Toshiko Kiguchi

A novel and concise synthesis of aminocyclopentitols and 1-deoxynojirimycin via radical cyclization of oxime ethers

Abstract Tributyltin hydride-induced radical cyclization of the oxime ether 3 derived from D -glucose proceeded smoothly to give two amino alcohols 4 and 5 which were converted into two aminocyclopentitol pentaacetates 8 and 12 and 1-deoxynojirimycin known as glycosidase inhibitors.

Radical Cyclization in Heterocycle Synthesis. Part 9: A Novel Synthesis of Aminocyclitols and Related Compounds via Stannyl Radical Cyclization of Oxime Ethers Derived from Sugars

Abstract Stannyl radical addition–cyclization of oxime ethers derived from d -glucose, d -galactose, and d -xylose proceeded smoothly to afford alkoxyamino alcohols which were effectively converted into two types of glycosidase inhibitors or its candidates such as aminocyclitols, 1-deoxynojirimycin, and 1-deoxygalactostatin via reductive ring-expansion of trans alkoxyamino alcohols.

Photocyclisation of enamides. Part 24. Total synthesis of (±)-isofumigaclavine B and (±)-lysergic acid

Total syntheses of two ergoiine-types of alkaloids, (±)-isofumigaclavine B (14)(for the first time) and methyl (±)-Iysergate (21) and methyl (±)-isolysergate (22), via a route involving reductive photocyclisation of the enamide (2) followed by glycol formation and oxidative cleavage of the dihydrofuran ring, are described.

Total synthesis of (+)-azimic acid, (+)-julifloridine, and proposed structure ofN-methyljulifloridine via cycloaddition of nitrone to a chiral dipolarophile

Abstract A combination of 1, 3-dipolar cycloaddition of Z-nitrones to the chiral dipolarophile and subsequent ring transformation of the resulting adducts to the piperidinols has provided a new practical synthesis of 2, 6-disubstituted 3-piperidinol alkaloids, (+)-azimic acid, (+)-julifloridine, and the proposed structure ofN-methyljulifloridine. Download : Download full-size image

Photocyclisation of enamides. Part 39. General strategy for the synthesis of pseudodistomins: synthesis of triacetates of (±)-tetrahydropseudodistomin and proposed structures of pseudodistomins A and B

A synthetic strategy of pseudodistomin was developed by first synthesizing the (±)-(2a,4β,5β)-5-amino-2(3-hydroxypropyl)piperidin-4-o1 14 as a key intermediate via a route involving the reductive photocyclisation of enamide 5 followed by the introduction of a three-carbon side-chain by application of an α-acylamino photo-induced radical allylation by allyltributyltin replacing a methylsulfanyl group. The key intermediate 14 was then converted into the piperidines 19 and 20, with a dienyl side-chain, which have the structures proposed for pseudodistomins A 1 and B 2. However, direct comparisons with the triacetates of the natural alkaloids have shown that a revision of the proposed structures is required.

Photocyclisation of enamides. Part V. Photocyclisation of αβ-unsaturated anilides

Irradiation of N-methyl- and N-benzyl-cyclohex-1-enecarboxanilide (Ia and b) and N-methyl-3,4-dihydronaphthalene-1-carboxanilide (VIII) with a low pressure mercury lamp afforded a mixture of cis- and trans-photocyclised products [the phenanthridones (II) and (III), and the benzophenanthridinones (IX) and (X), respectively], whose ratios were dependent upon the solvent employed. Equilibration and deuterium incorporation experiments provided important information on the reaction mechanism.

Heterologous enzyme immunoassay for serum androstenediol

A heterologous enzyme immunoassay for serum androstenediol (Adiol: 3beta, 17beta-dihydroxy-androst-5-ene) was established. The combination of anti-Adiol antiserum raised in rabbit against Adiol 7-O-(carboxymethyl)oxime (Adiol 7-CMO) conjugated bovine serum albumin (Adiol 7-CMO-BSA) and Adiol 7-iminomethylcarboxylic acid conjugated alkaline phosphatase was used for the assay. The sensitivity of the heterologous assay system was superior to that of a homologous assay system in which an antibody raised in rabbit against Adiol 7-CMO-BSA and enzyme labeled antigen, Adiol 7-CMO conjugated alkaline phosphatase, were used. The minimal amount of Adiol detected was 0.4 ngml(-1) and the measurable range was from 0. 4 to 150 ngml(-1). Intra-assay coefficients of variation (C.V.) were 8.6% (1.52+/-0.13 ngml(-1), mean+/-S.D., n=10) and 6.7% (13.4+/-0.9 ngml(-1), n=10). Inter-assay C.V. were 12.9% (1.63+/-0.21 ngml(-1), n=8) and 11.5% (12.2+/-1.4 ngml(-1), n=8). A linear relation was observed between the serum sample dilution and the Adiol concentration. For recovery study, authentic Adiol was added to serum sample (original concentration: 1.43 ngml(-1)). The calculated final Adiol concentration was 2.99 ngml(-1). The recovery was 98.6% (n=5). The Adiol concentrations in healthy subjects measured by the proposed assay (male: 1.1+/-0.3 ngml(-1) (mean+/-S.D.), range: 0.7-1. 7 ngml(-1), age: 22-50, n=10; female: 0.6+/-0.4 ngml(-1), range: 0. 2-1.6 ngml(-1), age: 23-48, n=20) were consistent with reported values.

Photocyclisation of enamides. Part 14. Substituent effects in the photocyclisation of N-α,β-unsaturated acylanilides

Irradiation of N-α,β-unsaturated acylanilides [(1a–d and 1i) and (2a–f and 2h)] having various substituents on the benzene ring yielded a mixture of cis- and trans-octahydrophenanthridones (3a–f) and dihydroquinolones (5a, e, and f). The N-alkylanilides [(1e–h) and (2b–d)] having an ortho-electron-attracting group, such as CO2Me, Ac, CN, or CONH2, brought about [1,5] migration of the group to afford the trans-lactams (4a–d) and dihydroquinolones (5b–d), while anilides [(1j), (2g), and (8a–c)] having an ortho-carboxy-group afforded the decarboxylactams [(3a), (5a), (9a–c), and (10b and c)].

Photocyclisation of enamides. Part IV. A new stereoselective synthesis of (±)-crinan

(±)-Crinan (XIII) has been synthesised by Stereoselective photocyclisation of N-(2-allylcyclohex-1-enyl)-N-benzylpiperonylamide (VIIa).

Photocyclization of enamides. 381,2 reductive photocyclization of α-(methylthio)- and α-(arylthio) enamides

Reductive photocyclization of α-(methylthio)enamide (2) gave exclusively six-membered lactams (3) and (4) while the same reaction of α-(arylthio)enamides (6) and (12) was found to afford five-membered lactams (7) and (13) as major products. A novel total synthesis of (±)-polyzonimine (18b) was accomplished by applying the newly found reductive photocyclization of α-(naphthylthio)enamide leading to the formation of five-membered lactams