Masanori Utaka

Low-temperature method for enhancement of enantioselectivity in the lipase-catalyzed kinetic resolutions of solketal and some chiral alcohols

Abstract Low-temperature method (−40 °C at best) for enhancement of the enantioselectivity in a lipase-catalyzed transesterification was proved to be widely applicable to primary and secondary alcohols and enabled theoretical prediction of the course of enhancement of the enantioselectivity physicochemically.

Asymmetric reduction of Z-3-chloro-3-alken-2-ones with fermenting baker's yeast

Abstract Using fermenting bakers yeast, ZRCHCClCOCH 3 , (R=C 2 H 5 , n-C 5 H 11 , n-C 8 H 17 ) was reduced initially to (S)-RCH 2 C ★ HClCOCH 3 in 44~84% ee, which was further reduced to RCH 2 C ★ HCl C ★ HOHCH 3 in >;98% ee with the syn(2S,3S)/anti(2S,3R) ratios of 2.6~18.3.

SIGNIFICANT EFFECT OF ACYL GROUPS ON ENANTIOSELECTIVITY IN LIPASE-CATALYZED TRANSESTERIFICATIONS

Abstract The effect of the acyl group of acylating agents on the enantioselectivity in the lipase-catalyzed transesterifications of racemic 2-[( N , N -dimethylcarbamoyl)methyl]-3-cyclopenten-1-ol in diisopropyl ether was found to be significant. The enantioselectivity was enhanced markedly by changing the acylating agent from vinyl acetate to vinyl butyrate, and dropped substantially with longer acyl donors. Other acyl donors were also examined.

Me3SiCl-NaI-CH3CN as an efficient and practical reducing agent for benzylic alcohols

Abstract Secondary and tertiary benzylic alcohols are reduced conveniently tothe corresponding aryl alkanes by using Me 3 SiCl-NaI-CH 3 CN reagent in hexane. The reaction was successfully applied to a short step synthesis of (±)-ar-turmerone.

Transition-state models are useful for versatile biocatalysts: kinetics and thermodynamics of enantioselective acylations of secondary alcohols catalyzed by lipase and subtilisin

Abstract Lipases and subtilisins are versatile enzymes capable of showing high enantioselectivity and broad substrate specificity simultaneously. The transition-state models previously proposed to rationalize this important feature were intensively examined from kinetic and thermodynamic viewpoints. Kinetic measurements reaffirmed that chiral discrimination originates from the transition state and that the enantioselectivity results from the reduced activity of the enzymes for the slower-reacting enantiomer, but not from the enhanced activity for the faster-reacting enantiomer relative to a reference alcohol, cyclopentanol. The larger substituent of the slower-reacting enantiomers interacts repulsively with the protein in the transition state, and even the larger substituent of the faster-reacting enantiomers interacts unfavorably to some degree with the protein. A number of thermodynamic parameters, ΔΔ H ‡ and ΔΔ S ‡ , for the subtilisin-catalyzed acylations of secondary alcohols were determined. A linear compensation effect was found between the ΔΔ H ‡ and ΔΔ S ‡ values. As the ΔΔ H ‡ value becomes negatively large, the ΔΔ S ‡ value also becomes negatively large. This observation is explained in terms of the transition-state model. Because the widely accepted concepts such as the lock-and-key mechanism and the induced-fit mechanism cannot account for the peculiar behavior of these enzymes toward unnatural substrates, a new category, the non-lock-and-key mechanism, has been proposed.

A facile synthesis of optically pure L-armentomycin and its D-isomer.Highly enantioselective reduction of the CC double bond of methyl (E)- and (Z)-2,4,4-trichloro-2-butenoate by using baker's yeast

Optically pure L-armentomycin [(S)-2-amino-4,4-dichlorobutanoic acid] and its D-isomer [(R)-2-amino-4,4-dichlorobutanoic acid] were prepared by using methyl (E)- and (Z)-2,4,4-trichloro-2-butenoate as key intermediate, which were reduced with bakers yeast to (R)- and (S)-2,4,4-trichlorobutanoate in 84~92 and 97~98% ee, respectively, in 60~65% yields.

A practical synthesis of chiral 3-chloro-2-hydroxyalkanoates and 2,3-epoxyalcohols

Abstract Asymmetric reduction of 3-chloro-2-oxoalkanoates with bakers yeast gave optically active 3-chloro-2-hydroxyalkanoates with ≥95% e.e. in most cases, which were converted to optically active 2,3-epoxyalcohols with ≥78.0% e.e.

Lipase-catalyzed kinetic resolution of 2-acyloxy-2-(pentafluorophenyl)acetonitrile

The lipase-catalyzed kinetic resolution of (±)-2-acyloxy-2-(pentafluorophenyl)acetonitrile (±)- 1 gave optically active cyanohydrin (S)- 2 and its antipodal ester (R)- 1 ( E = 211), the former of which was transformed (TBSOTf, DMAP) into its TBS-ether (S)- 3 , a new fluorinated chiral building block, and into naproxen ester 4 for X-ray analysis to determine the absolute configuration.

Lipase-catalyzed kinetic resolution of large secondary alcohols having tetraphenylporphyrin

Abstract Large secondary alcohols, 5-[4-(1-hydroxyethyl)phenyl]-10,15,20-triphenylporphyrin ( 1a ) and the zinc complex 1b , designed on the basis of the transition-state model recently proposed by us, were subjected to the lipase-catalyzed transesterifications. The alcohols were resolved using lipases from Pseudomonas cepacia (lipase PS), Candida antarctica (CHIRAZYME L-2), Rhizomucor miehei (CHIRAZYME L-9), and Pseudomonas aeruginosa (lipase LIP) with high enantioselectivities ( E > 100).

Synthesis and CD spectrum of chiral porphyrin dimer

Abstract Chiral porphyrin dimer 1 was synthesized. The UV-vis spectrum of 1 was almost identical with that of the corresponding monomer 2 . The circular dichroism induced in the Soret region of 1 was very strong and of the split type due to the chiral exction coupling.