Diastereoselective reduction of β-keto carbonyl compounds by cultured plant cells

The diastereoselective reduction of β-keto carbonyl compounds such as 2-benzamidomethyl-3-oxobutanoates and 2-methyl-2-(2-propenyl)cyclopentan-1,3-dione by cultured cells of higher plants was investigated. The reduction of the 2-benzamidomethyl-3-oxobutanoates by Parthenocissus tricuspidata diastereoselectively produced the (2R,3S)-2-benzamidomethyl-3-hydroxybutanoates, whereas the reduction by Gossypium hirsutum gave the (2S,3S)-2-benzamidomethyl-3-hydroxybutanoates. The (2R,3S)/(2S,3S) predominance in the reduction with Nicotiana tabacum, Glycine max, and Catharanthus roseus was reversed by the change in the structure of the alkoxyl group in the substrate. On the other hand, the reduction of 2-methyl-2-(2-propenyl)cyclopentan-1,3-dione by P. tricuspidata produced (2R,3S)-3-hydroxy-2-methyl-2-(2-propenyl)cyclopentan-1-one, whereas the reaction by N. tabacum, G. max, C. roseus, and G. hirsutum gave (2S,3S)-3-hydroxy-2-methyl-2-(2-propenyl)cyclopentan-1-one.     

Synthesis of 5H-pyridazino[4,5-b]indoles and their benzofurane analogues utilizing an intramolecular Heck-type reaction

The title ring systems were prepared from pyridazin-3(2H)-one precursors in novel, efficient pathways. 2-Methylbenzo[b]furo[2,3-d]pyridazin-1(2H)-one was synthesized via a regioselective nucleophilic substitution reaction of a 2-methyl-4,5-dihalopyridazin-3(2H)-one with phenol followed by an intramolecular Heck-type reaction. The same molecule and its 6-phenyl analogue were also prepared via reaction of 2-methyl-5-iodopyridazin-3(2H)-one or 2-methyl-5-chloro-6-phenylpyridazin-3(2H)-one, respectively, with 2-bromophenol or 2-iodophenol followed by Pd-catalyzed cyclodehydrohalogenation. Moreover, a new approach for the synthesis of 2-methyl-2,5-dihydro-1H-pyridazino[4,5-b]indol-1-ones was also elaborated utilizing a Heck-type ring closure reaction on 5-[(2-bromophenyl)amino]-2-methylpyridazin-3(2H)-ones which were obtained via Buchwald-Hartwig amination of 2-methyl-5-halopyridazin-3(2H)-ones with 2-bromoaniline.     

Green aldose isomerisation: 2-C-methyl-1,4-lactones from the reaction of Amadori ketoses with calcium hydroxide

Saccharinic acids, branched 2-C-methyl-aldonic acids, may be accessed via a green procedure from aldoses by sequential conversion to an Amadori ketose and treatment with calcium hydroxide; d-galactose and d-glucose are converted to 2-C-methyl-d-lyxono-1,4-lactone (with a small amount of 2-C-methyl-d-xylono-1,4-lactone) and 2-C-methyl-d-ribono-1,4-lactone. Inversion of configuration at C-4 of the branched lactones allows access to 2-C-methyl-l-ribono-1,4-lactone and 2-C-methyl-l-lyxono-1,4-lactone, respectively. d-Xylose affords 2-C-methyl-d-threono-1,4-lactone and 2-C-methyl-d-erythrono-1,4-lactone, whereas l-arabinose, under similar conditions, gave the enantiomers 2-C-methyl-l-threono-1,4-lactone and 2-C-methyl-l-erythrono-1,4-lactone.     

