A Computational Study of Conformers of 2-Thiaoxacyclohexane (1,2-Oxathiane)

Ab initio molecular orbital theory with the 6-31G(d), 6-31G(2d), 6-31+G(d), 6-31G(d,p), 6-31+G(d,p), and 6-311G(d,p) basis sets and the hybrid density functionals B3LYP, B3P86, and B3PW91 have been used to calculate the optimized geometries and relative energies of the chair, half-chair, sofa, twist, and boat structures of 2-thiaoxacyclohexane (1,2-oxathiane). The values of the energy difference (E, kcal/mol) between the chair and 3,6-twist structures of 1,2-oxathiane were 4.92 (HF), 4.73 (MP2), and 4.66 (DFT). The HF chair–twist energy difference (G _c–t ^o) for 1,2-oxathane was 5.16 kcal/mol. Intrinsic reaction coordinate (IRC) calculations connected a transition state (TS-A) between the chair conformation and the less stable 2,5-twist form and connected two transition states (TS-B, TS-C) between the chair conformation and the more stable 3,6-twist conformer. The DFT energy differences between the chair and TS-A, TS-B, and TS-C were 11.4, 10.8, and 12.6 kcal/mol, respectively. Hyperconjugative stereoelectronic interactions were observed in the chair (n _o and ) and 3,6-twist (n _S and n _O ) conformers of 1,2-oxathiane. The chair conformation of 1,2-oxthiane is 9.6 and 10.0 kcal/mol, respectively, less stable than the chair conformations of 3-thiaoxacyclohexane (1,3-oxathiane) and 4-thiaoxacyclohexane (1,4-oxathiane, thioxane).     

神经氨酸酶与3-(3-戊氧基)安息香酸作用机制的理论研究

运用柔性分子对接和分子动力学方法, 深入研究了4-(氮乙酰氨基)-5-胍基-3-(3-戊氧基)安息香酸(BA)与各类型神经氨酸酶(N1, N2, N9亚型和B型)间的作用机制. 结果显示, BA与各类型神经氨酸酶结合模式存在差异, 但作用机制比较相似: 与它们的活性腔均匹配良好, 并形成稳定的复合体系, 最大结合能分别等于－1233.62, －1385.72, －663.11, －1058.87 kJ•mol^－1. 这表明BA对各类型神经氨酸酶均有良好的抑制效果. 进一步分析发现, BA与各类型神经氨酸酶活性腔内保守关键氨基酸残基发生较强的静电和氢键作用, 而与易突变氨基酸残基作用较弱, 表明了活性腔内易突变氨基酸残基发生突变也不会对抑制效果造成明显影响. 因此, BA是一种极具应用前景的新型抗流感病毒药物. 结合以前的研究结果, 我们提出了以BA为底物的抗流感病毒药物的修饰方向.     

A Convenient Preparation of (R)-7-(3-Benzothienylglycylamido)deacetoxycephalosopranic Acid

An efficient synthesis of (R)-7-(3-benzothienylamido)deacetoxy-cephalosporanic acid (1) is described beginning from (R)-alpha-aminobenzo[b]thiophene-3- acetic acid (2) and 7-amino-3-methyl-3-cephem-4-carboxylic acid (7-ADCA). Good yields were obtained and the procedure is amenable to multikilogram preparations.     

Modified synthesis of methyl (1R,2R,3E,5R)-3-(hydroxyimino)-5-methyl-2-(1-methylethyl)-cyclohexanecarboxylate from (R)-4-menthen-3-one

A modified stereospecific synthesis of potentially biologically and pharmacologically active methyl (1R,2R,3E,5R)-3-(hydroxyimino)-5-methyl-2-(1-methylethyl)cyclohexanecarboxylate from (R)-4-menthen-3-one was developed using sequential 1,4-conjugate addition of Norman reagent catalyzed by CuI?CBF₃?Et₂O?CCuCl₂ and ozonolysis?Creduction of the intermediate (R,R,R)-vinylmenthone by hydroxylamine hydrochloridein MeOH.     

