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Chiral intermediates were prepared by biocatalytic processes for the chemical synthesis of four pharmaceutical drug candidates. These include: (i) the microbial reduction of 3,5-dioxo-6-(benzyloxy) hexanoic ethyl ester to (3S,5R)-dihydroxy-6-(benzyloxy) hexanoic acid ethyl ester, an intermediate for a new anticholesterol drug; (ii) synthesis of (2R,3S)-(-)-N-benzoyl-3-phenyl isoserine ethyl ester, a taxol side-chain synthon; (iii) the microbial oxygenation of 2,2-dimethyl-2H-1-benzopyran-6-carbonitrile to the corresponding (3S,4S) epoxide and (3S,4R)-trans diol, intermediates for synthesis of potassium channel opener; (iv) the biotransformation of (exo,exo)-7-oxabicyclo [2.2.1] heptane-2,3-dimethanol to the corresponding chiral lactol and lactone, intermediates for thromboxane A2 antagonist.

An efficient biocatalytic process has been developed for the resolution of methyl (1 RS )- N - t Boc-6-hydroxy-3,4-dihydro-1 H -isoquinoline-1-carboxylate rac - 1 by means of Seaprose S-mediated enantioselective hydrolysis to afford (1 S )- 2 and (1 R )- 1 in 87% and 93% isolated yield, 101% and 96% potency, and ee >99.8% and >99.5%, respectively.

An efficient biocatalytic process has been developed for the resolution of 1-(3′-bromophenyl)ethylamine ( RS )- 1 by way of enantioselective lipase-mediated ( R )-selective acylation with ethyl 2-methoxyacetate to afford ( S )-amine ( S )- 1 and ( R )-2″-methoxyacetamide (( R )- 2 ) in 91–95% and 90–92% isolated yield, respectively, and both with >99% ee.

Microbial reduction of ethyl 1-benzyl-3-oxo-piperidine-4-carboxylate by the majority of evaluated microorganisms gave the ethyl cis-(3R,4R)-1-benzyl-3R-hydroxy-piperidine-4R-carboxylate as the major product in high diastereo- and enantioselectivities. The 3R,4R-hydroxy ester was produced in 97.4% diastereomeric excess (de) and 99.8% enantiomeric excess (ee) by Candida parapsilosis SC16347, while 99.5% de and 98.2% ee were obtained from reduction by Pichia methanolica SC16415. A few of the evaluated microorganisms gave 10–40% of the ethyl trans-(3R,4S)-1-benzyl-3R-hydroxy-piperidine-4S-carboxylate as the minor product.

Previously we have demonstrated the reduction of ethyl diketoester 4 to the corresponding dihydroxy ester 6a by Acinetobacter sp. SC13874. Recently we screened more than 100 cultures for microbial reduction of both the ethyl and t-butyl diketoesters 4 and 5. Most yeast cultures showed a preference for reduction at the C-3 with low enantioselectivity. Among the three Acinetobacter strains screened, Acinetobacter sp. SC13874 reduced both compounds 4 and 5 to the corresponding (3R)- and (5S)-monohydroxy compounds. Monohydroxy compounds were isolated and their absolute configurations determined. (3R)- and (5S)-Monohydroxy compounds were reduced further to the corresponding dihydroxy esters 6a and 8a to provide alternate routes for the synthesis of compounds 14a and 16a, potential intermediates for the synthesis of HMG-CoA reductase inhibitors. Cell suspensions of Acinetobacter sp. SC13874 reduced the ethyl diketoester 4 to a mixture of desired syn and undesired anti diastereomers. The desired syn-(3R,5S)-dihydroxy ester 6a was obtained with an enantiomeric excess (ee) of 99% and a diastereomeric excess (de) of 63%. Cell suspensions reduced the t-butyl diketoester 5 to a mixture of mono- and dihydroxy esters with the dihydroxy ester showing an ee of 87% and de of 51% for the desired syn-(3R,5S)-dihydroxy ester 8a. Three different ketoreductases were purified to homogeneity, and their biochemical properties compared. Reductase I only catalyzes the reduction of ethyl diketoester 4 to its monohydroxy products 10 and 11, whereas reductase II catalyzes the formation of dihydroxy products 6 and 7 from monohydroxy substrates 10 and 11. A third reductase (III) was identified, which catalyzes the reduction of diketoester 4 to syn-(3R,5S)-dihydroxy ester 6a.

