Toshiko Watanabe

Mild air-oxidation of 1,3-dicarbonyl compounds with cesium salts: Novel α-hydroxylation accompanied by partial hydrolysis of malonate derivatives

Abstract 1,3-Dicarbonyl compounds (1) were efficiently oxygenated at the α-position with cesium salts, such as CsF or Cs2CO3 (0.1 Meq) in DMF at room temperature. Reaction of malonate derivatives (1a, b) with excess amount (2 Meq) of Cs2CO3 gave α-hydroxylmonoester (3) formed by oxygenation and partial hydrolysis, which was decarboxylated to a lactic acid derivative (5).

Fischer indolization of 2-sulfonyloxyphenylhydrazones: A new and practical approach for preparing 7-oxygenated indoles and application to the first synthesis of eudistomidin-A. (Fischer indolization and its related compounds. Part 28)☆☆☆

Abstract An efficient method for synthesis of 7-oxygenated indoles was established by Fischer indolization of the phenylhydrazones ( 10 ) with a sulfonyloxy group at the ortho -position. This method was applied to the first synthesis of the calmodulin antagonist eudistomidin-A ( 2 ).

Total synthesis of 12-methoxydihydrochelerythrine and anti-tumour activity of its quaternary base: toward an efficient synthetic route for 12-alkoxybenzo[c]phenanthridine bases via naphthoquinone monooxime from 2-benzofuranyl-1-tetralone derivative.

A concise total synthesis of 12-methoxydihydrochelerythrine (6), isolated from Bocconia integrifolia, is described. The synthesis features an efficient route to a 12-alkoxybenzo[c]phenanthridine skeleton via naphthoquinone monooxime 11 as a key compound. Starting from 7-methoxy-2-methylbenzo[b]furan (9), 3-aryl-1-tetralone 10 was synthesised, followed by aromatisation to 3-aryl-1-naphthol 17. After oxidative cleavage of the furan ring, basic nitrosation of naphthol 22 gave the naphthoquinone 11. The benzo[c]phenanthridine skeleton was formed by reductive cyclisation of 11. Deoxygenation of the lactam moiety in 23 afforded nor-base 32 and methylation of 32 under reductive conditions gave the target dihydro base 6 (23 steps from benzofuran 9 in 10% overall yield). The corresponding quaternary base 7 showed moderate anti-tumour activity against cancer cell lines; on NCI-H460: IC50 4.5 microM and on MDA-MB-231: IC50 1.2 microM. Introduction of a methoxy group into the 12-position of the benzo[c]phenanthridine skeleton could cause enhanced activity against MDA-MB-231 by comparison of 7 with chelerythrine (35) (IC50 5.3 microM).

Chemical constituents of Aristolochia constricta: antispasmodic effects of its constituents in guinea-pig ileum and isolation of a diterpeno-lignan hybrid.

Twenty constituents were isolated from the n-hexane and chloroform extracts of Aristolochia constricta, a plant whose aerial parts have been used empirically in folk medicine for various purposes. The inhibitory effects of these constituents on smooth muscle contraction in isolated guinea-pig ileum were studied in order to observe their antispasmodic effects. 3,4-Dibenzyldihydrofuran-type lignans [(-)-cubebin, (-)-hinokinin, and (-)-pluviatolide] and a kaurene-type diterpene [(-)-kaur-16-en-19-oic acid] were isolated as active principals. They inhibited electrically induced and acetylcholine-induced contraction in the isolated guinea-pig ileum. In addition, 9- O-[(-)-kaur-15-en-17-oxyl]cubebin was isolated as a new diterpeno-lignan hybrid, although this constituent did not exhibit antispasmodic activity.

Arnottin II, a unique spiro compound composed of a 3, 4-dehydro-1-tetralone and a phthalide skeleton: Is it biosynthetically related to a benzo[c]phenanthridine alkaloid ?

Abstract The structure of arnottin II ( 2 ) was determined to be 3, 4-dehydro-6, 7-methylenedioxy-1-tetralone-2-spiro-3′-(6, 7-dimethoxyphthalide) by its synthesis. The exciton chirality method on the Cotton effects in the CD spectrum revealed the absolute stereochemistry as an R configuration. The biosynthetical relationship of 2 to chelerythrine ( 3 ), a benzo[ c ]phenanthridine alkaloid, is speculated.

