東郷 秀雄

Various N-methylsaccharins were easily prepared in moderate to good yields by the reaction of N-methyl(o-methyl)arenesulfonamides with (diacetoxyiodo)arene in the presence of iodine under irradiation with a tungsten lamp. The present method is very useful for the direct preparation of saccharins with N-methyl(o-methyl)arenesulfonamides containing various substituents on the aromatic ring.

This mini reveiw deals with the synthesis and their properties of a new type of nucleosides, so-called C-azanucleosides, along with the synthetic method for their related compounds, azafuranopentose. The DNA and RNA have been known to play an important role in the protein synthesis and the life processes. The azanucleosides seem very attractive to scientists as a new class of DNA and RNA subunit compounds.

The development of novel water-soluble organosilane compounds and their application to radical reactions in water medium have been studied. A series of novel organosilane compounds having hydrophilic groups, such as an ether group and a hydroxy group in the side chain to bear hydrophilicity, were synthesized by the reaction of trichlorosilane or tetrachlorosilane and Grignard reagents. The reactivities of these organosilane compounds were studied in the radical reduction of 2-bromoethyl phenyl ether in ethanol in the presence of triethylborane under aerobic conditions. The results showed that diarylsilane was the most effective among them. The radical reduction of alkyl and aryl halides with diarylsilane was applied to a reaction in aqueous media, which gave the corresponding reduction product in good yields. Thus, the present organosilanes are very useful for the reduction of water-soluble substrates, such as halo sugars in water.

Direct coupling reactions of the protected D-ribofuranosyl p-anisyl telluride and 2-deoxy-D-ribofuranosyl p-anisyl telluride with electron-poor heteroaromatics and electron-rich aromatics via anomeric radical, cation, and anion were carried out. (C) 1997 Elsevier Science Ltd.

o-Alkyl- or o-aryl-benzenecarboxylic acids and alcohols containing an aromatic ring are treated with a (diacetoxylodo)arene-iodine system to give the corresponding cyclized products such as phthalide, benzocoumarin and chromane derivatives in moderate to good yields via the corresponding oxygen-centred radicals. For the carboxylic acids, [bis(trifluoroacetoxy)iodo]benzene functions effectively, while (diacetoxyiodo)benzene is effective for the alcohols. Chromane and its derivatives are obtained as iodinated compounds by hypoiodite species derived from (diacetoxyiodo)benzene and iodine.

Trivalent iodine compounds, especially, (diacetoxy) iodoarenes have been used for the formation of 1) oxygen-centered radicals from alcohols, hemi-acetals or carboxylic acids, 2) nitrogen-centered radicals from amine derivatives, and 3) carbon-centered radicals from carboxylic acids or half oxalate esters via decarboxylation. These radicals generated were employed for the Barton type reaction, beta-fragmentation, oxidative addition and substitution reactions, the Hofmann-Loffler-Freytag type reaction and reductive addition reaction. Furthermore, these reactions are successfully used for the functional group transformations and for the preparation of new skeletons.

Trivalent iodine compounds have been used for the generation of 1) alkyl radicals from the corresponding carboxylic acids, 2) alkoxy and aminyl radicals from alcohols and amines, 3) azidyl radical from azide, and 4) aryl cation radicals via the SET pathway. These radicals have been used for substitution, reductive addition, beta-fragmentation and Barton-type reactions. Furthermore, these reactions are successfully used for functional group transformations and for the preparation of new skeletons. The advantages of these systems are simple experimental operation and low toxicity of the reagents.

The photochemically initiated reactions and the atmospherically initiated reactions of alkyl aryl tellurides with electron-deficient heteroaromatic bases in the presence of N-acetoxy-2-thiopyridone and triethylborane, respectively have been investigated. These reactions were applied to the preparation of carbocyclic four-membered C-nucleoside analogs. (C) 1997 John Wiley & Sons, Inc.

The coupling of 2,3,5-tri-O-benzyl-D-ribofuranose with the magnesium, cadmium and zinc salts of typical aromatic heterocycles can afford the corresponding beta-C-nucleosides stereoselectively, Furthermore, the present method can be applied to the synthesis of beta-C-deoxynucleosides having N-containing aromatic heterocycles as base moieties.

Sulfonamides of primary amine bearing an aromatic ring at gamma-position were treated with (diacetoxyiodo)arene and iodine under irradiation conditions with a tungsten lamp to give the corresponding 1,2,3,4-tetrahydroquinoline derivatives in moderate to good yields.

O-Benzylated acyclic sugars are allowed to react with azidotrimethylsilane in the presence of boron trifluoride-diethyl ether to afford the corresponding 1,1-diazido sugars, cyano sugars, and interestingly, 1,1-diazido sugars degradated at the 1-position of carbon.

The coupling reaction of a D-ribofuranosyl fluoride with indoles in the presence of boron trifluoride gives the corresponding C-nucleosides in a stereoselective manner depending upon reaction temperatures and solvents: the beta-anomer is preferred under such conditions as -15 to -40 degrees C in nitroethane while the alpha-anomer is preferred at -78 degrees C in propiononitrile.

