Evaluation of enantioselectivity in lipase-catalyzed acylation of hydroxyalkylphosphine oxides

The lipase-catalyzed optical resolution of 2-, 3-, and 5-hydroxyalkyl phosphorus compounds 1 provided the corresponding optically pure diastereomers in good yields. (S_P, R)- and (R_P, S)-1 were acylated faster than (S_P, S)- and (R_P, R)-1. The stereoselectivity at the phosphorus atom changed with the flexibility of the active sites in the lipases. The stereoselectivity at the phosphorus atom was higher in the reaction of 1a than in the reaction of 1b,c. The reaction rate of ɛ-hydroxyalkylphosphine oxide 1c was faster than that of 1a, although less enantioselectivity was observed at the phosphorus atom.     

Synthesis, characterization of [{(N-methyl-N-benzyl)amino}methyl]ferrocenes and their cyclopalladated complexes: Crystal structure of σ-Pd[(η-C5H5)Fe(η-C5H3CH2N(CH3)CH2C6H4NO2-4)]Cl(PPh3)

Condensation of aminomethylferrocene (1) and substituted benzaldehydes resulted in aldimines 2a-c which followed by reduction with sodium borohydride to give 3a-c. N-methylation of 3a-c with HCHO/NaCNBH₃/HOAc led to 4a-c. Treatment of 4a-c with sodium palladium tetrachloride in the presence of sodium acetate afforded cleanly cyclopalladated 5a-c in which configurations consisted of the R_NR_C, S_NS_C. The preferable activation of C_Ferrocenyl-H bond over C_Phenyl-H bond was also observed. All compounds 2-5 were characterized by elemental analysis, IR and ¹H NMR. In addition, the molecular structure of 5c was confirmed by single crystal X-ray diffraction. The possible mechanism for the formation of 5 was also discussed.     

Uranium complexes of cyclic O,O-bidentate ligands with the P-N-P backbone

The formation of uranium complexes of novel ligands belonging to phosphorylated 2-oxo-1,2-azaphospholane series, namely 2-ethoxy-1-diethoxyphosphoryl-2-oxo-1,2λ⁵-azaphospholane (1a) and both individual R^∗,R^∗- and R^∗,S^∗-diastereomers of the related 2-oxo-2-phenyl-1,2λ⁵-azaphospholanes 1b,c with different surrounding at the exocyclic phosphorus atom, has been studied. The structures of the complexes of ML composition obtained in the reaction with uranyl nitrate in 1:1 ratio were found to depend on the difference in donor properties of the oxygen atom of endo- and exocyclic phosphoryl groups. The ligand 1a possessing the greater difference, serves as O-monodentate one with metal-oxygen bonding via the endocyclic PO function while both isomers of 1b,c coordinate to uranyl cation in a O,O-bidentate fashion. In solutions the ML complexes reacted with air oxygen to afford (μ₂-peroxo)-bridged uranium complexes [{UO₂(L)NO₃}₂(μ₂-O₂)] which structures were confirmed by X-ray crystallography data.     

Organic Solvent-Tolerant Marine Microorganisms as Catalysts for Kinetic Resolution of Cyclic β-Hydroxy Ketones

Chiral cyclic β-hydroxy ketones represent key motifs in the production of natural products of biological interest. Although the molecules are structurally simple, they require cumbersome synthetic steps to get access to them and their synthesis remains a challenge in organic chemistry. In this report, we describe a straightforward approach to enantiomerically enriched (R)- and (S)-3-hydroxycyclopentanone 2a, (R)- and (S)-3-hydroxycyclohexanone 2b, and (R)- and (S)-3-hydroxycycloheptanone 2c involving a transesterification resolution of the racemates using whole cells of marine microorganisms as catalysts and vinyl acetate the acyl donor and solvent. Twenty-six strains from a wide collection of isolates from marine sediments were screened, and seven strains were found to markedly catalyze the resolution in an asymmetric fashion. Using the strain Serratia sp., (R)-2a was isolated in 27% yield with 92% ee and (S)-2a in 65% yield with 43% ee, corresponding to an E-value of 37; (R)-2b was isolated in 25% yield with 91% ee and (S)-2b in 67% yield with 39% ee, corresponding to an E-value of 40; and (R)-2c was isolated in 30% yield with 96% ee and (S)-2c in 63% yield with 63% ee, corresponding to an E-value of 75.     

