Jun-ichi Kunitomo

Mutagenicity of isoquinoline alkaloids, especially of the aporphine type

The mutagenicity of 44 isoquinoline alkaloids was tested in Salmonella typhimurium TA100 and TA98 in the presence or absence of S9 mix. The alkaloids tested included compounds from the isoquinoline, benzylisoquinoline, bisbenzylisoquinoline, monoterpene isoquinoline, berberine, morphinane, hasubanan, benzo[c]phenanthridine and aporphine groups. Among the alkaloids tested, liriodenine was the most potent mutagen for TA100 and roemerine was the most potent for TA98. A clear structure-mutagenicity relationship was observed in a series of aporphine alkaloids (aporphine, dehydroaporphine, 7-oxoaporphine and 4,5-dioxoaporphine), and 10,11-non-substituted aporphines were suggested to exert their mutagenicity through metabolic activation of the 10,11 positions, possibly as the 10,11-epoxides.

Alkaloids of Nelumbo nucifera

Abstract The alkaloids of leaves of Nelumbo nucifera Gaertn. were examined using combined GLC-MS. The occurrence of four new alkaloids, dehydroroemerine (XII), dehydronuciferine (XI), dehydroanonaine (XIII) and N-methylisococlaurine (III) were revealed, besides the known roemerine (V), nuciferine (VI), anonaine (VII), pronuciferine (IV), N-nornuciferine (VIII), nornuciferine (IX), amepavine (I) and N-methylcoclaurine (II).

Syntheses of 3-acetoacetylaminobenzo[b]furan derivatives having cysteinyl leukotriene 2 receptor antagonistic activity

Novel 3-acetoacetylaminobenzo[b]furan derivatives having a modified triene system at the 3-position were synthesized starting with 3-aminobenzo[b]furans. The enol isomers, 3-[(3-hydroxybut-2-enonyl)amino]benzo[b]furans (), of the 3-acetoacetylaminobenzo[b]furans were obtained as stable isomers owing to formation of a hydrogen bonding between the enol hydroxyl group and the amidocarbonyl group. The planarity of the C-2 substituent through the C-3 side chain suggested the existence of a modified conjugational triene system in the enol compound. Cysteinyl leukotriene 1 and 2 receptor antagonistic activities for these compounds were evaluated. 2-(4-Cyanobenzoyl or ethoxycarbonyl)-3-[(2-cyano-3-hydroxybut-2-enonyl)amino]benzo[b]furans (, ) were moderately active.

Preparation of 3-acetoacetylaminobenzo[b]furan derivatives with cysteinyl leukotriene receptor 2 antagonistic activity

Novel 3-acetoacetylaminobenzo[b]furan derivatives with a modified triene system at the 3-position were prepared through acylation of the 3-aminobenzo[b]furans with 5-methylisoxazole-4-carboxylic acid chloride followed by basic cleavage of the isoxazole ring and several of these compounds showed moderate cysteinyl leukotriene receptor 2 antagonistic activity.

The alkaloids of Stephania sasakii: Structure of five new alkaloids

Abstract Five new alkaloids, dehydrocrebanine, 4,5-dioxodehydrocrebanine, stesakine, dehydrostesakine, bisaknadinine and four known alkaloids, lirodenine, lanuginosine, 1-tetrahydropalmatine, d-isocorydine with a few alkaloids of unknown structure were newly isolated from Stephania sasakii. The structures of the new alkaloids were determined from spectral data and chemical evidence.

Structure and synthesis of menisporphine, a new type of isoquinoline alkaloid

Abstract The structure of an unknown yellow base from Menispermum dauricum DC. (Menispermaceae) was determined to be 5,6,9-trimethoxy-7H-dibenzo[de, h]quinolin-7-one from various spectral data and synthesis, and was named menisporphine. This is a new isoquinoline-type alkaloid having a 7H-dibenzo[de, h]quinolin-7-one skeleton for which the general term “oxoisoaporphine” is proposed.

Synthesis and biological activities of novel furo[2,3,4-jk][2]benzazepin-4(3H)-one derivatives.

A novel seven-membered lactam formation method has been established by intramolecular ring closure reaction of 4-bromo-(E)-3-[(2-alkylvinyl)carbonylamino]benzo[b]furans under Heck coupling conditions. A number of furo[2,3,4-jk][2]benzazepin-4(3H)-ones, tricyclicbenzo[b]furans, have been prepared by this method and evaluated for their leukotriene B(4) (LTB(4)) receptor and poly(ADP-ribose)polymerase-1 (PARP-1) inhibitory activities.

Synthesis of 2-, 4- and 5-(2-alkylcarbamoyl-1-methylvinyl)-7-alkyloxybenzo[b]furans and their leukotriene B4 receptor antagonistic activity

Variable 7-carboxylpropoxy or (1-phenyl)ethoxybenzo[b]furan derivatives with (E)- and (Z)-2-alkylcarbamoyl-1-methylvinyl groups at the 2-, 4-, and 5-positions were prepared to find novel and selective leukotriene B(4) (LTB(4)) receptor antagonists. (E)-2-(2-Diethylcarbamoyl-1-methylvinyl)-7-(1-phenylethoxy)benzo[b]furan (4v) showed selective inhibition of the human BLT(2) receptor (hBLT(2)). On the other hand, (E)-2-acetyl-4-(2-diethylcarbamoyl-1-methylvinyl)-7-(1-phenylethoxy)benzo[b]furan (7c) inhibited both human BLT(1) receptor (hBLT(1)) and hBLT(2). The (E)-2-(2-diethylcarbamoyl-1-methylvinyl) group lay on approximately the same plane as the benzo[b]furan ring, whereas the (E)-4-(2-diethylcarbamoyl-1-methylvinyl) group had a torsion angle (45.7 degrees ) from the benzo[b]furan ring plane. However, the (Z)-(2-alkylcarbamoyl-1-methylvinyl)benzo[b]furans were inactive. The inhibitory activity depended on the conformation of the 2-alkylcarbamoyl-1-methylvinyl groups.

Preparation of 2- and 4-(2-alkylcarbamoyl-1-methylvinyl)-7-alkyloxybenzo[b]furans having potent antagonistic activity against human leukotriene B4 BLT1 and/or BLT2 receptors

(E)-2-Acetyl-4-(2-diethylcarbamoyl-1-methylvinyl)-7-(1-phenylethoxy)benzo[b]furan (4b) with a characteristic conformation and (E)-2-(2-morpholinocarbo-1-methylvinyl)-7-ethoxycarbopropoxybenzo[b]furan ((E)-3b) were prepared and evaluated for their leukotriene B4(LTB4) antagonistic activity. Compound 4b showed potent antagonistic activity against human BLT1 and BLT2 receptors. Compound (E)-3b displayed selective BLT2 receptor antagonistic activity. Both compounds were inactive to cysteinyl LT receptors.

Structure of nandazurine, fromNandina domestica thumb

Strukturaufklärung des grünen Farbstoffs Nandazurin, aus Rinden vonNandina domestica Thumb. extrahiert. Chemische Reaktion und Spektren weisen auf eine Zwitterstruktur hin (Formel Ia↔Ib).