Kozaburo Nishiyama

Radical-based deoxygenation of aliphatic alcohols via thioxocarbamate derivatives

Abstract N-Phenylthioxocarbamates, obtained from the reaction of alcohols with phenyl isothiocyanate in the presence of NaH, were reduced with various silanes such as triethylsilane, triphenylsilane, and tris(trimethylsilyl)silane, as well as tributylstannane under radical conditions to give deoxygenated products of the corresponding alcohols in excellent yields. The reaction was applicable to not only simple aliphatic alcohols but also sugars and nucleosides. Regio- and stereoselective deuteration using deuteriosilanes and deuteriostannane was also examined under the similar conditions.

Determination of peptide φ angles in solids by relayed anisotropy correlation NMR

A solid state NMR method is presented for determination of a backbone dihedral angle phi in peptides, being based on the previously reported method, relayed anisotropy correlation (RACO) NMR [Y. Ishii et al., Chem. Phys. Lett. 256 (1996) 133]. In the present method, the 15N-1H and the 13C-1H dipolar tensors in the 1H-15N-13C-1H system are two-dimensionally (2D) correlated via polarization transfer from 15N to 13C under magic angle spinning (MAS). This method was applied to N-acetyl[1,2-13C,15N]D,L-valine, and the H-C-N-H dihedral angle was determined to be 154.0 +/- 1.4 degrees or 206.0 +/- 1.4 degrees, the former agreeing with the X-ray value of 154 +/- 5 degrees.

Synthesis of L-threo- and L-erythro-[1-13C, 2,3-2H2]amino acids: novel probes for conformational analysis of peptide side chains

An efficient and convenient route for the preparation of L-threo- and L-erythro-[1-l3C, 2,3-2H2]amino acids 5 as probes for the conformational analysis of peptide side chains by NMR spectroscopy is described. Stereoselective incorporation of deuterium into the α,β-positions of amino acid 5 was accomplished by catalytic deuteriation of dehydroamino acid derivatives 1 and 2 followed by a combination of enzymic optical resolution and the racemization at the 2-position. Using the doubly labelled amino acids, it was possible to obtain vicinal coupling constants between carbonyl carbon and prochiral β-protons, J(13C1–1Hβ1) and J(13C1–1Hβ2), through 13C NMR spectroscopy alone. We also demonstrate the determination of the fractional populations of rotamers in respect of the Cα–Cβ bond of the amino acids using the measured coupling constants.

Asymmetric synthesis of l-proline regio- and stereoselectively labelled with deuterium

Abstract A synthesis of l -proline where all of the ring methylenes are stereoselectively labelled with deuterium is described. A catalytic deuteration of protected 3,4-dehydro- l -proline using transition metal catalyst followed by RuO 4 -oxidation gave a [3,4-D 2 ]pyroglutamic acid derivative. A syn -selective deuteration of the aminal derived from the pyroglutamate with Et 3 SiD–BF 3 ·OEt 2 furnished (2 S ,3 S ,4 R ,5 S )-[3,4,5-D 3 ]proline. The present procedure is also applied to the synthesis of the corresponding (2 S ,3 S ,4 R ,5 R )-isomer.

A concise approach to homochiral 3,4-dihydroxyglutamic acids

Abstract A concise diastereoselective synthesis of 3,4-dihydroxyglutamic acids was investigated. The key reaction in this synthesis is stereoselective cyanation of an optically active N -acyliminium intermediate derived from l - or d -tartaric acid. The stereoselectivity in the cyanation reaction could be controlled by the protective group of the hydroxyl function. Deprotection of the obtained cyanolactam followed by acidic hydrolysis afforded the desired 3,4-dihydroxyglutamic acids. The 3,4-dihydroxyglutamic acids obtained in this synthesis are (2 S ,3 S ,4 R )-, (2 R ,3 S ,4 R )-, (2 S ,3 R ,4 S )-, and (2 R ,3 R ,4 S )-isomers and the three latter compounds are novel derivatives of glutamic acids.

Stereoselective deuterium-labelling of diastereotopic methyl and methylene protons of L-leucine

Abstract An asymmetric synthesis of regio- and stereoselectively deuterium-labelled L-leucine was examined using 4-hydroxy-L-proline as a chiral template. An enol triflate of 4-oxoproline prepared from 4-hydroxyproline was effectively methylated by a Gilman reagent to afford a 4-methyl-3,4-dehydroproline derivative. Then, a catalytic deuteration of the dehydroproline followed by RuO 4 -oxidation gave a deuterated 4-methylpyroglutamic acid derivative that could easily be converted to ( 2S,3S,4R )-leucine-3,4,5,5,5- d 5 via a base-promoted ring opening and a reductive deuteration of the terminal carboxyl moiety. This strategy was also applied to the stereoselective synthesis of ( 2S,3S,4S )-[3,4,5,5,5-D 5 ]leucine.

Stereoselective synthesis of triply isotope-labeled Ser, Cys, and Ala: amino acids for stereoarray isotope labeling technology.

Efficient access to highly enantioselective isotope-labeled serine, cysteine, and alanine for stereoarray isotope labeling (SAIL) is described.

Stereoselective synthesis of (2S,3S,4R,5S)-proline-3,4,5-d3

Abstract A catalytic deuteration of protected 3,4-dehydro-L-proline using RuCl 2 (PPh 3 ) 3 followed by RuO 4 -oxidation gave a 3,4-dideuterated L-pyroglutamic acid derivative which is considered to be a promising precursor for various deuterated amino acids. The present study demonstrates a stereoselective reduction of the amide carbonyl moiety leading to L-proline derivatives in which all of the ring methylenes are stereoselectively labeled with deuterium.

Addition reaction and deoxygenation of alcohols using isothiocyanates and triethylsilane-DTBP

Abstract Alcohols were found to be deoxygenated through treatment with isothiocyanates giving thionocarbamates, followed by reduction with triethylsilane.

Diorganotelluride-catalyzed oxidation of silanes to silanols under atmospheric oxygen.

Diorganotellurides efficiently catalyze the aerobic oxidation of organosilanes under photosensitized conditions to afford the corresponding silanols in excellent yield.