Dopamine release and molecular modeling study of some coumarin derivatives

4-aryl-2-amino-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)-pyridin-3-carbonitrile (1), 4-aryl-2-oxo-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)-pyridin-3-carbonitriles (2a-2c), 3-(6-aryl-1,2,5,6- tetrahydro-2-thioxopyrimidin-4-yl)-4-hydroxy-2H-chromen-2-one (3a, 3b) and pyrazol-3-yl-4-hydroxycoumarin derivatives (4a-4c, 5, 6a, 6b, 7a, 7b, and 8a-8c) were prepared in order to measure their % change dopamine release in comparison to amphetamine as reference, using PC-12 cells in different concentrations. In addition, the molecular modeling study of the compounds into 3BHH receptor was also demonstrated. The calculated inhibition constant (k_i) implemented in the AutoDock program revealed identical correlation with the experimental results to that obtained binding free energy (ΔG_b) as both parameters revealed reasonable correlation coefficients (R²) being 0.51 involving 10 compounds; (1, 2b, 2c, 3a, 3b, 4a, 4b, 6a, and 8c).     

Aporphine alkaloids and cytotoxic lignans from the roots of Illigera luzonensis

Six aporphine alkaloids, (+)-(S)-N-butyrylcaaverine (1), (+)-(S)-N-propionylcaaverine (2), (+)-(S)-N-acetylcaaverine (3), (+)-(6aR,7R)-N-butyrylnorushinsunine (4), (+)-(6aR,7R,E)-N-(but-2-enoyl)norushinsunine (5), and N-formyldehydrocaaverine (6) were isolated from the roots of Illigera luzonensis, together with 16 known compounds. Their structures were determined through spectroscopic and MS analyses. Among the isolates, (−)-deoxypodophyllotoxin (13) was the most cytotoxic, with IC₅₀ values of 0.0057, 0.0067, 0.00004, and 0.0035 μg/mL, respectively, against DLD-1, CCRF-CEM, HL-60, and IMR-32 cell lines. In addition, (−)-yatein (12) exhibited cytotoxic effects, with IC₅₀ values of 0.81, 0.20, and 0.59 μg/mL, respectively, against DLD-1, CCRF-CEM, and HL-60 cell lines.     

The first 1,3,2-diazabora-[3]ferrocenophanes - molecular structures and dynamic behaviour in solution

Dilithiated 1,1^′-bis(trimethylsilylamino)ferrocene (1) reacts with aminoboron dihalides (2) X₂B-N(R^′)R [X=Br, R^′=R=Et (2a); X=Cl, R^′=Me, R=CH₂Ph (2b), X=Cl, R^′=Et, R=Ph (2c)] to give 2-amino-1,3,2-diazabora-[3]ferrocenophanes (3a-c) for the first time. The steric constraints exerted by the [3]ferrocenophane unit and the presence of the N-SiMe₃ groups cause rather different B-N bonding situations in these tri(amino)boranes. The boron atom has the choice between three nitrogen atoms for BN(pp)π bonding: in the cases of 3a and 3b, it prefers the NEt₂ and the N(Me)CH₂Ph group, respectively, over the N-SiMe₃ groups, whereas in 3c the N(Et)Ph group appears to be the weaker π-donor. This can be concluded from the X-ray structural analyses carried out for 3a and 3c, and from the low temperature ¹H, ¹³C, and ²⁹Si NMR spectra of 3a-3c.     