Stereoselective total synthesis of (±)-homochelidonine

Abstract (±)-Homochelidonine, a B/C- cis -11-hydroxyhexahydrobenzo[ c ]phenanthridine alkaloid, was stereoselectively synthesized from arnottin II, a non-alkaloidal spirolactonyl tetralone which had been structurally correlated to chelerythrine, a fully aromatized-type alkaloid, by the common use of a 2-benzofuranyl-1-tetralone as a synthetic key intermediate. Thus, a valuable synthetic method accessible to benzo[ c ]phenanthridine alkaloids with different oxidation stages of the basic skeleton could be proposed.

New labdane-type diterpenoids from Croton oblongifolius and their cytotoxic activity

Eight new labdane-type diterpenoids (1-3) and (5-9) and hardwickiic acid (4), a clerodane, were isolated from the stem bark of Croton oblongifolius. Their structures were established to be 3-oxygenated ent-manoyl oxide derivatives with a 8,13-epoxytricyclic ring system and hydroxylabdandienes on the basis of spectroscopic and X-Ray crystallographic analysis. The absolute stereochemistry of the core labdane skeleton was deduced to be (5S,8S,9S,10R,13S) from the X-Ray crystallographic analysis of the p-bromobenzoate of ent-3α-hydroxymanoyl oxide (3) and mutual chemical correlation. Cytotoxicity of these compounds was tested against a panel of human tumor cell lines.

Complexability of o-bisguanidinobenzenes with arsenic and phosphoric acids in solution and solid states, and the potential use of their immobilized derivatives as solid base ligands for metal salts and arsenic acid

The role of o-bisguanidinobenzenes (BGBs) as new Brønsted base ligands for arsenic and phosphoric acids was examined. In solution state, complexation was evaluated by Job’s plot in 1H NMR experiment, indicating a 1:1 complex formation, whereas in solid state crystalline structures of complexes obtained were addressed by X-ray crystallographic analysis and/or solid state 13C NMR experiment, in which 1:2 complexes between the BGB and the acid components were normally formed. Based on these results, Merrifield and Hypogel® resin-anchored BGBs were designed and prepared as the corresponding polymer-supported host ligands. Evaluation of their coordination ability with metal salts (ZnCl2 and CoCl2) and arsenic acid in aqueous media by ICP-MS showed that the latter Hypogel® resin-anchored BGBs acted as effective immobilized base ligands.

Synthesis of linear ethyl 9-methoxy-1H-benz[f]indole-2-carboxylate

This paper describes a synthesis of genuine ethyl 9-methoxy-1H-benz[f]indole-2-carboxylate (6). The genuine synthetic specimen has different physical properties from those of the indole reported as ethyl 9-methoxy-1H-benz[f]indole-2-carboxylate, which was obtained by Fischer indolisation of ethyl pyruvate 2-(1-methoxy-2-naphthylhydrazone)(9) by Goldsmith and Lindwall.Our synthetic method includes the Friedel–Crafts acylation of ethyl pyrrole-2-carboxylate (13) with phthalic anhydride and a new selective N-debenzylation of N-benzylindole derivatives having a methoxy group in their molecule with aluminium chloride in anisole at room temperature.

Conversion of the naturally occurring amide alkaloids into O5 benzo[c]phenanthridinium alkaloids. A new synthetic sequence to antitumour benzo[c]phenanthridine alkaloids

Cyclisation of methyl integriamide (17a) and methyl isoarnottianamide (17b) by the Bischler–Napieralski reaction gave the naturally occurring O5, benzp[c]phenanthridine alkaloids, chelirubine (5a) and chelilutine (5b), respectively; this was extended to give a generally applicable, versatile synthesis of benzo[c]phenanthridine alkaloids from 2-aryl-3,4-dihydronaphthalen-1(2H)-ones (13). Treatment of the tetralones (13) with methylamine and titanium tetrachloride followed by sodium borohydride provided the cis-2-aryl-N-methyl-1,2,3,4-tetrahydro-1-naphthylarmines (14) which were converted into the N-formyl derivatives (15) with freshly prepared chloral in good yields. Dehydrogenation of the resulting formamides (15) with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) gave the fully aromatised amides corresponding to methyl integriamide (17a). Bischler–Napieralski reaction of these amides (17) furnished the desired quaternary benzo[c]phenanthridine alkaloids (5).