Kinetic resolution of poly(ethylene glycol)-supported carbonates by enzymatic hydrolysis

The enzyme-mediated enantioselective hydrolysis of poly(ethylene glycol) (PEG)-supported carbonates is disclosed. The water-soluble carbonates were prepared by immobilization of a racemic secondary alcohol (4-benzyloxy-2-butanol) onto low-molecular weight (av MW 550 and 750) monomethoxy PEG through a carbonate linker. For the screening of the hydrolytic enzymes, the substrate was enantioselectively hydrolyzed by commercially available lipase from porcine pancreas (PPL; Type II, Sigma) to afford the optically active compounds. In this system, the separation of the remaining (S)-substrate and the resulting (R)-alcohol was achieved by an extraction process without a laborious column chromatography. The (S)-carbonate was easily hydrolyzed with K₂CO₃ to afford the corresponding (S)-alcohol. Other MPEG-supported substrates were also hydrolyzed to afford the corresponding optically active alcohols.     

Highly enantioselective preparation of C2-symmetrical diols: microbial hydrolysis of cyclic carbonates

A new type of microbial enantioselective hydrolysis of C₂-symmetrical cyclic carbonates is disclosed. During the screening test of the five-membered substrate (4,5-dimethyl-1,3-dioxolan-2-one 5), Pseudomonas diminuta was selected as the best strain to perform the stereoselective hydrolysis. The reaction of dl-5 with this microorganism in aqueous media containing THF as the co-solvent afforded (S,S)-5 and (R,R)-butanediol 1 in excellent yields. It was found that the ring size did not affect the reactivity and enantioselectivity although the enzyme had a high substrate specificity for the side chain. A six-membered cyclic carbonate, dl-4,6-dimethyl-1,3-dioxan-2-one 6, was smoothly hydrolyzed with higher enantioselectivity to afford the optically active (S,S)-6 and (R,R)-2,4-pentanediol 2.     

Kinetic resolution of d,l-1,2-diols catalyzed by amine-phosphinite bifunctional organocatalysis derived from quinidine

Racemic C₂-symmetric 1,2-diols were kinetically resolved by the acylation reaction catalyzed by the phosphinite derivative of quinidine to afford the corresponding monoacylated product with good to high enantioselectivities.     

An improved synthesis of deuterated Schöllkopf’s bis-lactim ether and its use for the asymmetric synthesis of (R)-[α-2H]-phenylalanine methyl esters

Treatment of (S)-3-isopropyl-2,5-dimethoxy-3,6-dihydropyrazine with trifluoroacetic acid in MeOD results in regioselective deuteration at its C₆-position affording its corresponding (S)-[6-²H₂]-isotopomer in excellent yield with no loss of stereochemical integrity at its C₃-stereocentre. The lithium aza-enolate of this deuterated chiral template has been alkylated with a range of substituted benzyl bromides to afford (3S,6R)-[6-²H]-3-isopropyl-6-benzyl-bis-lactim ethers that were hydrolysed to afford their corresponding (R)-[α-²H]-phenylalanine methyl esters as hydrochloride salts in good yield.     

Convenient access to sterically hindered C2 chiral 2,2,5,5-tetraphenyltetrahydrofuran-3,4-diols: intramolecular selective 1,4-cyclocondensation of (2R,3R)- and (2S,3S)-1,1,4,4-tetraphenylbutanetetraols

Sterically hindered C₂ chiral (3R,4R)- and (3S,4S)-2,2,5,5-tetraphenyltetrahydrofuran-3,4-diols have been conveniently prepared in a very high yield via heterogeneous intramolecular selective 1,4-cyclocondensation of (2R,3R)- and (2S,3S)-1,1,4,4-tetraphenylbutanetetraol in concentrated hydrohalic acids, respectively. Preliminary examination of additives for the Barbas–List reaction showed that in certain cases, the hindered C₂ chiral tetrahydrofuran-3,4-diols were better chiral auxiliaries than enantiopure (R)- and (S)-1,1′-bi-2-naphthols.     

Enantioselective Diels–Alder reaction of o-quinodimethanes by utilizing tartaric acid ester as a chiral auxiliary

The asymmetric Diels–Alder reaction of o-quinodimethanes, generated from benzocyclobutenols in situ, with fumaric acid esters was achieved by utilizing diisopropyl (R,R)-tartrate as a chiral auxiliary to afford the corresponding optically active 1,2-cis-substituted 1-hydroxy tetrahydronaphthalene derivatives with enantioselectivities up to 83% ee.     