Monoterpenoids from the aerial parts of Aruncus dioicus var. kamtschaticus and their antioxidant and cytotoxic activities

The aerial parts of Aruncus dioicus var. kamtschaticus afforded five new monoterpenoids (1-5): 4-(erythro-6,7-dihydroxy-9-methylpent-8-enyl)furan-2(5H)-one (1, aruncin A), 2-(8-ethoxy-8-methylpropylidene)-5-hydroxy-3,6-dihydro-2H-pyran-4-carboxylic acid (2, aruncin B), 4-(hydroxymethyl)-6-(8-methylprop-7-enyl)-5,6-dihydro-2H-pyran-2-one-11-O-β-d-glucopyranoside (3, aruncide A), (3S,4S,5R,10R)-3-(10-ethoxy-11-hydroxyethyl)-4-(5-hydroxy-7-methylbut-6-enyl)oxetan-2-one-11-O-β-d-glucopyranoside (4, aruncide B), and (3S,4S,5R,7R)-5-(9-methylprop-8-enyl)-1,6-dioxabicyclo[3,2,0]heptan-2-one-7-(hydroxymethyl)-12-O-β-d-glucopyranoside (5, aruncide C). Compound 2 showed potent cytotoxicity against Jurkat T cells with an IC₅₀ value of 17.15 μg/mL. In addition, compounds 7 and 10 exhibited moderate antioxidant activity with IC₅₀ values of 46.3 and 11.7 μM, respectively.     

Synthesis, structure, and reactivity of fluorous phosphorus/carbon/phosphorus pincer complexes derived from P(CH2)5P backbones

Reactions of the diphosphine H₂P(CH₂)₅PH₂ and fluorous alkenes H₂CCHR_fn (excess; R_fn = (CF₂)_n−1CF₃; n = a, 6; b, 8; c, 10) at 60 °C in the presence of AIBN give the precursors (R_fnCH₂CH₂)₂P(CH₂)₅P(CH₂CH₂R_fn)₂ (2a-c; 68-74%). These react with Pd(O₂CCF₃)₂ in CF₃C₆F₅ at 80 °C to give the title complexes (5a-c, 51-18%). Addition of LiCl to 5b gives (6b, 97%); subsequent reaction with MeLi affords the corresponding methyl complex (97%). A solvate of 6b is crystallographically characterized. The structure exhibits CH₂CH₂R_f8 groups with nearly anti C-C-C-C conformations, extending in parallel above and below the palladium square plane to create fluorous lattice domains. Reactions of 2b and other metal complexes are described; in the cases of (PhCN)₂PdCl₂ or (COD)₂PtCl₂ (CF₃C₆H₅, room temperature), bimetallic species in which two MCl₂ moieties are bridged by two diphosphines appear to form. The CF₃C₆F₁₁/toluene partition coefficients of 2a-c and 5a-c establish high fluorophilicities; despite the lower fluorine weight%, those of 5a-c are slightly greater ((97.4-99.7):(2.6-0.3) versus (95.3-99.3):(4.7-0.7)).     

Enzymatic resolution of albicanol and its application to the synthesis of (−)-copalic acid

The optical resolution of racemic albicanol (rac-1) based on the lipase-catalyzed transesterification by using vinyl myristate as an acyl donor afforded (8aR)-1 (99% ee) in 43% yield and (8aS)-1 (99% ee) in 37%. E value of the enzymatic reaction was 56.7 which was superior to that of the reported value (E = 25) by using isopropenyl acetate as an acyl donor. As the synthetic application of obtained (8aR)-1, (−)-copalic acid ((8aR)-3) and (−)-copalol ((8aR)-4) were synthesized from (8aR)-1 in 35% and 34% total yield, respectively.     