Enantioselective asymmetric hydrolysis of (1α,2β,3α)-2-(benzyloxymethyl)-cyclopent-4-ene-1,3-diol diacetate 1 to the corresponding (+)-monoacetate 2 was carried out using lipase PS-30 from Pseudomonas cepacia or pancreatin. A reaction yield of 85 M % with an enantiomeric excess (ee) of 98% was obtained. Using pancreatin, a reaction yield of 75 M % with an ee of 98.5% was obtained. Asymmetric acetylation of (1α,2β,3α)-2-(benzyloxymethyl)-cyclopent-4-ene-1,3-diol 3 to the corresponding (−)-monoacetate 4 was carried out using lipase PS-30 with isopropenyl acetate as the acylating agent. A reaction yield of 80 M % with an ee of 98% was obtained for (−)-monoacetate 4 .

Electrospray ionization (ESI) quadrupole ion trap mass spectrometry (QIT-MS) and collisionally activated dissociation (CAD) were used to evaluate the rare-earth binding properties of two hydrophobic carbamoylmethylphosphine oxide (CMPO) ligands, the normal bidentate variety, (t-BuC6H4)2P(O)CH2C(O)N(i-Bu)2 (A), a new potentially tridentate extractant, (t-BuC6H4)2P(O)CH[CH2C(O)N(i-Bu)2]C(O)N(i-Bu)2 (B), and tributyl phosphate. The mass spectral results obtained from analysis of 1% HNO3/methanol solution containing the ligands and dissolved lanthanide salts reveal that the favorable stoichiometries of the ligand/metal/nitrate complexes are 2:1:2 for the bidentate ligand A, 1:1:2 for the tridentate ligand B, and 3:1:2 for the monodentate tributyl phosphate. These observed stoichiometries correlate with the number of available binding sites on each ligand as well as with potential steric effects. Energy-variable collisionally activated dissociation experiments showed that for the 2:1:2 complexes involving ligand A or B, as the ionic radius of the bound metal decreased, the removal of nitric acid required less energy and resulted in less extensive spontaneous solvent coordination. This experimental trend suggests that, as the ionic radius of the lanthanide ion decreases, a pair of the carbamoylmethylphosphine ligands is able to more completely solvate the bound metal ion thereby weakening the nitrate-metal interaction.

The enantioselective microbial reduction of 6-oxo-8-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-8-azaspiro[4.5]decane-7,9-dione 1 to either of the corresponding (R)- or (S)-6-hydroxy-8-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-8-azaspiro[4.5]decane-7,9-diones 2 and 3 is described.

6-Hydroxybuspirone is an active metabolite of the antianxiety drug buspirone. The (R)- and (S)-enantiomers of 6-hydroxybuspirone were prepared using an enzymatic resolution process. l -Amino acid acylase from Aspergillus melleus (Amano Acylase 30000) was used to hydrolyze racemic 6-acetoxybuspirone to (S)-6-hydroxybuspirone in 95% ee after 45% conversion. The remaining (R)-6-acetoxybuspirone with 88% ee was converted to (R)-6-hydroxybuspirone by acid hydrolysis. The ee of both enantiomers could be improved to 99% by crystallization as a metastable polymorph. (S)-6-Hydroxybuspirone was also obtained in 88% ee and 14.5% yield by hydroxylation of buspirone using Streptomyces antibioticus ATCC 14890.

Resolution of (±)- sec -butylamine by Candida antarctica lipase provided a very low enantiomeric excess of the residual amine when either ethyl or vinyl butyrate was used as the acylating agent. The enantiomeric excess was increased by using ethyl esters of long chain fatty acids. The rate of the reaction was increased by using methyl t -butyl ether as a solvent. ( S )- sec -Butylamine of very high enantiomeric excess was obtained by C. antarctica lipase catalyzed acylation with ethyl decanoate in methyl t -butyl ether.

The synthesis of a new series of arylmethyltin chlorides is reported, ArnMeSnCl3−n (Ar = RC6H4, R = H, ethyl, i-propyl, t-butyl; hexyl, octyl). The synthesis involves initial formation of triarylmethyltin compounds, Ar3MeSn, via Grignard techniques followed by HCl–Et2O aryl group cleavage, preferably in a stepwise manner. Preliminary biological activity against Staphylococcus aureus illustrates the importance of the para-alkyl substituents and reinforces that an optimal hydrophobic character is needed for maximum efficacy. Copyright © 2005 John Wiley & Sons, Ltd.