Ring size and substituent steric effects in cyclic ketene-N,O/S-acetal trifluoroacetylations

Trifluoroacetylations of cyclic ketene-N,O/S-acetals exhibit a ring size effect. The five-membered rings 2,4,4-trimethyl-2-oxazoline, 2-methyl-2-oxazoline, and 2-methyl-2-thiazoline, each form cyclic ketene-N,O/S-acetal intermediates which then react with trifluoroacetic anhydride to give β-monotrifluoroacetylation products. Conversely, the six-membered ring 2-methyl-2-oxazine gives its β,β-bistrifluoroacetylation product. In situ-generated five-membered ring N-Me cyclic ketene-N,O-acetals, 3,4,4-trimethyl-2-methylene-oxazolidine, and 3-methyl-2-methylene-oxazolidine, and six-membered ring 3-methyl-2-methylene-1,3-oxazinane were each β,β-bistrifluoroacetylated. However, 3-methyl-2-methylene-oxazolidine also afforded a γ-lactam by an iodide-catalyzed rearrangement of its β,β-bistrifluoroacetylated derivative. In situ-generated 3-methyl-2-methylene-thiazolidine gives both β-mono- and β,β-bistrifluoroacetylation products and no lactam, in contrast to its N,O-analog 3-methyl-2-methyleneoxazolidine.     

Regioselective biocatalytic hydrolysis of (E,Z)-2-methyl-2-butenenitrile for production of (E)-2-methyl-2-butenoic acid

Acidovorax facilis 72W nitrilase catalyzed the regioselective hydrolysis of (E,Z)-2-methyl-2-butenenitrile, producing only (E)-2-methyl-2-butenoic acid with no detectable conversion of (Z)-2-methyl-2-butenenitrile. (E)-2-Methyl-2-butenoic acid, produced in aqueous solution as the ammonium salt, was readily separated from (Z)-2-methyl-2-butenenitrile, and isolated in high yield and purity. The combination of nitrile hydratase and amidase activities of several Comamonas testosteroni strains were also highly regioselective for the production of (E)-2-methyl-2-butenoic acid from (E,Z)-2-methyl-2-butenenitrile.     

Lanthanide N,N′-piperazine-bis(methylenephosphonates) (Ln=La, Ce, Nd) that display flexible frameworks, reversible hydration and cation exchange

Hydrothermal syntheses of lanthanide bisphosphonate metal organic frameworks comprising the light lanthanides lanthanum, cerium and neodymium and N,N′-piperazine bis(methylenephosphonic acid) (H₂L(1) and its 2-methyl and 2,5-dimethyl derivatives (H₂L(2) and H₂L(3)) gives three new structure types. At elevated starting pH (ca. 5 and above) syntheses give ‘type I’ materials with all metals and acids of the study (MLnLxH₂O, M=Na, K, Cs; Ln=La, Ce, Nd; x≈4: KCeL(1)·4H₂O, C2/c, a=23.5864(2) Å, b=12.1186(2) Å, c=5.6613(2) Å, β=93.040(2)°). The framework of structure type I shows considerable flexibility as the ligand is changed, due mainly to rotation around the -N-CH₂- bond of the linker in response to steric considerations. Type I materials demonstrate cation exchange and dehydration and rehydration behaviour. Upon dehydration of KCeL·4H₂O, the space group changes to P2₁/n, a=21.8361(12) Å, b=9.3519(4) Å, c=5.5629(3) Å, β=96.560(4)°, as a result of a change of the piperazine ring from chair to boat configuration. When syntheses are performed at lower pH, two other structure types crystallise. With the ‘non-methyl’ ligand 1, type II materials result (LnL(1)H₂L(1)·4.5H₂O: Ln=La, P−1, a=5.7630(13) Å, b=10.213(2) Å, c=11.649(2) Å, α=84.242(2)°, β=89.051(2)°, γ=82.876(2)°) in which one half of the ligands coordinate via the piperazine nitrogen atoms. With the 2-methyl ligand, structure type III crystallises (LnHL(2)·4H₂O: Ln=Nd, Ce, P2₁/c, a=5.7540(9) Å, b=14.1259(18) Å, c=21.156(5) Å, β=90.14(2)°) due to unfavourable steric interactions of the methyl group in structure type II.     