Crystal and molecular structures of substituted α-d-glucopyranosides

The crystal and molecular structures of methyl 2,4,6-tri-O-pivaloyl-α-d-glucopyranoside (1), methyl 4,6-O-(R)-benzylidene-2-O-pivaloyl-α-d-glucopyranoside (2), and methyl 4,6-O-(R)-benzylidene-2,3-di-O-pivaloyl-α-d-glucopyranoside (3) were determined by X-ray analysis. Crystals of 1 are orthorhombic, space group P2₁2₁2₁ with the unit cell a = 13.026(2), b = 16.832, c = 11.929(2) Å, Z = 4. Crystals of 2 are monoclinic, space group P2₁. The unit-cell parameters are a = 6.519(1), b = 14.664(4), c = 10.635(4) Å, β = 93.18(1)°, Z = 2. Crystals of 3 are orthorhombic, space group P2₁2₁2₁ with a = 10.006(3), b = 13.874(3), c = 18.527(5) Å, Z = 4. The structures were solved by MULTAN and refined by a full-matrix procedure to final values of R = 0.084 (1), 0.048 (2), and 0.069 (3). The pyranose ring in each compound adopts the ⁴C₁ conformation. The 1,3-dioxane rings in 2 and 3 show a chair conformation. The molecular packing in 1 is through the hydrogen bonds involving HO-3 and the 6-O-pivaloyl carbonyl group [HO-3 ⋯ O-9, 2.855(8) Å], which connect the molecules into a chain along

. The endocyclic oxygen atom is involved in an intermolecular hydrogen-bond with HO-3 [2.848(4) Å], joining molecules of 2 into the chains along

. There are no free hydroxyl groups in 3 and molecular packing reflects van der Waals interactions only.     

Ligand chirality-controlled selective formation of mono- and dinuclear copper complexes

Reaction of copper(II) acetate with the (S)-enantiomer of a tridentate binaphthyl Schiff base ligand, 2-(3,5-dichloro-2-hydroxybenzylideneamino)-2′-hydroxy-1,1′-binaphthyl (H₂L), in methanol afforded mononuclear copper(II) complex [Cu^II(HL)₂] ((S,S)-1) in 52% isolated yield. The same reaction gave dinuclear copper(II) complex [Cu^II₂(L)₂] ((R,S)-2) in 73% isolated yield when racemic-H₂L was used instead of (S)-H₂L. Both complexes (S,S)-1 and (R,S)-2 were characterized by elemental analysis, mass spectrometry, and X-ray crystallography. The present work highlights the functioning of ligand chirality as a ‘switch’ for selective formation of mono- and dinuclear metal complexes.     

Stereochemistry of cobalt-catalyzed carbonylation of 2-oxazolines

The stereospecificity of the title reaction is studied using the (4R,5S)-4-methyl-2,5-diphenyl-2-oxazoline and (4R,5R)-4-methyl-2,5-diphenyl-2-oxazoline as the substrates. While the catalyst system containing BnCo(CO)₄ and BnCOCo(CO)₄ (1) was used initially, a convenient catalyst formulation generated from the commercially available Co₂(CO)₈ and AIBN (2) has been found more effective than catalyst system 1. The stereoselectivity in all cases favors inversion at the C(5)-position with diastereomeric excess up to >97%.     

Facile route for the synthesis of the iminosugar nucleoside (3R,4R)-1-(pyren-1-yl)-4-(hydroxymethyl)pyrrolidin-3-ol

N-(Pyren-1-yl)-(3R,4S)-4-[(1S,2R)-1,2,3-trihydroxypropyl]pyrrolidin-3-ol (4) was obtained in 36% yield from 3-deoxy-3-C-formyl-1,2:5,6-di-O-isopropylidene-α-d-allofuranose (3) by combined hydrolysis and aminoalkylation reactions with 1-aminopyrene in a one-pot reaction. Cleavage reactions of the exocyclic triol chain in 4 with NaIO₄ and NaBH₄ resulted in iminosugars 7 and 8, which are analogues of the furanose forms of 2-deoxy-d-allose and of 2-deoxy-d-ribose, the latter analogue N-(pyren-1-yl)-(3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol (8) being formed in 83% yield.     