The single-crystal structure of the hydrophobic actinide extractant di(p-tert-butylphenyl)-N,N-di-(iso-butyl)carbamoylmethylphosphine oxide (CMPO, 1) has been determined, as has that of its 1:1 chelate complex with uranyl nitrate (2), its 1:1 monodentate complexes with Ph3SnCl (3) and Me2SnCl2 (4) bonding via the PO group. A 1:1 bidentate complex with Ph2SnCl2 bonding via both PO and CO functionalities (5) was obtained which in solution exhibits a CO Sn bond dissociation to exist as the monodentate isomer coordinating only through the PO group. Copyright © 2005 John Wiley & Sons, Ltd.

The chiral intermediate ( S )-1-(2′-bromo-4′-fluoro phenyl)ethanol 2 was prepared by the enantioselective microbial reduction of 2-bromo-4-fluoro acetophenone 1 . Organisms from genus Candida , Hansenula , Pichia , Rhodotorula , Saccharomyces , Sphingomonas and Baker's yeast reduced 1 to 2 in >90% yield and 99% enantiomeric excess (ee). In an alternative approach, the enantioselective microbial reductions of methyl, ethyl, and tert -butyl 4-(2′-acetyl-5′-fluorophenyl) butanoates 3 , 5 , and 7 , respectively, were demonstrated using strains of Candida and Pichia . Reaction yields of 40–53% and ee's of 90–99% were obtained for the corresponding ( S )-hydroxy esters 4 , 6 , and 8 . The reductase, which catalyzed the enantioselective reduction of ketoesters was purified to homogeneity from cell extracts of Pichia methanolica SC 13825. It was cloned and expressed in Escherichia coli with recombinant cultures used for the enantioselective reduction of keto methyl ester 3 to the corresponding ( S )-hydroxy methyl ester 4 . On a preparative scale, a reaction yield of 98% and an ee of 99% was obtained.

The chiral intermediate (3R)-cis-3-acetyloxy-4-(1,1-dimethylethyl)-2-azetidinone 2 was prepared for the semi-synthesis of the new taxane 5, an orally active anticancer compound. The enantioselective enzymatic hydrolysis of cis-3-acetyloxy-4-(1,1-dimethylethyl)-2-azetidinone 1 to the corresponding undesired (S)-alcohol 3 and unreacted desired 2 was carried out using immobilized lipase PS-30 or BMS lipase. Reaction yields of >48% and enantiomeric excesses of >99% were obtained for the desired 2. Acetoxy β-lactam 2 was converted to hydroxy β-lactam 4 for use in the semisynthesis of 5.

The chiral intermediate (1S,2R)-[3-chloro-2-hydroxy-1-(phenylmethyl)propyl]carbamic acid, 1,1-dimethylethyl ester 2a was prepared for the total synthesis of the HIV protease inhibitor Atazanavir. The diastereoselective reduction of (1S)-[3-chloro-2-oxo-1-(phenylmethyl)propyl] carbamic acid, 1,1-dimethyl-ethyl ester 1 was carried out using microbial cultures among, which Rhodococcus, Brevibacterium, and Hansenula strains reduced 1 to 2a. Three strains of Rhodococcus gave >90% yield. A diastereomeric purity of >98% and enantiomeric excess of >99.3% were obtained for alcohol 2a.

The chiral ester ethyl (2 R )-hydroxy-2-(1′,2′,3′,4′-tetrahydro-1′,1′,4′,4′-tetramethyl-6′-naphthalenyl) acetate 2 and the corresponding acid 4 were prepared as intermediates in the synthesis of the retinoic acid receptor gamma-specific agonist ( R )-3-fluoro-4-[[hydroxy(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)acetyl]amino]benzoic acid 7 . Enantioselective reduction of ethyl 2-oxo-2-(1′,2′,3′,4′-tetrahydro-1′,1′,4′,4′-tetramethyl-6′naphthalenyl)acetate 1 to alcohol 2 was carried out using Aureobasidium pullulans SC 13849 in 98% yield and with an enantiomeric excess (e.e.) of 96%. Among microorganisms screened for the reduction of 2-oxo-2-(1′,2′,3′,4′-tetrahydro-1′,1′,4′,4′-tetramethyl-6′-naphthalenyl)acetic acid 3 to hydroxy acid 4 , Candida maltosa SC 16112 and two strains of Candida utilis (SC 13983, SC 13984) gave reaction yields of >53% with e.e.s of >96%.