A mild and efficient cyanosilylation of ketones catalyzed by a Lewis acid-Lewis base bifunctional catalyst

A new family of bifunctional catalysts (N-oxides-Ti(OⁱPr)₄ (2:1)) containing a Lewis acid and a Lewis base was developed and applied to the catalytic cyanosilylation of ketones. Utilizing rac((1R,2S) and (1S,2R))-1-(2′-pyridylmethyl)-2-diphenylhydroxymethylpyrrolidine N-oxide-titanium (2:1) complex and N-benzyl-diethanolamine N-oxide-titanium (2:1) complex as catalysts, the cyanosilylation products were obtained in 42-97% yield. Based on experimental phenomena and kinetic studies, a catalytic cycle was proposed to explain the remarkable activities of these catalysts. Investigations indicated that rac((1R,2S) and (1S,2R))-1-(2′-pyridylmethyl)-2-diphenylhydroxymethylpyrrolidine N-oxide-titanium (2:1) complex and N-benzyl-diethanolamine N-oxide-titanium (2:1) complex should promote the reaction via a dual activation of the ketone by the titanium and TMSCN by the N-oxide.     

Reactivity of 2-halo-2H-azirines. Part 3: Dehalogenation of 2-halo-2H-azirine-2-carboxylates

The dehalogenation of 2-halo-3-phenyl-2H-azirine-2-carboxylates is described. Using sodium borohydride and tributyltin hydride 3-phenyl-2H-azirine-2-carboxylates were obtained in moderate yields. The synthesis of a new 2-bromo-2H-azirines with a chiral auxiliary, 10-phenylsulfonylisobornyl 2-bromo-3-phenyl-2H-azirine-2-carboxylate, is reported. Its dehalogenation led to 10-phenylsulfonylisobornyl 2H-azirine-2-carboxylate as single stereoisomer together with the formation of 10-phenylsulfonylisobornyl acetate.     

Novel pyrrolo[1,2-a][3.1.6]benzothiadiazocine ring synthesis. Unusual Truce-Smiles type rearrangement of 1-{[1-(2-nitrophenyl)-1H-pyrrol-2-yl]sulfonyl(or sulfinyl)}acetone

Reaction of 1-{[1-(2-nitrophenyl)-1H-pyrrol-2-yl]sulfonyl}acetone with sodium hydroxide with or without zinc gave 1-(2-nitrophenyl)(1H-pyrrol-2-ylsulfonyl)methane by a Truce-Smiles type of transformation and 1-(2-nitrophenyl)-2-methylsulfonylpyrrole by deacetylation. Similar treatment of 1-{[1-(2-nitrophenyl)-1H-pyrrol-2-yl]sulfinyl}acetone gave only 1-(2-nitro-phenyl)(1H-pyrrol-2-ylsulfinyl)methane. 1-{[1-(2-Nitrophenyl)-1H-pyrrol-2-yl]sulfanyl}acetone, 2-{[1-(2-nitrophenyl)-1H-pyrrol-2-yl]sulfanyl}-1-phenyl-ethan-1-one or 2-{[1-(2-nitrophenyl)-1H-pyrrol-2-yl]sulfanyl}acetonitrile were reductively cyclised with sodium borohydride and 5% palladium-on-carbon into 6-methyl(or phenyl)-5,6-dihydro-7H-pyrrolo[1,2-a][3.1.6]benzothiadiazocin-7-ol or 6-amino-5H-pyrrolo[1,2-a][3.1.6]benzothiadiazocine-7-oxide, respectively.     

Structural studies of five layer Aurivillius oxides: A2Bi4Ti5O18 (A=Ca, Sr, Ba and Pb)