Sulfonamides of primary amine bearing an aromatic ring at gamma-position were treated with (diacetoxyiodo)arene and iodine under irradiation conditions with a tungsten lamp to give the corresponding 1,2,3,4-tetrahydroquinoline derivatives in moderate to good yields. The present reaction proceeded under mild and neutral conditions. Copyright (C) 1996 Elsevier Science Ltd

Oxidative cyclization of alcohols containing an aromatic ring with (diacetoxyiodo)benzene and iodine gave the corresponding cyclic ethers via alkoxy radicals in good yields. The present method is very useful for the direct preparation of flavonoid and vitamin E analogues from the alcohols. Copyright (C) 1996 Elsevier Science Ltd

Dimethyl acetylenedicarboxylate, ethyl propiolate, nitro olefins, or 2-nitroalkyl acetates react with thioimidate in the presence of organic bases to give the corresponding pyrroles in moderate-to-good yields.

Oxidative cyclization of o-alkyl- or o-arylaromatic carboxylic acids with [bis(trifluoroacetoxy)iodo]benzene and iodine via aromatic carbonyloxy radicals gave the corresponding lactoncs in good yields.

Dimethyl acetylenedicarboxylate, ethyl propiolate, nitro olefins, or 2-nitroalkyl acetates react with thioimidate in the presence of organic bases to give the corresponding pyrroles in moderate-to-good yields.

The reactivity of [bis(1-adamantylcarbonyloxy)iodo] arenes with 4-methylquinoline (substitution) as a typical heteroaromatic base and phenyl vinyl sulfone (addition) as atypical activated olefin has been studied under thermal and irradiation conditions. The results suggest that electron-withdrawing groups on the aromatic ring in [bis(1-adamantylcarbonyloxy)iodo]arenes are detrimental to reactions. The crystal structures of [bis(1-adamantylcarbonyloxy)iodo]arenes Ib and le are reported.

Thermolysis of perbenzylated D-glucopyranosediyl diazide 1 and D-galactopyranosediyl diazide 4 afforded, respectively, the corresponding 6-oxa-1,5-pentamethylenetetrazoles 2 and 5 via the sugar azido nitrenes, while, photolysis of diazides 1 and 4 gave, respectively, compounds 2 and 5 together with the corresponding byproducts, 10-oxa-1,5-pentamethylenetetrazoles 3 and 6, Similarly, 5-(sugar chain)-substituted tetrazole 9 was obtained by the thermolysis of perbenzylated 1,1-diazido acyclic sugar 8, while compound 9 and 1-(sugar chain)-substituted tetrazole 10 were formed by the photolysis of compound 8. Interestingly, the thermolysis and photolysis of 1,1 -diazido-2,3-di-O-benzyl-D,L-glyceraldehyde 8f gave both the corresponding 9f and 10f.

Seven C-2-deoxy-D-ribonucleosides bearing typical aromatic heterocycles as base moiety are synthesized in good yields by the stereoselective addition of lithium salts of aromatic heterocycles to the silyl-protected 2-deoxy-D-ribose followed by cyclization and deprotection.

The direct coupling reaction of D-ribosyl fluoride with typical pi-excessive aromatic heterocycles stich as furan, thiophene, pyrrole, benzofuran, benzothiophene, and indole and their trimethylsilyl derivatives was performed in the presence of boron trifluoride to afford the corresponding C-nucleosides in moderate to good yields.

Irradiation of [bis(1-adamantanecarboxy)iodo]arenes with a high-pressure mercury lamp in the presence of disulfides gives the corresponding adamantyl sulfides in high yields. This reaction proceeds via the radical decarboxylation of [bis(1-adamantanecarboxy)iodo]arenes followed by S(H)2 reaction of the carbon radical on the disulfide.

Several oxazoles and thiazoles were synthesized easily by the reaction of N-(methylthioalkylidene)glycine ethyl ester with diethyl oxalate, acid halides, and thionesters in the presence of base.

Photolysis of O-acyl derivatives of N-hydroxy-2-thiopyridone. prepared from tetrahydrofuran-2-carboxylic acid. D-ribofuranosylmethanoic acid, land D-ribopyranosylmethanoic acid, gave the corresponding C-nucleoside derivatives in the presence of heteroaromatic compounds via radical pathways. The essential step in this method is a radical coupling reaction of D-ribofuranosyl radical or D-ribopyranosyl radical and some heteroaromatic bases. This isa new method for the preparation of C-nucleosides using sugar carboxylic acids.

New carbocyclic four-membered C-nucleosides have been synthesized from the corresponding carboxylic acids and heteroaromatic compounds by the use of the Barton radical reaction. These carbocyclic nucleosides are analogues of oxetanosyl and cyclobutyl N-nucleosides which exhibit potent antiviral activities. The present synthetic routes provide a method for the preparation of cyclobutyl C-nucleosides.

Alkyl halides were treated with protonated heteroaromatic bases in the presence of 1,1,1,3,3,3-hexamethyl-2,2-bis(trimethylsilyl)trisilane under photochemical conditions to give the corresponding alkylated heteroaromatic bases easily. The alkylation of protonated heteroaromatic bases with 1,1,1,3,3,3-hexamethyl-2-(trimethylsily)trisilane proceeded effectively under photochemical conditions or thermal conditions. The present method is the first report on the alkylation of heteroaromatic bases under non-oxidative conditions.