Phenylpyruvate decarboxylase from Achromobacter eurydice was used to catalyse the asymmetric acyloin condensation of phenylpyruvate 1 with various aldehydes 2 to produce optically active acyloins PhCH2COCH(OH)R 3. The specific activity of the phenylpyruvate decarboxylase enzyme was increased by a factor of 332 after its purification. The molecular weight of the purified enzyme was shown to be 150 kDa by gel filtration chromatography, while SDS gel electrophoresis showed two sub-units with molecular weights of 90 and 40 kDa. The acyloin condensation yield decreased with increasing chain length for straight chain aliphatic aldehydes from 76% for acetaldehyde to 24% for valeraldehyde. The e.e.s of the acyloin products were 87–98%. Low yields of acyloin products were obtained with chloroacetaldehyde (13%) and glycoaldehyde (16%). Indole-3-pyruvate was a substrate of the enzyme and provided acyloin condensation product 3-hydroxy-1-(3-indolyl)-2-butanone 5 with acetaldehyde in 19% yield, while benzoylformate was not a substrate for the enzyme.

The study of electrical conductivity, density and coefficient of thermal expansion (CTE) of Na2O:K2O:B2O3:SiO2:BaO glass samples with addition of cerium oxide has been carried out. It has been observed that the addition of cerium oxide affects the electrical conductivity, density and CTE. The results have been explained on the basis of the variation in number of bridging oxygens (BOs) and non-bridging oxygens (NBOs) present in the glass. In general, the glass with more NBOs has a weak network which exhibits higher electrical conductivity. The weakening of the network has been supported by the observed decrease in density and increase in CTE for the glasses.

Cells obtained from growth of Achromobacter eurydice , Pseudomonas aromatica and Pseudomonas putida on l -phenylalanine containing medium catalyzed the enzymatic acyloin condensation of phenylpyruvic acid 1 and acetaldehyde 2 by phenylpyruvate decarboxylase to produce 3-hydroxy-1-phenyl-2-butanone 3 . The acyloin condensation by Achromobacter eurydice and P. aromatica was stereoselective, providing the 3 R enantiomer 3a with enantiomeric excess (ee) of 95% and 84%, respectively. A partially purified enzyme was prepared from the cell free extract of Achromobacter eurydice. The acyloin product 3a was obtained in 45% yield with an ee of 91% by using this partially purified preparation of phenylpyruvate decarboxylase.

Deracemization of racemic 1,2-diol, (RS)-1-{2′,3′-dihydrobenzo[b]furan-4′-yl}-ethane-1,2-diol (1), by stereoinversion by several microorganisms belonging to the genera Candida and Pichia provided the corresponding chiral (S)-diol, (S)-1-{2′,3′-dihydrobenzo[b]furan-4′-yl}-ethane-1,2-diol (2). (S)-Diol 2 was obtained in yields of 60–70% with 90–100% enantiomeric excess.

Among various microbial cultures evaluated, Rhodotorula glutinis SC 16293 and Aspergillus niger SC 16311 catalyzed the stereospecific hydrolysis of the racemic epoxide, RS -1-{2′,3′-dihydrobenzo[ b ]furan-4′-yl}-1,2-oxirane, 1 to the corresponding R -diol, R -1-{2′,3′-dihydrobenzo[ b ]furan-4′-yl}-ethane-1,2-diol, 3 . The S -epoxide, S -1-{2′,3′-dihydrobenzo[ b ]furan-4′-yl}-1,2-oxirane, 2 remained unreacted in the reaction mixture. A reaction yield of 45–50% (theoretical maximum yield is 50%) and an enantiomeric excess (ee) of >95% were obtained for unreacted S -epoxide 2 using each culture. Addition of 10% methyl tert -butyl ether to an aqueous reaction mixture during hydrolysis by R. glutinis improved the ee of the unreacted S -epoxide 2 to >99% (yield 48%) and that of the R -diol 3 to 79%. Unlike R. glutinis , hydrolysis of racemic epoxide 1 in the presence of 10% methyl tert -butyl ether by A. niger showed an adverse effect and gave S -epoxide 2 in 54% yield and 49% ee.