Asymmetric hydrogenation of (E)-α,β-bis(N-acylamino)acrylates catalyzed by a rhodium complex with trans-chelating chiral diphosphine ligand

The asymmetric hydrogenation of (E)-α,β-bis(N-acylamino)acrylates was promoted by a rhodium complex bearing a trans-chelating chiral diphosphine ligand (R,R)-(S,S)-PrTRAP, providing the corresponding optically active (2S,3R)-2,3-bis(N-acylamino)carboxylates with 79–82% ee. The 2,3-bis(N-acylamino)carboxylates isolated were readily hydrolyzed under acid to afford (2S,3R)-2,3-diaminocarboxylic acids in 95% yield without epimerization.     

Enzyme-mediated enantioselective hydrolysis of poly(ethylene glycol)-supported carbonates

Kinetic resolution of poly(ethylene glycol)(PEG)-supported carbonates by enzymatic hydrolysis is discussed. Water-soluble carbonates are prepared by immobilization of racemic secondary alcohols onto low-molecular weight monomethoxy PEG (MPEG) through a carbonate linker. Porcine pancreas lipase (PPL) enantioselectively catalyzes the hydrolysis of the substrates to give optically active compounds. In this system, the separation of the resulting alcohols and the remaining substrates is achieved by an extraction process without laborious column chromatography. The carbonates are easily hydrolyzed with K₂CO₃ to afford the corresponding alcohols.     

Asymmetric oxidation of 1,2-diols using N-bromosuccinimide in the presence of chiral copper catalyst

Asymmetric oxidation of 1,2-diols using N-bromosuccinimide (NBS) in the presence of copper(II) triflate and (R,R)-Ph-BOX has been exploited. This oxidation was applicable to asymmetric desymmetrization of meso-hydrobenzoin and kinetic resolution of dl-hydrobenzoin and racemic-cycloalkane-cis-1,2-diols to afford optically active α-ketoalcohols with good to high enantiomeric excess.     

Enzyme-mediated enantioselective hydrolysis of soluble polymer-supported carboxylates

The enzyme-mediated enantioselective hydrolysis of water-soluble polymer-supported carboxylates is disclosed. The representative monomethoxy poly(ethylene glycol) (MPEG, av MW 5000)-supported substrate was synthesized by immobilization of (±)-1-phenylethanol onto the modified MPEG (MPEG/NH₂) through an carboxylate linker with a succinate spacer. For the screening of the hydrolytic enzymes, the substrate was enantioselectively hydrolyzed by lipase from Candida antarctica (Novozym 435) in a mixed solvent (hexane/buffer=9/1) at 30 °C to afford the remaining (S)-substrate and the resulting (R)-alcohol (E value>200). The products were easily separated by a simple procedure without any laborious column chromatography. The substrate was hydrolyzed with NaOH in MeOH/H₂O to afford the corresponding (S)-alcohol. We also found that the structure of the spacer between the MPEG moiety and the carboxylate linker strongly affected both the reactivity and enantioselectivity, and the substrate bearing a glutarate spacer gave the best result. Our procedure was applicable for the preparation of several optically active alcohols.     

Asymmetric electrochemical oxidation of 1,2-diols, aminoalcohols, and aminoaldehydes in the presence of chiral copper catalyst

Asymmetric oxidation of 1,2-diols, aminoalcohols, and aminoaldehydes in the presence of copper(II) triflate and (R,R)-Ph-BOX was accomplished by electrochemical method using Br⁻ as a mediator. This oxidation was applicable to kinetic resolution of racemic cis-cycloalkane-1,2-diols, aminoalcohols, and aminoaldehydes to afford optically active compounds with good to high enantioselectivity.     

Palladium(II)-catalyzed 1,4-addition of arylboronic acids to β-arylenals for enantioselective syntheses of 3,3-diarylalkanals: a short synthesis of (+)-(R)-CDP 840

1,4-Addition of arylboronic acid to trans-β-arylenals proceeded smoothly in acetone-water (10/1) at 10-25 °C in the presence of [Pd(S,S-chiraphos)(PhCN)₂](SbF₆)₂ (0.5 mol %), AgX (X = BF₄, SbF₆, 10 mol %) and aqueous 42% HBF₄ to afford optically active 3,3-diarylalkanals with high enantioselectivities in a range of 86-97% ee. The protocol provided a method for short-step synthesis of optically active (+)-(R)-CDP 840.     

C45- und C50-Carotinoide. 4. Mitteilung. Synthese von optisch aktiven cyclischen C20-Bausteinen und von (2R,2′R)-2,2′-Bis(4-hydroxy-3-methyl-2-butenyl)-β,β-carotin ( = C.p. 450)

C₄₅- and C₅₀-Carotenoids: Synthesis of Optically Active Cyclic C₂₀-Building Blocks and of (2R,2′R)-2,2′-Bis(4-hydroxy-3-methyl-2-butenyl)-β,β-carotene ( = C.p. 450) The synthesis of the optically active C₂₀-building blocks (R)- 26 and (R)- 39 and of the optically active cyclic C₅₀-carotenoid C.p. 450 ( 3 ) starting from (?)-β-pinene is reported.     