The room temperature structures of the five layer Aurivillius phases A₂Bi₄Ti₅O₁₈ (A=Ca, Sr, Ba and Pb) have been refined from powder neutron diffraction data using the Rietveld method. The structures consist of [Bi₂O₂]²⁺ layers interleaved with perovskite-like [A₂Bi₂Ti₅O₁₆]²⁻ blocks. The structures were refined in the orthorhombic space group B2eb (SG. No. 41), Z=4, and the unit cell parameters of the oxides are a=5.4251(2), b=5.4034(1), c=48.486(1); a=5.4650(2), b=5.4625(3), c=48.852(1); a=5.4988(3), b=5.4980(4), c=50.352(1); a=5.4701(2), b=5.4577(2), c=49.643(1) for A=Ca, Sr, Ba and Pb, respectively. The structural features of the compounds were found similar to n=2-4 layers bismuth oxides. The strain caused by mismatch of cell parameter requirements for the [Bi₂O₂]²⁺ layers and perovskite-like [A₂Bi₂Ti₅O₁₆]²⁻ blocks were relieved by tilting of the TiO₆ octahedra. Variable temperature synchrotron X-ray studies for Ca and Pb compounds showed that the orthorhombic structure persisted up to 675 and 475 K, respectively. Raman spectra of the compounds are also presented.     

Synthesis and structural study of tetrahydroindazolones

Multinuclear magnetic resonance spectroscopy allowed us to characterize four 1(2),5,6,7-tetrahydro-4H-indazol-4-one derivatives (1-4) and establish the most stable tautomer in each case. The crystal structure of 6,6-dimethyl-1(2),5,6,7-tetrahydro-4H-indazol-4-one (2) (orthorhombic space group P2(1)2(1)2(1), a=10.1243(8), b=21.526(2), c=24.992(2) Å, Z=4, 293 K) presents two different trimers, bonded through N-H?N hydrogen bonds involving tautomers 1H and 2H. In crystalline 3,6,6-trimethyl-2,5,6,7-tetrahydro-4H-indazol-4-one (4) (monoclinic space group P2(1)/c, a=5.9827(7), b=16.494(2), c=11.012(1) Å, β=93.464(2)°, Z=4, 293 K) only tautomer 2H exists forming a hydrogen-bonded network through the 4-oxo group and a water molecule.     

Fuzzy Symmetry Characteristics of Propadine Molecule

The fuzzy symmetry characteristics for the internal-rotation of propadine were analyzed using the fuzzy symmetry theory for molecule and molecular orbital (MO). In the process of rotation, three different symmetry point groups D_2h, D_2d, and D₂ were considered. Using the D_4h point group, which is the minimal point group including all symmetry elements of D_2h, D_2d, and D₂, we can analyze the fuzzy symmetry for this process. The elements included in D_4h point group can be classified to four subsets: (i) G0—it includes all the elements in D₂ point group, also belongs to all the above three point groups of D_2h, D_2d, and D₂; (ii) G1—it includes the elements in D_2h point group, but not in D_2d point group; (iii) G2—it includes the elements in D_2d point group, but not in D_2h point group; (iv) G3—it includes the elements in D_4h point group, but not in D_2h or D_2d point group. On the basis of the above four subsets, we analyzed the membership functions and the regularity of variation in MOs for the internal-rotation of propadine.     

A novel dynamic kinetic resolution accompanied by intramolecular transesterification: asymmetric synthesis of a 4-hydroxymethyl-2-oxazolidinone from serinol derivatives

Reaction paths of the one-pot reaction of (R)-2-(α-methylbenzyl)amino-1,3-propanediol (1) and 2-chloroethyl chloroformate with DBU giving (4S,αR)-4-hydroxymethyl-3-(α-methylbenzyl)-2-oxazolidinone [(4S)-2] (94% de) were investigated. Intermediates of this reaction, 2-chloroethyl (2S)- and 2-chloroethyl (2R)-3-hydroxy-2-[(αR)-α-methylbenzyl]aminopropyl carbonates [(2S)-4 and (2R)-4], were synthesized individually. After the addition of DBU to the respective solution of the carbonate (2S)-4 and that of (2R)-4 in dichloromethane, the intramolecular transesterification between (2S)-4 and (2R)-4 and the diastereoselective intramolecular cyclization proceeded to afford (4S)-2 in high diastereomeric excess. Therefore, two monocarbonates (2S)-4 and (2R)-4 were kinetically resolved by this cyclization during the intramolecular transesterification between (2S)-4 and (2R)-4. We found that this process involved dynamic kinetic resolution accompanied by intramolecular transesterification.     