The chiral intermediates (S)-3,4-dihydro-1,2(2H)-pyridinedicarboxylic acid, 1-(phenylmethyl)ester [BMS 202665-01] and (S)-3,4-dihydro-1,2(2H)-pyridinedicarboxylic acid, 1,1-dimethylethyl ester [BMS 264406-01] were prepared by oxidation of Nα-carbobenzoxy- l -lysine (Nα-CBZ- l -lysine) and Nα-t-butoxycarbonyl- l -lysine (Nα-t-BOC- l -lysine), respectively, by cell suspensions of Rhodotorula graminis SC 16005.

A dimolybdenum derivative of decamethylpentasilacycloheptyne (1) was synthesized by direct reaction of the heptyne with Mo2(CO)4(η5-C5H5)2. 1 crystallized in the space group P 1 , a=9.386(2), b=9.866(3), c=20.178(4) A, α=92.17(2), β=97.17(2), γ=115.71(2)°. The acetylenic bond is lengthened from 1.213 A in the free ligand to 1.359(4) A and all the Si–Si bond lengths in 1 are significantly lengthened upon complexation. This is due to relaxation of the ring strain as evidenced by the Si–C–C bond angles in 1 of 132.7 and 140.9° compared to 159.2 and 162.6° in the uncomplexed ring. 29Si-NMR data exhibit significant downfield chemical shifts upon complexation for the Si atoms adjacent to the triple bond, with moderate upfield shifts for the other Si atoms. The related cycloheptyne·Mo2(CO)4(η5-C5H5)2 (2) was synthesized by the reaction of cyclohepteno-1,2,3-selenadiazole with Mo2(CO)4(η5-C5H5)2. 2 crystallized in the space group C21/c, a=30.396(10), b=8.9093(3), c=16.156(4) A, β=115.39(2)°. The acetylenic bond in 2 is 1.345 A, compared with a calculated value (ab initio 3-21 G*) of 1.190 A for the free cycloheptyne.

The chiral intermediate (1S,2R) [3-chloro-2-hydroxy-1-(phenylmethyl)propyl] carbamic acid, 1,1-dimethylethyl ester 2a was prepared for the total synthesis of an HIV protease inhibitor, BMS-186318. The stereoselective reduction of (1S) [3-chloro-2-oxo-1-(phenylmethyl)propyl] carbamic acid, 1,1-dimethyl-ethyl ester 1 was carried out using microbial cultures among which Streptomyces nodosus SC 13149 efficiently reduced 1 to 2a . A reaction yield of 80% was obtained. The optical purity of 99.8% and the diastereomeric purity of 99% were obtained for chiral alcohol 2a .

Chiral intermediate (−)-7-[ N , N ′-Bis(benzyloxycarbonyl)- N -(guanidinoheptanoyl)]-α-acetoxyglycine 2 was prepared for the total synthesis of a (−)-15 deoxyspergualin, an antitumor antibiotic and immunosuppressive agent. The stereoselective acetylation of racemic 7-[ N , N ′-Bis(benzyloxycarbonyl)- N -(guanidinoheptanoyl)]-α-hydroxyglycine 1 was carried out in methyl ethyl ketone (MEK) using lipase from Pseudomonas sp. (lipase AK). Vinyl acetate was used as an acylating agent. A reaction yield of 48% (theoretical max 50%) and an optical purity of 98% were obtained for S-(−)-acetate 2 . The unreacted alcohol (+)- 1 was obtained in 41% yield and 98.5% optical purity.

The chiral intermediate (S) [1-(acetoxyl)-4-(3-phenyl)butyl]phosphonic acid, diethyl ester 2 was prepared for the total synthesis of a squalene synthase inhibitor, BMS-188494. The stereoselective acetylation of racemic [1-(hydroxy)-4-(3-phenyl)butyl] phosphonic acid, diethyl ester 1 was carried out in toluene using lipase from Geotrichum candidum. Isopropenyl acetate was used as an acylating agent. A reaction yield of 38% and an optical purity of 95% were obtained for chiral 2.

A transition metal-substituted silylacetylene [( η 5 -C 5 H 5 )Fe(CO) 2 SiMe 2 C] 2 , [FpMe 2 SiC] 2 ( I ) was synthesized and characterized spectroscopically and structurally. I crystallized in the monoclinic space group P 2 1 n , a = 13.011(3) A b = 12.912(3) A , c = 13.175(5) A , β = 94.95(2) . The acetylene linkage is reactive toward Co 2 (CO) 8 to form I . Co 2 (CO) 6 ( II ) which was also characterized spectroscopically and by single crystal X-ray diffraction. II crystallized in the orthorhombic space group Pbca, a = 17.64(2) A , b = 14.225(10) A , c = 24.49(2) A .