Enantioselective epoxidation of α,β-enones promoted by (1R,3S,4S)-2-azanorbornyl-3-methanol as an organocatalyst

(1R,3S,4S)-2-Azanorbornyl-3-methanol was synthesized form (R)-1-phenylethylamine and used as a catalyst for the enantioselective epoxidation of α,β-enones to afford the corresponding epoxides in good yields and high enantioselectivities at room temperature.     

Easy separation of optically active products by enzymatic hydrolysis of soluble polymer-supported substrates

The easy separation of optically active compounds from enzymatic kinetic resolution products by simple precipitation using poly(ethylene glycol)(PEG)-supported carbonates is disclosed. The water-soluble substrate was prepared by the immobilization of (±)-1-phenylethanol onto a middle-molecular weight (av M_w 5000) monomethoxy PEG (MPEG) through a carbonate linker. The enantioselective hydrolysis using Lipase from porcine pancreas (PPL; Type II, Sigma) in a mixed solvent (hexane/buffer = 9:1) proceeded to afford the corresponding optically active compounds. In this system, the separation of the products was achieved by a simple procedure without laborious column chromatography. A hydrophobic spacer between the MPEG moiety and the carbonate linker affected both the reactivity and enantioselectivity, and the substrate with a phenylethyl spacer was hydrolyzed with the highest enantioselectivity (E value = 270).     

A novel and efficient method for the catalytic direct oxidative carbonylation of 1,2- and 1,3-diols to 5-membered and 6-membered cyclic carbonates

In the presence of a PdI₂-based catalytic system, 1,2-diols undergo an oxidative carbonylation process to afford 5-membered cyclic carbonates in good to excellent yields (84-94%) and with unprecedented catalytic efficiencies for this kind of reaction (up to ca. 190 mol of product per mol of PdI₂). Under similar conditions, 6-membered cyclic carbonates are obtained for the first time through a direct catalytic oxidative carbonylation of 1,3-diols (66-74% yields).     

C45 und C50-Carotinoide. 6. Mitteilung. Synthese eines optisch aktiven cyclischen C20-Bausteins und von Decaprenoxanthin (= (2R, 6R, 2′R, 6′R)-2,2′-Bis(4-hydroxy-3-methylbut-2-enyl)-ϵ, ϵ-carotin)

C₄₅- and C₅₀-Carotenoids: Synthesis of an Optically Active Cyclic C₂₀-Building Block and of Decaprenoxanthin ( = (2R, 6R, 2′R, 6′R)-2,2′-Bis(4-hydroxy-3-methylbut-2-enyl)-?, ?-carotene) The synthesis of the optically active cyclic C₂₀-building block (R, R) -15 and of the optically active C₅₀-carotenoid (2R, 6R, 2′R, 6′R)-decaprenoxanthin ( 1 ) starting from (-)-β-pinene ((S)- 2 ) is reported.     

Synthesis and Reactions of Optically Active 1,3-Diols

The ‘syn’-1,3-diols 3 , 4 and 5 with a C₇, C₆, and C₅ chain, respectively, were synthesized from methyl hydrogen 3-hydroxyglutarate ( 2 ; Schemes 1 and 2). The latter is available in (R)- and (S)-configuration. Octyl (3R)-4-chloro-3-hydroxybutanoate ( 17 ) is an alternative starting material for the preparation of 5 (Scheme 3.) The epoxide 20 , derived from 5 in a one-pot reaction, is a versatile synthon, which selectively reacts with a great number of nucleophiles (Scheme 4).     

An enzyme-triggered enantio-convergent cascade-reaction

The biocatalytic hydrolysis of the (±)-2,3-disubstituted cis-chloroalkyl epoxides 1a and 2a using resting cells of Rhodococcus sp. did not give the corresponding chloroalkyl vic-diols 1b, and 2b, respectively, but furnished the rearranged products (2R,3R)-1c and (2R,3R)-2c in high e.e. as the sole products via an enzyme-triggered enantio-convergent cascade-reaction.     

Chemo-enzymatic short-step total synthesis of symbioramide

A concise synthesis of symbioramide, a marine-origin ceramide from a common starting material, methyl (±)-trans-2,3-epoxyoctadecanoate, in a convergent manner was achieved. The key step is the direct lipase-catalyzed coupling reaction between methyl (2R,3E)-2-hydroxy-3-octadecenoate and non-protected (±)-erythro-dihydrosphingosine, giving natural (2S,3R,2′R)-symbioramide and its (2R,3S,2′R)-isomer in 38% and 37% yield, respectively. The optically active β,γ-unsaturated α-hydroxyester was prepared by Mg(ClO₄)₂-mediated isomerization of epoxide and the subsequent lipase PS-catalyzed kinetic resolution.