Quantum Computational Investigation of (E)-1-(4-methoxyphenyl)-5-methyl-N′-(3-phenoxybenzylidene)-1H-1,2,3-triazole-4-carbohydrazide

The title compound was synthesized and structurally characterized. Theoretical IR, NMR (with the GIAO technique), UV, and nonlinear optical properties (NLO) in four different solvents were calculated for the compound. The calculated HOMO–LUMO energies using time-dependent (TD) DFT revealed that charge transfer occurs within the molecule, and probable transitions in the four solvents were identified. The in silico absorption, distribution, metabolism, and excretion (ADME) analysis was performed in order to determine some physicochemical, lipophilicity, water solubility, pharmacokinetics, drug-likeness, and medicinal properties of the molecule. Finally, molecular docking calculation was performed, and the results were evaluated in detail.     

The Synthesis of 3-(R)- and 3-(S)-Hydroxyeicosapentaenoic Acid

Monohydroxylated polyunsaturated fatty acids belonging to the oxylipin class of natural products are present in marine and terrestrial sources as well as in the human body. Due to their biological activities and role in diverse biosynthetic pathways, oxylipins biosynthesized from eicosapentaenoic acid and arachidonic acid have attracted great interest from the scientific community. One example is 3-hydroxyeicosapentaenoic acid where the absolute configuration at C-3 has only been tentatively assigned. In this paper, studies on acetate type aldol reactions that enabled the preparation of 3-(R)-hydroxyeicosapentaenoic acid (3R-HETE, 2) and its enantiomer are presented.     

Die stereospezifische Reduktion von (1R)-3-endo-Aminocampher zu (1R)-3-endo-Aminoborneol

The highly stereospecific reduction of (1R)-3-endo-aminobornan-2-one ( 2 ) to [1R]-3-endo-amino-2-endom-bornanol ( 1 ) is described. This reaction is achieved by using alkylaluminumdichlorides, a new group of reducing agents for the reduction of the ketone 2 to the secondary alcohol 1

1 Diesc Reduktion ist Gegenstand van Patcntanmeldungen, z. B. [l].

     

Stereoselective synthesis of (S)-3-(methylamino)-3-((R)-pyrrolidin-3-yl)propanenitrile

(S)-3-(methylamino)-3-((R)-pyrrolidin-3-yl)propanenitrile (1) is a key intermediate in the preparation of PF-00951966, (1) a fluoroquinolone antibiotic for use against key pathogens causing community-acquired respiratory tract infections including multidrug resistant (MDR) organisms. The current work describes the development of a highly efficient and stereoselective synthesis of 1 in 10 steps with an overall yield of 24% from readily available benzyloxyacetyl chloride. Two key transformations in the synthetic sequence involve (a) catalytic asymmetric hydrogenation with chiral DM-SEGPHOS-Ru(II) complex to afford β-hydroxy amide 11b in good yield (73%) and high stereoselectivity (de 98%, ee >99%) after recrystallization and (b) S(N)2 substitution reaction with methylamine to provide diamine 14 with inversion of configuration at the 1'-position in high yield (80%), after efficient purification using a simple acid/base extraction protocol.     

A scalable synthesis of (R)-3-(2-aminopropyl)-7-benzyloxyindole via resolution

(±)-3-(2-Aminopropyl)-7-benzyloxyindole 1, assembled from 7-benzyloxyindole 3 in 59% overall yield, is resolved with O,O′-di-p-toluoyl l-(2R,3R)-tartaric acid 7 into (R)-1, a key intermediate of AJ-9677 2 (selective adrenaline β₃-agonist) in 99.5% e.e. and 36% overall yield. The unwanted enantiomer (S)-1 (61.9% e.e.; recovered in 57% yield from the crystallization filtrate) can be reused in another round of resolution after its enantiomeric purity is lowered to 3.7% by Raney Co treatment under a hydrogen atmosphere.     

A Convenient Stereoselective Synthesis of (1R,2S,3R,4S)-3-(Neopentyloxy)isoborneol

A convenient preparation of (1R,2S,3R,4S)-3-(neopentyloxy)isoborneol (= (1R,2S,3R,4S)-3-(2,2-dimethyl-propoxy)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol; 1a ), a valuable chiral auxiliary, is described. The synthesis involves six steps starting from the readily available camphorquinone ( 5 ) and gives 1a in 48% overall yield. The key step is the chemoselective hydrolysis of the less hindered 1,3-dioxolane moiety in the camphorquinone di-acetal 4 .     