The chiral intermediate diol (3 S ,4 R )-trans-3,4-dihydro-3,4-dihydroxy-2,2-dimethyl-2 H -1-benzopyran-6-carbonitrile 2 . was prepared for the total synthesis of a potassium channel opener drug candidate. The stereoselective acetylation of racemic 1 was carried out with various lipases among which the lipases from Candida cylindraceae and Pseudomonas cepacia catalyzed the acetylation of the undesired enantiomer of racemic 1 to yield monoacetylated product and unreacted desired (+)-trans diol 2 . A reaction yield of >40% and an optical purity >90% were obtained using each lipase.

α-(3-Chloropropyl)-4-fluorobenzenemethanol, a possible intermediate for synthesis of a potential anti-psychotic agent α-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol (BMS 181100), was resolved by acetylation using isopropenyl acetate and lipase PS-30 in heptane. S -alcohol was obtained in 42% yield with >99% optical purity. R -acetate was obtained with 92.6% optical purity by stopping the reaction after 46% conversion. The enzymatically produced acetate was hydrolyzed by lipase PS-30 to give R -alcohol with >99% optical purity after 62–72% conversion. BMS 181100 acetate ester was treated with lipase GC-20 in buffer containing 10% toluene to give the R -alcohol with 97.9% optical purity after 47.6% conversion. The rate and enantioselectivity of hydrolysis by lipase GC-20 were very dependent on the organic solvent. E values ranged from 1 in the absence of organic solvent to >100 with dichloromethane and toluene.

Treatment of ferrocenecarboxaldehyde with base at 0°C, lithium diisopropylamide (LDA) or n-butyllithium, followed by the addition of trimethylsilylcyanide, produced 1-(diisopropylamino)cyanomethylferrocene, FcCH(N{iPr}2(CN) (II) or 1-trimethyl-siloxy-n-pentylferrocene, FcCH(nBu)OSiMe3 (IIIa). The reaction of naphthaldehyde, NpCHO, with LDA/Me3SiCN led to formation of 1-(diisopropylamino)cyanomethylnaphthalene, NpCH{N(iPr)2}(CN) suggesting a general new synthesis for cyanoamines. The reaction of ferrocenecarboxaldehyde with Me3SiCN led to the expected silylether FcCH(CN)OSiMe3 (I). An alternative synthesis of ferrocenylmethylsilylethers, FcCH2OSiR3 (IV), involved the reaction of 1-ferrocenylmethanol with R3SiCl in the presence of pyridine. The basicity of the new silylethers III and IV is reported.

The chiral intermediate (2R,3S)-(−)-N-benzoyl-3-phenyl isoserine ethyl ester 2a , a potential taxol 5 side-chain synthon, was prepared by microbial and enzymatic processes. Taxol 5 is an anticancer compound recently approved by FDA for the treatment of ovarian cancer. The stereoselective reduction of racemic 2-keto-3-(N-benzoylamino)-3-phenylpropionic acid ethyl ester 1 to the corresponding alcohol 2 was carried out using microbial cultures. Among microorganisms evaluated, Hansenula polymorpha SC 13865 and Hansenula fabianii SC 13894 effectively reduced compound 1 to the desired syn diastereomer 2a . Reaction yields of >80% and enantiomeric excesses of >98% were observed for these bioreduction process. About 10–20% of anti diastereomers ( 2c,2d ) were produced during bioreduction.

The compounds of the type [Cp2Ti(RCOCHCOR') (XCOO)] (where Cp = cyclopentad ieny 1; R = R' = CH3 or (CH3)3C; R = CH3, R' = C6H5; × = Cl2CH or Cl3C have been synthesised In aqueous medium by the reactions of [Cp2Ti (RCOCHCOR')]Cl with the sodium salts of dichloroacetic acid or trichloroacetic acid in 1:1 molar ratio. These products have been characterized on the basis of their elemental analyses, electrical conductance, magnetic measurements, and spectroscopic (IR, 1H NMR and electronic) studies.