An efficient lipase-catalyzed enantioselective hydrolysis of (R,S)-azolides derived from N-protected proline, pipecolic acid, and nipecotic acid

In the Candida antarctica lipase B-catalyzed hydrolysis of (R,S)-azolides derived from (R,S)-N-protected proline in water-saturated methyl tert-butyl ether (MTBE), high enzyme activity with excellent enantioselectivity (V _S V _R ^?1 ?>?100) for (R,S)-N-Cbz-proline 1,2,4-triazolide (1) and (R,S)-N-Cbz-proline 4-bromopyrazolide (2) was exploited in comparison with their corresponding methyl ester analog (3). Changing of the substrate structure, water content, solvent, and temperature was found to have profound influences on the lipase performance. On the basis of enzyme activity and enantioselectivity and solvent boiling point, the best reaction condition of using 1 as the substrate in water-saturated MTBE at 45 °C was selected and further employed for the successful resolution of (R,S)-N-Cbz-pipecolic 1,2,4-triazolide (5) and (R,S)-N-Boc-nipecotic 1,2,4-triazolide (9). Moreover, more than 89.1 % recovery of remained (R)-1 is obtainable in five cycles of enzyme reusage, when pH 7 phosphate buffers were employed as the extract at 4 °C.     

Cyclic and high molecular weight chiral binaphthoxy-phosphazene polymers carrying Br or trimethylsilyl-acetylene groups

The new chiral and functionalized cyclic binaphthoxyphosphazenes R,R,R-[N₃P₃(O₂C₂₀H₁₀Br₂)₃] (R-1), R,R,R-[N₃P₃(O₂C₂₀H₁₀(CCSiMe₃)₂)₃] (R-2), and the high molecular weight linear polymers R/S-[NP(O₂C₂₀H₁₀Br₂)]_n (R/S-3), R-[NP(O₂C₂₀H₁₀Br₂)]_n (R-3), and R-{NP[O₂C₂₀H₁₀(CCSiMe₃)₂]}_n, (R-4), with M_w on the order of 10⁶ and very high T_g, have been synthesized and characterized by IR and NMR spectroscopy. The optically active polymer (R-3) was configurationally stable below 300 °C, but at higher temperatures an atropisomerization process took place that became faster near the glass transition temperature (ca. 350 °C).     

Reactivity of platina-β-diketones towards chelating nitrogen and sulfur donors: formation of acyl(hydrido)platinum(IV) and acyl(chloro)platinum(II) complexes

The platina-β-diketone [Pt₂{(COMe)₂H}₂(μ-Cl)₂] (1) was found to react with chelating N,N-ligands 2(R^′NCR)C₅H₄N (R/R^′=Ph/OH, H/Ph, Me/Ph) to form acyl(hydrido)platinum(IV) complexes [Pt(COMe)₂Cl(H){2-(R^′NCR)C₅H₄N}] (R/R^′=Ph/OH 2a; H/Ph 2b; Me/Ph (2c)). Reactions of complex 1 with chelating S,S- and N,S-donors (RS-CH₂-CH₂-SR, 2-(RSCH₂)C₅H₄N, R=Et, Ph, t-Bu) afforded acyl(chloro)platinum(II) complexes [Pt(COMe)Cl(RSCH₂CH₂SR)] (R=Et, 3a; Ph, 3b; t-Bu, 3c) and [Pt(COMe)Cl{2-(RSCH₂)C₅H₄N}] (R=Et, 4a; Ph, 4b; t-Bu, 4c), respectively. All complexes were fully characterized by microanalysis, IR and NMR (¹H, ¹³C) spectroscopy. Furthermore, molecular structures of complexes 3b and 4b were determined by single-crystal X-ray diffraction analyses revealing close to square-planar configuration. In complex 4b the acetyl ligand is trans to pyridine N atom (configuration index SP-4-2). The reactions are discussed in terms of consecutive oxidative addition and reductive elimination reactions.     

