (R)- and (S)-2-bromohexadecanoic acids with e.e.>95% through resolution with the use of a recoverable chiral auxiliary is described. The procedure involves three reactions: Steglich esterification, DIBAL reduction, and Sharpless oxidation. The assessment of the enantiomeric purity is based on NMR analysis by using (1R,2R)-(+)-diphenylethane-1,2-diamine as a chiral solvating agent.