Transformation of alkyl N-(vinyloxy)benzimidates to alkyloxazoles proceeds through the intermediates: a charge-separated 1,2-oxazetidine derivative and then 1-hydroxy-2-[[methylthio(phenyl)methylene]imino]maleic acid diester, while their photochemical transformation takes place via a concerted [1,3] sigmatropic shift. As the extension of this reaction, the preparation of the precursor proposed for virginiamycin M2 synthesis and the reaction of N-analogs of alkyl N-(vinyloxy)benzimidates are described.

1,1-Diazido-2,3,4,5,6-penta-O-benzyl-D-glucose was refluxed in o-xylene under argon atmosphere to give 5-[(1'R,2'S,3'R-1',2',3',4'-tetrabenzyloxy)butyl]tetrazole in a high yield via an unpreceding rearrangement with one carbon shortening of sugar skeleton. In contrast its photolysis afforded two tetrazoles caused by the rearrangements without one carbon degradation; 5-[(1'S,2'R,3'R,4'R-1',2',3',4',5'-pentabenzyloxy)-pentyl]tetrazole and 1-[1'R,2'S,3'R,4'R-1',2',3',4',5'-pentabenzyloxy)pentyl]tetrazole.

Azomethines (Schiff's bases) derived from alpha,beta-unsaturated alpha-fluoroaldehydes can be deprotonated with lithium diisopropylamide. The resulting ''anions'' or, correctly, 3-fluoro-1-azapentadienyl lithium compounds are conformationally mobile. While eight different coplanar structures are possible, one of them, a zigzag shaped (W) conformation must be largely favored. - Depending on their nature, electrophiles attack the 1-azapentadienyl intermediates at either of the three nodal points: the nitrogen atom, the fluorine bearing alpha-position or the terminal gamma-position. Allyl type alkylating reagents produce a mixture of alpha- and gamma-regioisomers from which the pure components can be separated. Consecutive hydrolysis and reduction provides alpha-fluoroalkenals and alpha-fluoroallyl alcohols.

Some C-ribo-nucleosides having typical aromatic heterocycles as base moiety were synthesized from the stereoselective addition of lithium salt of aromatic heterocycles to the protected D-ribose followed by the stereospecific cyclization under Mitsunobu conditions.

(Diacyloxyiodo)arene was treated with electron-deficient olefins in the presence of hydrogen donor such as 1,4-cyclohexadiene to give the reductive addition products via alkyl radical through the radical decarboxylative pathway in good yields. Moreover, this system was able to generate either alkoxycarbonyl radicals or alkyl radicals with [bis(alkoxyoxalyloxy)iodo]benzene, which was prepared from alcohol, oxalyl chloride, and (diacetoxyiodo)benzene via two steps, depending on reaction conditions. These radicals were also utilized for C-C bond formation with electron-deficient olefins.

Some sugar tetrazoles have been synthesized by the photolysis or the thermolysis of d-glucopyranosylidene diazide of d-galactopyranosylidene diazide. The reaction mechanism is discussed. © 1993.

Some sugar tetrazoles have been synthesized by the photolysis or the thermolysis of D-glucopyranosylidene diazide or D-galactopyranosylidene diazide. The reaction mechanism is discussed.

A 2,3,5-tri-O-benzyl-D-ribose reacts with lithium salts of thiophenes or furans to give the corresponding 2-ribosylthiophenes or furans, which are then treated with p-toluenesulfonic acid, affording 2-ribofuranosylthiophenes or furans (C-nucleosides) in good yield and in a stereoselective manner.

Protonated heteroaromatic bases were easily alkylated via radical pathways using alkyl halides in the presence of tris(trimethylsilyl)silane under photochemical or thermal conditions.

Radicals generated from (diacyloxyiodo)benzene readily added to phenyl vinyl sulfone to give 2-alkylethyl phenyl sulfone in the presence of a hydrogen donor such as 1,4-cyclohexadiene, 1,3-dioxolane, or triethylsilane. Among these donors, 1,4-cyclohexadiene was the most effective.

Facile and general preparative method of C-nucleosides has been achieved via 4 steps starting from 2-deoxy-D-ribose. The essential step in this method is the use of radical coupling reaction of 2-deoxy-D-ribofuranosyl radical derivative and some heteroaromatic bases.

Heteroaromatic bases were alkylated with selenuranes, which were formed by the reaction of diphenylselenoxide and carboxylic anhydrides, under photoirradiation conditions. This reaction was presumed to proceed via a radical pathway accompanying decarboxylation.

Alkyl O-vinylcarbohydroximates, lactoxime O-vinyl ethers, and sugar lactoxime O-vinyl ethers undergo a novel thermal rearrangement to afford the corresponding 2-alkyloxazoles, 2- (omega-hydroxyalkyl)oxazoles, and oxazoles bearing a sugar moiety, respectively. This rearrangement can also occur under photochemical conditions.