Synthesis, reactivities and catalytic carbonylation of rhodium(I) carbonyl complexes containing isomeric acetylpyridine ligands

[Rh(CO)₂Cl]₂ reacts with two mole equivalent of 2-acetylpyridine (a), 3-acetylpyridine (b) and 4-acetylpyridine (c) to afford chelate [Rh(CO)Cl(η²-N∩O)] (1a) and non-chelate [Rh(CO)₂Cl(η¹-N∼O)] (1b, 1c) complexes, where, N∩O = a, N∼O = b, c. Oxidative addition (OA) of 1a-1c with CH₃I and C₂H₅I yields penta coordinate rhodium(III) complexes, [Rh(COR)ClI(η²-N∩O)] {R = -CH₃ (2a); -C₂H₅ (3a)} and [Rh(COR)(CO)ClI(η¹-N∼O)] {R = -CH₃ (2b, 2c); -C₂H₅ (3b, 3c)}. Kinetic study for the reaction of 1a-1c with CH₃I indicates a pseudo-first order reaction. The catalytic activity of 1a-1c for the carbonylation of methanol to acetic acid and its ester was evaluated at different initial CO pressures 5, 10 and 20 bar at ∼25 °C and higher turn over numbers (TON = 1581-1654) were obtained compared to commercial Monsanto’s species [Rh(CO)₂I₂]⁻ (TON = 1000) under the reaction conditions: temperature = 130 ± 1 °C, pressure = 15-32 bar, rpm = 450, time = 1 h and catalyst: substrate = 1: 1900.     

2-(1-(Dimethylamino)ethyl)phenylpalladium(II) complexes 5-functionalized with fluorous silyl tails

New fluorous-organometallics based on the chiral ligand α-methyl-N,N-dimethylbenzylamine (TMBA) were prepared by treatment of fluorous silyl bromide reagents with in situ 4-lithiated TMBA to give fluorous N,N-dimethyl(α-methyl-4-trialkylsilylbenzyl)amine ligands 1a-1c that vary in the number of fluorous tails attached to the Si atom. Ligands 1a-1c were successfully cyclo-palladated by treatment with Pd(OAc)₂/LiCl in methanol to furnish the corresponding chloride-bridged dimeric arylpalladium(II) complexes 2a-2c in good yields. The latter derivatives could be converted into monomeric Lewis-base adducts by complexation with pyridine (3a-3c), or triphenylphosphine (4a-4c). The crystal structure of triphenylphosphine complex 4a has been elucidated. To probe their fluorophilicity, the partition coefficient of each of the derivatives in the fluorous biphasic solvent (FBS) system perfluoromethylcyclohexane/n-octane has been determined.     

Dicarbonyliridium(I) complexes of pyridine ester ligands and their reactivity towards various electrophiles

The reaction of dimeric precursor [Ir(CO)₂Cl]₂ with two molar equivalent of the pyridine-ester ligands (L) like methyl picolinate (a), ethyl picolinate (b), methyl nicotinate (c), ethyl nicotinate (d), methyl isonicotinate (e) and ethyl isonicotinate (f) affords the tetra coordinated neutral complexes of the type [Ir(CO)₂ClL] (1a-f). The single crystal X-ray structure of 1d reveals that the Ir atom occupies the centre of an approximately square planar geometry with two CO groups cis- to each other. Intermolecular C-H?O and Ir?C interactions greatly stabilize the supramolecular structure of 1d in the solid state. The oxidative addition (OA) reactions of 1a-f with different electrophiles such as CH₃I, C₂H₅I and I₂ undergo decarbonylation of one CO group to generate the oxidized products of the type [Ir(CO)RClIL] where R = -CH₃ (2a-f); -C₂H₅ (3a-f) and [Ir(CO)ClI₂L] (4a-f). Kinetic study of the reaction of 1c-f with CH₃I indicates a first order reaction which follow the order 1d > 1c > 1f > 1e. All the synthesized complexes were characterized by elemental analyses, IR, and multinuclear NMR spectroscopy.