Asymmetric Synthesis of (-)-(2R,3R,6S)-Irnigaine

Introduction　　Asarelativelynewmemberofnaturalalkaloidswith2 ,6 disubstituted 3 piperidinolskeleton ,irnigaine 1wasisolatedfromthetubersofArisarumVulgare (Araceae)in1995byMelhaouiandBode .1Itsstructureandrelativeconfigurationswereelucidatedby1HNMRstudiesandtheabsoluteconfigurationwasproposedonthebasisofitsopti calrotation .1Soonafterthen ,Meyerandhisco workersreportedthefirstsynthesisof (- ) (2R ,3R ,6S) irni gaineandtheconfigurationconfirmation .Althoughtheirsynthesisroutewasshortan…     

Chiroptical properties of (R)-3-chloro-1-butene and (R)-2-chlorobutane

Coupled cluster and density functional models of specific rotation and vacuum UV (VUV) absorption and circular dichroism spectra are reported for the conformationally flexible molecules (R)-3-chloro-1-butene and (R)-2-chlorobutane. Coupled cluster length- and modified-velocity-gauge representations of the Rosenfeld optical activity tensor yield significantly different specific rotations for (R)-3-chloro-1-butene, with the latter providing much closer comparison (within 3%) to the available gas-phase experimental data at 355 and 633 nm. Density functional theory overestimates the experimental rotations for (R)-3-chloro-1-butene by approximately 80%. For (R)-2-chlorobutane, on the other hand, all three models give reasonable comparison to experiment. The theoretical specific rotations of the individual conformers of (R)-3-chloro-1-butene are much larger than those of (R)-2-chlorobutane, in disagreement with previous studies of the temperature dependence of the experimental rotations in solution. Simulations of VUV absorption and circular dichroism spectra reveal large differences between the coupled cluster and density functional excitation energies and the rotational strengths. However, while these differences lead to very different specific rotations for (R)-3-chloro-1-butene, they have much less impact on the computed specific rotations for (R)-2-chlorobutane. In addition, the coupled cluster VUV absorption spectrum of (R)-2-chlorobutane compares well to experiment.     

Practical and stereocontrolled syntheses of both (1R,3S)- and (1R,3R)-3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethylcyclopropanecarboxylates

The title compounds of (1R*,3S*) configuration were prepared from 3-formyl-2,2-dimethyl-cyclopropanecarboxylate by addition of CF₃CCl₂ZnCl, acetylation, and reductive β-elimination with zinc, whereas the (1R*,3R*) isomer was derived from Me₂C=CHCH(OH)CCl₂CF₃ by diazoacetylatlon. Cu(II) catalyzed intramolecular cyclization, and the zinc reduction.     

Studies on the transformation of nitrosugars into iminosugars III: synthesis of (2R,3R,4R,5R,6R)-2-(hydroxymethyl)azepane-3,4,5,6-tetraol and (2R,3R,4R,5R,6S)-2-(hydroxymethyl)azepane-3,4,5,6-tetraol

A divergent synthesis of the two novel polyhydroxylated azepanes (2R,3R,4R,5R,6R)-2-(hydroxymethyl)azepane-3,4,5,6-tetraol and (2R,3R,4R,5R,6S)-2-(hydroxymethyl)azepane-3,4,5,6-tetraol from d-mannose is described. The method involves a Henry reaction between dimethyl-tert-butylsilyl 2,3-O-isopropylidene-α-d-lyxo-pentodialdo-1,4-furanoside and 2-nitroethanol followed by a reductive ring closure of the resulting epimeric nitro aldols. Glycosidase inhibition tests showed that (2R,3R,4R,5R,6S)-2-(hydroxymethyl)azepane-3,4,5,6-tetraol exhibits a weak but selective inhibition against α-l-fucosides.     

合成(3R,4R)-3-[(1'R)-叔丁基二甲基硅氧乙基]-4-乙酰氧基-2-氮杂环丁酮的新方法

(3R,4R)-3-[(1'R)-叔丁基二甲基硅氧乙基]-4'-乙酰氧基-1-对甲氧基苯基-2-氮杂环丁酮依次经铋酸钠/浓硫酸体系氧化和亚硫酸氢钠还原,合成了培南类药物的重要中间体——(3R,4R)-3-[(1'R)-叔丁基二甲基硅氧乙基]-4-乙酰氧基-2-氮杂环丁酮(1),收率62%,纯度98%,其结构经1H NMR,IR和EI-MS表征。