The first organotin(IV), aluminium(III)-μ-oxoisoprovides of the type [R3SnOA](OiPr)2] (R = Me or Ph) have been made by heating of trimethyl- or triphenyl-tin acetate with aluminium isopropoxide. The reactions of these μ-oxoisopropoxides with benzoylacetone in 1:1 and 1:2 molar ratios yielded the compounds of the type [R3SnOAl(OiPr)(bzac)] and [R3SnOAl(bzac)2] (where R = Me or Ph and bzac = deprotonated benzoylacetone), respectively.

Pentamethyldisilylmethyl derivatives of the transition metals have been synthesized, LMCH2SiMe2SiMe3 [LM = (η5-C5R5) M(CO)n−, M = Fe, W, R = H, Me, n = 2, 3; (η5-C9H7)Fe(CO)2−; (η5-C5H5) 2MCl−, M = Ti,Zr,Hf]. The cyclopentadienylcarbonyl complexes are photochemically labile with respect to rearrangement to LM-SiMe2 CH2SiMe3 and are also subject to base-induced migration to the cyclopentadienyl ring to form (η5-Me3SiCH2SiMe2C5H4) derivatives. The titanium, zirconium and hafnium complexes exhibit neither property; the only compound isolated from the photochemical treatment of these complexes being Me3SiSiMe3. Structural analyses of (η5-C5H5)W(CO)3 CH2SiMe2SiMe3 and its phosphine-substituted rearrangement product, (η5-C5H5)W(CO)2 (PPh3)SiMe2CH2SiMe3, are presented.

Complexes of the general type (η 5 -C 9 H 7 )Fe(CO)(L)Si n (η 5 -C 9 H 7 =η 5 -indenyl; Si n =SiMe 3 , Si 2 Me 5 , 2-Si 3 Me 7 ; L=CO, PPh 3 ) have been synthesized and characterized via X-ray crystallography. Substitution of the CO ligand by PPh 3 results in a significant increase in both the Fe−Si and Si−Si bond distances

The synthesis and structure of the unknown trimethylgermyltriphenylsilane (I, Ph 3 SiGeMe 3 ) is reported. The molecular geometry is compared to that of the isomeric Me 3 SiGePh 3 (II) and the related Ph 3 SiSiMe 3 (III) and (η 5 -C 5 H 5 )Fe(CO) 2 SiMe 2 GePh 3 (IV). The SiGe bond of I is significantly longer than that for II. We suggest that this is due to expansion of Ge bonding orbitals by the relatively electron-donating methyl groups in conjunction with the contraction of the corresponding orbitals of Si due to the electron-withdrawing phenyl groups. The overall result is a better orbital overlap between the Si and Ge atoms for II.

The reaction between Ta(OEt)5 and 1,1,3,3-tetramethyl-1,3-disiloxanediol, (HOSiMe2OSiMe2OH), leads to new siloxy complexes in which the dimeric nature of Ta(OEt)5 is maintained with both bridging ethoxide and disiloxanediolato bridges. With equal amounts of the reagents, two terminal OEt groups are replaced to form [Ta(OEt)2]2(mu-OEt)2(mu-OSiMe2OSiMe2O)2, 1, whereas with an excess of diol, the remaining terminal OEt groups are also replaced but with a trisiloxanediolato unit to form [Ta(OSiMe2OSiMe2OSiMe2O)]2(mu-OEt)2(mu-OSiMe2OSiMe2O)2, 2. Complexes 1 and 2 catalyze the transformation of HOSiMe2OSiMe2OH to polysiloxanes. Thermal treatment of 1 results in the formation of a 1:2 mixture of Ta2O5/SiO2; no new phases are observed. The molecular structures of 1 and 2 are confirmed by X-ray crystallography.

Chemical shift and coupling constant data for a variety of trimethyl-, triethyl-, and triphenyllead complexes of the transition-metal systems Mn(CO) 5 , (η 5 -C 5 H 5 (M(CO) n (M=Fe, Cr, Mo, W), and Co(CO) 4 , and some of their phosphine-substituted derivatives, are reported

The Ph3E−E‘Me3 (E = Si, Ge, Sn; E‘ = Si, Ge, Sn) compounds exhibit two morphotropic steps in the crystalline state: a [E = E‘ = Si; E = Si, E‘ = Ge; E = Ge, E‘ = Si, E = E‘ = Ge (space group P3)] → b [E = Ge, E‘ = Sn; E = Sn, E‘ = Ge (space group Pna21)] → c [E = E‘ = Sn (space group P3)]. Ph3Sn−SnMe3 reverts to group a. Due to the long Sn−Sn bond, it is not isometric, and therefore not isostructural, with the group a compounds; the relaxed relationship is termed as homeostructural.

