Katsuo Hatayama

Novel epoxysuccinyl peptides Selective inhibitors of cathepsin B, in vitro

A series of new epoxysuccinyl peptides were designed and synthesized to develop a specific inhibitor of cathepsin B. Of these compounds, N‐(L‐3‐trans‐ethoxycarbonyloxirane‐2‐carbonyl)‐L‐isoleucyl‐L‐proline (compound CA‐030) and N‐(L‐3‐trans‐propylcarbamoyloxirane‐2‐carbonyl)‐L‐isoleucyl‐L‐proline (compound CA‐074) were the most potent and specific inhibitors of cathepsin B in vitro. The carboxyl group of proline and the ethyl ester group or n‐propylamide group in the oxirane ring were necessary, the ethyl ester group or the n‐propylamide group being particularly effective for distinguishing cathepsin B from other cysteine proteinases such as cathepsins L and H, and calpains.

Stereochemistry of the 2-hydroxy-1,2,3,4-tetrahydropyridine intermediate of hantzsch cyclization

Abstract Hantzsch cyclization of cyanoethyl 3-aminocrotonate and (E,Z)-4-dialkoxymethyl-2-benzylidene-acetoacetates (5a,b) afforded 3,4-trans-2-hydr

Synthesis and configurational assignment of methyl 3-nitrooxypropyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate

Enantiomeric (+)- and (–)-methy3-nitrooxypropyl 1,4-dihydro-2,6-dimethyl-4-(3- nitrophenyl) pyridine-3,5-dicarboxylate 1 were synthesized by esterification of the optically active monocarboxylic acids (+)-6 and (–)-6, which are available from racemate (±)-6 by optical resolution using cinchonidine and cinchonine. The absolute configuration of the key intermediates (S)-(+)-6 and (R)-(–)-6, was also unambiguously determined by the comparison with optical active (+)- and (–)-1 derived from (R)-(–)- and (S)-(+)-7 and (+)- and (–)-6, and X-ray crystallographic analysis of bromoethyl ester (R)-(–)-8 prepared from the acid (S)-(+)-7.

Chemistry of Hantzsch cyclization: stereochemistry of the 2-hydroxy-1,2,3,4-tetrahydropyridine intermediate of Hantzsch cyclization. X-Ray molecular structure of diastereoisomers of 5-(2-cyanoethyl) 3-methyl 2-dimethoxymethyl-2-hydroxy-6-methyl-4-(3-nitrophenyl)-1,2,3,4-tetrahydropyridine-3,5-dicarboxylates

Hantzsch cyclization of cyanoethyl 3-aminocrotonate and (E,Z)-4,4-dialkoxy-2-benzylideneacetoacetates 12a–h afforded the corresponding 3,4-trans-2-hydroxy-1,2,3,4-tetrahydropyridines 14a–h with high stereoselectivity. 1H NMR and X-ray analyses of compound 14a established the configuration of 3-H and 4-H as trans and that of 3-H and 2-OH as trans also.