Studies towards the synthesis of (1R,2S)- and (1S,2S)-1,2-epoxy-3-hydroxypropylphosphonates and (1S,2S)- and (1R,2S)-2,3-epoxy-1-hydroxypropylphosphonates

The trans-configured fosfomycin analogue, diethyl (1S,2S)-1,2-epoxy-3-hydroxypropylphosphonate, was synthesised by the intramolecular Williamson reaction of diethyl (1S,2R)-1,3-dihydroxy-2-mesyloxypropylphosphonate. The cis-analogue was obtained as O-ethyl or O,O-diethyl (1R,2S)-1,2-epoxy-3-hydroxypropylphosphonates, when (1R,2R)-1,3-dihydroxy-2-mesyloxypropylphosphonate or its 3-O-trityl derivative were used as starting materials, respectively. The intramolecular Williamson cyclisations of diethyl (1S,2R)- and (1R,2S)-1-benzyloxy-3-hydroxy-2-mesyloxypropylphosphonates led to diethyl (1S,2S)- and (1R,2S)-2,3-epoxy-1-benzyloxypropylphosphonates, respectively, with the concomitant formation of diethyl (E)-1-benzyloxy-3-hydroxyprop-1-en-1-phosphonate. From diethyl (1S,2S)- and (1R,2S)-2,3-epoxy-1-benzyloxypropylphosphonates, enantiomerically pure diethyl (1S,2S)- and (1R,2S)-1,2-dihydroxypropylphosphonates were obtained by catalytic hydrogenation, while diethyl (1S,2S)- and (1R,2S)-3-acetamido-1,2-dihydroxypropylphosphonates were produced after epoxide ring opening with dibenzylamine, acetylation and hydrogenolysis.     

Selective reactions of α-aryl wittig reagents with the formyl moiety of 4-formylbenzoyl chloride

The benzylic Wittig reagents 2a, 2b and 2e react with 4-formylbenzoyl chloride 1 to give 40–60% yields of products 3 derived from selective attack at the formyl group of 1; The same selectivity is not found for the non-stabilized ylids 2c and 2d or the stabilized ylid 2f.     

2-Polyfluoroalkyl thiopyrylium salts: synthesis and reactions with nucleophiles

2-Polyfluoroalkylthiopyrylium salts have been synthesized by oxidative aromatization of 2-polyfluoroalkyl-2H-thiopyrans with triphenylmethane tetrafluoroborate. Nucleophilic addition of methanol, sodium azide, or urea to 2-trifluoromethylthiopyrylium tetrafluoroborate in a basic medium proceeds at the α-position to give the corresponding 2-substituted 6-trifluoromethyl-2H-thiopyrans whereas imidazoles, fluorine-containing 1,2,3-triazole, potassium thiolacetate, and sodium nitromethane afford mixtures of 2H- and 4H-thiopyrans. cis-Dihydroxylation of 6-trifluoromethyl-2-methoxy-2H-thiopyran affords the fluorine-containing thiohexenopyranoside derivative 8.     

Synthesis and characterization of ruthenium p-cymene complexes bearing bidentate P–N and E–N ligands (E = S,Se) based on 2-aminopyridine

The syntheses and characterization of a series of cationic of Ru(II) halfsandwich complexes of the types [Ru(η⁶-p-cymene)(κ²(P,N)-PN)Cl]⁺ (PN = N-diphenylphosphino-2-aminopyridine, N-di-iso-propylphosphino-2-aminopyridine, 2-[(2-pyridyl)amino]dibenzo[d,f][1,2,3]dioxaphosphepine, N-(diisopropylphosphino)-2,6-diaminopyridine) and [Ru(η⁶-p-cymene)(κ²(E,N)-EN)Cl]⁺ (EN = N-(2-pyridinyl)amino-diphenylphosphine sulfide, N-(2-pyridinyl)amino-diisopropylphosphine sulfide, N-(2-pyridinyl)amino-diphenylphosphine selenide, N-(2-pyridinyl)amino-diisopropylphosphine selenide) is described. Some of these complexes were tested as precatalysts for the transfer hydrogenation of acetophenone to give 1-phenyl ethanol.     