Trimethyl- and tri ethyllead derivatives (η 5 -C 5 H 5 )M(CO) 3 PbR 3 (M  Cr, Mo, and W) have been synthesized. The trimethyllead derivatives are photochemically, and to a lesser extent, thermally unstable with respect to methyl transfer reactions that yield the corresponding (η 5 -C 5 H 5 )M(CO) 3 CH 3 complex. The related triethyllead complexes behave in a distinctly different fashion exhibiting rearrangements to [(η 5 -C 5 H 5 )M(CO) 3 ] 3 PbEt 2 (M  W, Mo). The reactions of the Cr, Mo, and W complexes with SO 2 yielded the corresponding alkyl sulphinato complexes as did the reaction of the related Fe complex [(η 5 -C 5 H 5 )Fe(CO) 2 PbEt 3 ].

The trivalent ruthenium, rhodium and iridium complexes of dipicolinic acid and its mixed ligand complexes with several nitrogen, oxygen donor molecules, of types: Na[M(dipic) 2 ]·2H 2 O and [M(dipic)(N-O)]· n H 2 O (where M = Ru(III), Rh(III) or Ir(III); dipicH 2 = dipicolinic acid; NOH represents different nitrogen, oxygen donor molecules, viz., picolinic acid, nicotinic acid, isonicotinic acid, glycine, aminophenol, o - or p -aminobenzoic acid), have been synthesized and characterised on the basis of elemental analyses, electrical conductance, magnetic susceptibility measurements and spectral (electronic and infrared) data. The parent dipicolinic acid complexes are found to have a six-coordinate pseudooctahedral structure, whereas for mixed ligand complexes, a polymeric six-coordinate structure has been assigned. Various ligand field and nephelauxetic parameters have also been evaluated.

The reactions of niobium and tantalum pentaethoxides withtrans-cinnamic acid (HCA) and dihydrocinnamic acid (HDCA) were carried out in different stoichiometric ratios. The complexes of the type M(OEt)5−n(CA)n and M(OEt)5−n(DCA)n, (n=1, 2 or 3 and M=Nb or Ta) were obtained.

Bis(cyclopentadienyl)titanium(IV)mercaptoacetamide derivatives of the type Cp2Ti(MA)Cl and Cp2Ti(MA)2 (Cp = cyclopentadienyl and MAH [dbnd] N-(aryl)-2-mercapto-acetamide; aryl = phenyl, o-tolyl, m-tolyl, p-tolyl or α-naphthyl) have been prepared from the reactions of dichlorobis(cyclopentadienyl)titanium(IV) (Cp2TiCl2) with various mercaptoacetamides in tetrahydrofuran (THF) at room temperature in the presence of triethylamine (Et3N). These new mercaptoacetamide derivatives have been characterized by their elemental analyses, electrical conductance, IR, 1H NMR and electronic spectral data.

The synthesis and characterization of the complexes from the reactions of trichloro(cyclopentadienyl)titanium(IV) with 1,5-diarylthiocarbazones (aryl=phenyl,o-tolyl,o-chlorophenyl,p-tolyl,p-chlorophenyl, or 3,5-dimethylphenyl) are reported. They are of the types CpTi(HDz)Cl2 and CpTi(HDz)2Cl (Cp=cyclopentadienyl, HDz−=the mono-anion of a 1,5-diarylthiocarbazone, H2Dz). The compounds are nonelectrolytes in dimethylformamide (DMF). In solid state, the far i.r. spectra of CpTi(HDz)Cl2 indicate the complexes to be dimeric, involving Cl-bridges.

The reactions of niobium and tantalum pentaethoxides and pentachlorides with 2-thiophenecarboxylic acid (HTCA) and 2-thiopheneacetic acid (HTAA) were carried out in different stoichiometric ratios. Complexes of the type M (OEt)5-n (L)n (n = 1–3 and M = Nb or Ta) and MC15-n Ln (n = 1 or 2 and M = Nb or Ta) were obtained and characterised on the basis of elemental analyses and spectral (i.r. and 1H n.m.r.) data.