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.     

Enantioselective synthesis of (2R,3R)- and (2S,3S)-2- [(3-chlorophenyl)-(2-methoxyphenoxy)methyl]morpholine

The enantioselective synthesis of the (R,R)- and (S,S)-enantiomers of 1 from commercially available 3-chlorocinnamic acid is reported. The Sharpless asymmetric epoxidation was used to establish the stereocenters in the synthesis of both enantiomers of 1.     

Diastereoselective synthesis of (R*,R*)-ethyl 2-[1H-indol-3-yl(phenyl)methyl]-3-oxobutanoate

Russian Chemical Bulletin -     

3-(((1S,3S)-3-((R)-Hydroxy(4-(trifluoromethyl)phenyl)methyl)-4-oxocyclohexyl)methyl)pentane-2,4-dione: Design and Synthesis of New Stereopure Multi-Target Antidiabetic Agent

The chiral drug candidates have more effective binding affinities for their specific protein or receptor site for the onset of pharmacological action. Achieving all carbon stereopure compounds is not trivial in chemical synthesis. However, with the development of asymmetric organocatalysis, the synthesis of certain vital chiral drug candidates is now possible. In this research, we have synthesized 3-(((1S,3S)-3-((R)-hydroxy(4-(trifluoromethyl)phenyl)methyl)-4-oxocyclohexyl)methyl)pentane-2,4-dione (S,S,R-5) and have evaluated it potential as multi-target antidiabetic agent. The stereopure compound S,S,R-5 was synthesized with a 99:1 enantiomeric ratio. The synthesized compound gave encouraging results against all in vitro antidiabetic targets, exhibiting IC₅₀ values of 6.28, 4.58, 0.91, and 2.36 in α-glucosidase, α-amylase, PTP1B, and DPPH targets, respectively. The molecular docking shows the binding of the compound in homology models of the respective enzymes. In conclusion, we have synthesized a new chiral molecule (S,S,R-5). The compound proved to be a potential inhibitor of the tested antidiabetic targets. With the observed results and molecular docking, it is evident that S,S,R-5 is a potential multitarget antidiabetic agent. Our study laid the baseline for the animal-based studies of this compound in antidiabetic confirmation.     

Synthesis and Crystal Structure of tert-Butyl(((2R,3R,6R)-3-hydroxy-6-(nitromethyl)-3,6-dihydro-2H-pyran-2-yl)methyl)carbonate

In this paper, a β-C-pyranogalactoside(Ⅸ) was synthesized from D-galactose through a nine-step reaction with a total yield of 32% under the palladium catalyst, and its structure was characterized by nuclear magnetic resonance(NMR) and high-resolution electrospray ionization mass spectrometry(HR-ESI-MS). The absolute configuration of this pyranogalactoside was confirmed with a Flack parameter of –0.01(6) by X-ray crystallography using a Cu radiation source. Compound(Ⅸ), C_(12) H_(19) NO_7, crystal data: monoclinic system, space group P2_12_12_1, a = 8.53480(10), b = 9.4207(2), c = 18.1308(3) ?, V = 1457.79(4) ?~3, Z = 4, F(000) = 616, Dc =1.318 g/cm3, μ = 0.931 mm~(-1), R = 0.0294 and w R = 0.0752 for 2875 independent reflections(R_(int) = 0.0163) and 2857 observed ones(I 2σ(I)).     

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.     

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.     

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…     

Crystal and molecular structure of methyl(±)-2-((1R,3R)-3-{ 2-[(3S)-1-ethyl-3-hydroxy-2-oxo-2,3-dihydro-1H-3-indolyl]acetyl}-2,2-dimethylcyclobutyl) acetate

The structure of methyl (±)-2-((1R,3R)-3-{ 2-[(3S)-1-ethyl-3-hydroxy-2-oxo-2,3-dihydro-1H-3-indolyl]acetyl}-2,2-dimethylcyclobutyl) acetate has been determined by single crystal X-ray diffraction. The crystal belongs to triclinic system; parameters of the unit cell are: a = 6.551(1) Å, b = 11.506(1) Å, c = 14.334(1) Å, α = 101.41(1)°, β = 97.57(1)°, γ = 104.72(1)°; space group P-1, Z = 2, composition C₂₁H₂₇NO₅. The structure of N-ethyloxindole fragment is usual for the present class of compounds. The configuration of the formed asymmetric carbon atom C(3) of the pyrrole ring along with the configuration of C(12) and C(14) atoms of 2,2-dimethylcyclobutane ring form the side chain of the molecule were determined. There is observed the generation of centrosymmetrical dimers in the crystal structure due to realized intermolecular hydrogen bond of O-H...O type, 2.808(2) Å.     

Production of (2R,3S)-3-(4-methoxyphenyl)glycidic acid methyl ester using an emulsion bioreactor containing lipase fromSerratia marcescens

An emulsion bioreactor for production of (2R,3S)-3-(4-methoxyphenyl) glycidic acid methyl ester ([-]MPGM) from a racemic mixture ([±]MPGM) using the lipase fromSerratia marcescens has been proposed. Kinetics of hydrolyzing reaction and purification of (-)MPGM from the reaction mixture were investigated to provide a basis for industrial application of this bioreactor. The hydrolyzing reaction in the bioreactor proceeded at a rate that was first order in substrate concentration. The reaction rate was affected by a stirring speed and the ratio of the aqueous phase containing lipase to the toluene phase containing substrate. Phase separation after the enzymatic reaction was accomplished by addition of surfactant to the reaction mixture, and crystalline (-)MPGM with a chemical purity of 100% and optical purity of 100% enantiomeric excess was obtained in a high yield of 40–43% by concentration of the toluene solution.     

Synthesis and Absolute Configuration of((2R,3R,6S)-3-Hydroxy-6-(naphthalen-2-ylthio)-3,6-dihydro-2H-pyran-2-yl)methyl Pivalate

A stereo-selective palladium-catalyzed one-pot Tsuji-Trost reaction was used to prepare four β-thiogalactosides from unsaturated D-galactal and thiol. Their structures were characterized by nuclear magnetic resonance spectra and high-resolution electrospray ionization mass spectra. The absolute configuration was confirmed with a Flack parameter of 0.019(15) by X-ray crystallography using a Cu radiation source. Compound 6 a(C_(21) H_(24) O_4 S): orthorhombic system, space group P2_12_12_1, a = 9.0919(4), b = 9.6313(4), c = 22.5936(11) ?, V =1978.45(15) ?~3, Z = 4, F(000) = 792, Dc = 1.250 g/cm~3, μ = 1.636 mm~(-1), R = 0.0478 and w R = 0.1384 for 3621 independent reflections(Rint = 0.0390) and 3326 observed ones(I 2σ(I)). 3-(4,5)-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide(MTT) cell viability assays indicated that these thiogalactosides showed anti-proliferative activities against human gastric cancer HGC-27 cells with IC50 values of 69～88 μM.