Tohru Horiguchi

Synthesis and biological evaluation of 4-deacetoxy-1,7-dideoxy azetidine paclitaxel analogues.

Three novel 4-deacetoxy-1,7-dideoxy azetidine paclitaxel analogues were synthesized through a convenient route that employed hydroboration-amination and intramolecular S(N)2-type substitution reaction from a natural taxoid taxinine. All analogues have been tested for cytotoxicity against three human tumor cell lines. None of them showed remarkable cytotoxicity compared to paclitaxel against tested tumor cell lines.

Synthesis and biological evaluation of novel 9-functional heterocyclic coupled 7-deoxy-9-Dihydropaclitaxel analogue

Novel 9-functional heterocyclic coupled 7-deoxy-9-dihydropaclitaxel analogues 17 and 22-24 synthesized from a natural taxoid 5-cinnamoyltriacetyltaxicin-I (3) and their biological evaluation in tubulin assembly activity and cytotoxicity in vitro against several human tumor cell lines are first presented. The biologically tested results show that 17, 22 and 23 are inactive in tubulin assembly assay and have no more remarkable cytotoxicities against human tumor cell lines SK-OV3, WIDR and MCF-7, though 22 and 23 exhibit more potent cytotoxicity against human liver cancer and human esophagus cancer cell lines (BEL-7402 and ECa-109) than paclitaxel.

Three new taxane diterpenoids from the seeds of Taxus yunnanensis Cheng et L. K. Fu and T. cuspidata Sieb et Zucc

Abstract Chemical examination of the seeds of the Chinese yew, Taxus yunnanensis Cheng et L. K. Fu and Japanese yew, T. cuspidata Sieb et Zucc resulted in the isolation of three new and rare rearranged abeo taxane type of diterpenoids in addition to several known compounds. The structures of the new taxoids have been established as 9α, 13 α -diacetoxy-11(15→1) abeo taxa-4(20), 11-diene-5α, 10β, 15-triol ( 1 ), 9α, 9 α , 13 α -diacetoxy-10β-benzoyloxy-5α-(3′-dimethyl-amino-3′-phenyl)-propionyloxy-11(15→1) abeo taxa-4(20), 11-diene-15-ol ( 2 ), and 2 α ,7 β ,13 α -triacetoxy-10β-hydroxy-5α-(3′-dimethylamino-3′-phenyl)-propionyloxy-2(3→20)- abeo -taxa-9-one ( 3 ) by a study of their spectral data.

High Stereoselectivity in One-Pot Intramolecular Cycloadditions of Olefinic Silyl Nitronates

Intramolecular silyl nitronate olefin cycloaddition starting from nitro olefins 1 and leading to substituted tetrahydrofuran rings fused to isoxazolines 5 has been achieved in a one-pot protocol involving Michael addition, silylation, cycloaddition, and desilylation steps. The results show that unlike nitrile oxides, silyl nitronates undergo highly stereoselective intramolecular cycloadditions to produce functionalized heterocyclic rings.

Isolation and structure elucidation of a new 11(15->1)-abeotaxane from the Chinese yew, Taxus mairei.

Abstract A new 11(15→1)-abeotaxane diterpenoid (1) along with 11 known taxoids were isolated from the bark of the Chinese yew, Taxus mairei, and the structure was established as 9-deacetyl-9-benzoyl-10-debenzoyl-5-cinnamoyltaxchinin A on the basis of 1D and 2D NMR data.

Highly regio- and stereospecific hydroxylation of C-1 position of 2-deacetoxytaxinine J derivative with DMDO

Abstract A simple chemical oxidation of 2-deacetoxytaxinine J derivative 3 using an excess of dimethyldioxirane (DMDO) results in a highly regio- and stereospecific hydroxylation of the C-1 position to afford the 1β-hydroxy α-4(20)-epoxide 6 and 1β-hydroxy β-4(20)-epoxide 7 . A plausible mechanism of this reaction via ‘insertion’ is proposed.

A Novel Rearranged Taxoid from Needles of the Japanese Yew, Taxus cuspidata Sieb. et Zucc.

Eleven taxoids were isolated from needles of the Japanese yew, Taxus cuspidata Sieb. et Zucc., one of them being a new compound whose structure was established as 5α-cinnamoyl-9α,10β,13α-triacetoxy-11(15→1)abeotaxa-4(20),11-dien-15-ol (7-deactoxytaxuspine J) on the basis of a spectroscopic analysis. Its relative stereochemistry is proposed from the results of a NOESY experiment.

The Synthesis and Biological Activity of 9- and 2′-cAMP 7-Deoxypaclitaxel Analogues from 5-Cinnamoyltriacetyltaxicin-I

Abstract The synthesis and biological activity of new 7-deoxypaclitaxel analogues 3 and 4 in which the hydroxy group at C-2′ of the side-chain, C-9 and C-10 in the B-ring are substituted by cAMP and benozoyloxy group respectively are presented. These derivatives have been first synthesized from a natural taxoid 5-cinnamoyltriacetyltaxicin-I 5 and tested in vitro for cytotoxicity against three human tumor cell lines. The biologically tested results indicate 3 having more potent cytotoxicity and 4 having a remarkably reduced cytotoxicity as well as 33 having no much effect on cytotoxicity against all human tumor cell lines tested in comparison to that of paclitaxel.

Synthesis and antitumor activity of 2-(m-substituted-benzoyl)baccatin III analogs from taxinine

2-m-Azidobenzoyl and 2-m-chlorobenzoyl baccatin III analogs were prepared from taxinine, a major component in Japanese yew leaves. In this study, a novel acetyl migration from 13- to 4-hydroxyl group was observed. The antitumor activity of these compounds was evaluated.

(iPrO)3TiCl-induced reactions of α- and β-4(20)-epoxy-5-hydroxytriacetyltaxicin I

Abstract Chlorotitanium triisopropoxide-induced reaction of α-4(20)-epoxy-5-hydroxytriacetyltaxicin I 2 gave a 4-hydroxymethylene-5-one 4 and a 4-hydroxy-4-chloromethylene 5 , while the corresponding β-4(20)-epoxide 3 gave a 3,8-cyclopropane 6 and a 6/8/5 ring system 7 . Moreover, boron trifluoride-induced reaction of the α-4(20)-epoxide 2 yielded a 6/8/6/7 ring system 8 and an A-ring contracted alcohol derivative 9 . Plausible mechanisms of these reactions are proposed.