Seiichi Nishi

A practical synthesis of antiviral cyclopropane nucleoside A-5021

Abstract (1′ S ,2′ R )-9-[[1′,2′-bis(hydroxymethyl)cycloprop-1′-yl]methyl]guanine (A-5021, 1 ) was synthesized from optically active cyclopropane lactone 2 by employing: (1) selective reduction of the ester; (2) alkylation of 2-amino-6-chloropurine; and (3) reductive opening of the lactone ring. This route eliminates the protection steps to give 1 in a good yield and is of practical value.

Synthesis of N-acyl-α-amino esters via cobalt-catalyzed carbonylation of N-acyl-α-alkoxyamines

Abstract A variety of N -acyl-α-amino esters were synthesized from N -acylamines through anodic oxidation followed by cobalt-catalyzed carbonylation with high efficiency. By utilizing this method, the highly stereoselective synthesis of trans -6-methylpipecolic acid was also achieved. Some mechanistic aspects of the carbonylation are discussed.

Stereo-Selective Preparation of Teneraic Acid, trans -(2 S ,6 S )-Piperidine-2,6-dicarboxylic Acid, via Anodic Oxidation and Cobalt-Catalyzed Carbonylation

Teneraic acid (piperidine-2,6-dicarboxylic acid) is a naturally occurring imino acid that comprises three stereoisomers due to its two asymmetric centers at C2 and C6. The configuration of natural teneraic acid is reported to correspond to trans-(2S,6S). However, a few studies are focused on the stereospecific synthesis of trans-(2S,6S)-teneraic acid. The present study investigates a convenient synthetic method that includes regiospecific anodic oxidation and stereospecific cobalt-catalyzed carbonylation to obtain trans-(2S,6S)-teneraic acid. Methyl (S)-N-benzoyl-α-methoxypipecolate, the key intermediate that displays a structure that corresponds to an intermediate (N-α-hydroxyalkyl amide) of intramolecular amidocarbonylation, was obtained via an anodic oxidation of methyl (S)-N-benzoylpipecolate. Subsequently, cobalt-catalyzed carbonylation converted the methyl (S)-N-benzoyl-α-methoxypipecolate to trans-(2S,6S)-N-benzoyl-teneraic acid dimethyl ester in good optical purity (>95% enantiomeric excess (ee)) and modest yield (63%). Finally, de-protection occurred via acidic hydrolysis to obtain trans-(2S,6S)-teneraic acid. The stereochemistry of synthesized teneraic acid was confirmed as corresponding to trans-(2S,6S) by comparing its physical properties with those of a cis-meso-isomer and those of a trans-(2S,6S)-isomer that were reported in previous studies.

Enantioselective synthesis of the carbapenem ring system from (S)-proline

Enantioselective synthesis of (+)-PS-5 via stereoselective alkylation of proline derivatives is described.