Mono and dinuclear palladium complexes of o-alkyl substituted arylphosphane ligands: Solvent-dependent syntheses, NMR-spectroscopic characterization and X-ray crystallographic studies

Palladium(II) chloride complexes of o-alkyl substituted phosphanes were prepared in various solvents with the phosphane ligands o-methylphenyldiphenylphosphane, o-ethylphenyldiphenylphosphane, o-isopropylphenyldiphenylphosphane, o-cyclohexylphenyldiphenylphosphane and o-phenylphenyldiphenylphosphane. The structures of the complexes were characterized by ¹H NMR and ³¹P NMR spectroscopy and elemental analysis. The X-ray structures of PdCl₂(o-methylphenyldiphenylphosphane)₂, PdCl₂(o-isopropylphenyldiphenylphosphane)₂, PdCl₂(o-cyclohexylphenyldiphenylphosphane)₂, PdCl₂(o-phenylphenyldiphenylphosphane)₂, [PdCl₂(o-methylphenyldiphenylphosphane)]₂, [PdCl₂(o-ethylphenyldiphenylphosphane)]₂ and [PdCl₂(o-cyclohexylphenyldiphenylphosphane)]₂ were also determined. We report a systematic, solvent-dependent method to prepare palladium(II) complexes of the aryl phosphines o-methylphenyldiphenylphosphane, o-cyclohexylphenyldiphenylphosphane and o-phenylphenyldiphenylphosphane with a desired nuclearity. We demonstrated that chlorinated solvents promote the formation of dinuclear chlorine-bridged palladium complexes for all five ligands. The ligands preferentially form mononuclear palladium complexes in other solvents where the starting materials are only weakly soluble in the solvent.     

Synthesis of 2′-deoxy-5-fluoro-5′-O-1″,3″,2″-oxazaphosphacyclohexa-2″-yluridine 2″-oxide and related compounds

2′,3′-O-Isopropylidene-5′-O-1″,3″,2″-oxazaphosphacyclohex-2″-yl-uridine 2″-oxide has been obtained by the action of phosphoryl chloride and N-methylmorpholine, followed by 3-aminopropan-1-ol, on 2',3'-O-isopropy-lidineuridine. A similar reaction carried out on 3'-O-acetylthymidine, followed by removal of the acetyl group gave 5′-O-1″,3″,2″-oxazaphospha-2″-yl-thymidine 2″-oxide. Both of these compounds were obtained more conveniently by treatment of 2',3'-O-isopropylideneuridine and thymidine respectively with 2-chloro-1,3,2-oxazaphosphacyclo-hexane 2-oxide in pyridine. Similar treatment of 2′-deoxy-5-fluorouridine gave 2′-deoxy-5-fluoro-5′-O-1″,3″,2″-oxazaphosphacyclohex-2″-yluridine 2″-oxide. The latter compound was tested for activity against S 180 Crocker sarcoma and L 1210 mouse leukaemia. Only a marginal activity against the S 180 sarcoma was detected. However inactivity of the compound in inducing leukopenia indicated that it might be of low toxicity and that further testing of the compound would be justified.     

A new Kdo derivative for the synthesis of an inner-core disaccharide of lipopolysaccharides and lopooligosaccharides

Methyl (7,8-di-O-benzoyl-4,5-O-isopropylidene-3-deoxy-d-manno-2-oct-ulopyranoside)onate was found to be a useful new intermediate in the synthesis of an inner-core oligosaccharide of lipooligosaccharides and lipopolysaccharides produced by gram-negative bacteria. This intermediate could be converted to the corresponding glycosyl fluoride and 4,5-diol acceptor with ease. Syntheses of dimeric Kdo, O-(sodium 3-deoxy-α-d-manno-2-octuropyranosylonate)-(2-4)-sodium (allyl 3-deoxy-α-d-manno-2-octuropyranoside)onate, and O-(sodium 3-deoxy-α-d-manno-2-octuropyranosylonate)-(2-8)-sodium (allyl 3-deoxy-α-d-manno-2-octuropyranoside)onate were successfully demonstrated.