Japan Tobacco Inc.

Yuki Gosei Kogyo Co., Ltd.

Fuji Flavor Co., Ltd.

Japan Tabacco Inc.

Japan Tobacco Co.

Yuji Gosei Kogyo Co., Ltd.

Takashi Ebata

Hajime Matsushita

Koshi Koseki

Hiroshi Kawakami

Katsuya Matsumoto

Kazuo Itoh

Yoshitake Naoi

Mikio Ono

Koji Okano

Yasuhiro Kajihara

Junko Tanaka

Hisashi Kodama

Junji Ohki

Nobuhiro Mizutani

Hiromi Kaibara

Hajime Yoshikoshi

Masakazu Okaniwa

Sialic acid derivative and method of manufacturing it

Method of producing cis-whiskey lactone

Method of manufacturing D-allosan

Method of preparing epoxide

Method for preparing 2'-3'-dideoxy-.beta.-nucleosides using

Providing a method of preparing (3R,4R)-3-hydroxy-4-hydroxymethyl-4-butanolide conveniently and selectively from a widely available raw material in a high yield. A carbonyl group of the 2-position of levoglucosenone is reduced to obtain a hydroxyl group of a .beta.-configuration. Then, an iodo-group of an .alpha.-configuration and an acyloxy ion of a .beta.-configuration are introduced regioselectively and stereoselectively to the double bond at the 4-position and the 3-position of the above-mentioned levoglucosenone, respectively, keeping a trans stereochemical relationship. An alkoxide is then formed, by hydrolysis and an oxirane ring of a .beta.-configuration is formed by removing an iodo-group by intramolecular nucleophilic displacement reaction of the alkoxide. After the hydroxyl group of the 2-position is oxidized to convert to a carbonyl group, the oxirane ring is reductively and selectively cleaved, thereby obtaining a chemical compound having no substituent at the 3-position and a hydroxyl group of a .beta.-configuration at the 4-position. Finally a lactone of 5-membered-ring is prepared by subjecting the above-obtained compound to Baeyer-Villigar oxidation.

Method of preparing (3R,4R)-3-hydroxy-4-hydroxymethyl-4-butanolide

method of preparing D-altrose

Method of preparing 3-DPA-lactone

Method for manufacturing 4-substituted-Y-lactone and novel substance

Method of manufacturing 3-DPA-lactone

A method for producing (R,Z)-5-tetradecen-4-olide, comprising the following reaction formulas; ##STR1##

Method for producing (R,Z)-5-tetradecen-4-olide

An acid addition salt of .delta.-aminolevulinic acid is prepared in such a way that tetrahydrofurfurylamine (VI) is reacted with phthalic anhydride under an anhydrous condition to introduce a phthal group which protects amino group of tetrahydrofurfurylamine to give N-tetrahydrofurfuryl phthalimide (III), carbon atoms of the first- and fourth-positions of thus obtained N-tetrahydrofurfurylphthalimide (III) are oxidized at 80.degree. C. using sodium periodate as a oxidizing agent and ruthenium chloride hydrate as a catalyst to yield 5-phthalimidolevulinic acid (II), then the protecting group of 5-phthalimidolevulinic acid (II) is deprotected using an acid to prepare an acid additional salt of .delta.-aminolevulinic acid. The acid additional salt of .delta.-aminolevulinic acid is readily converted by neutralization by an alkali to .delta.-aminolevulinic acid, which is very useful as a precursor of Vitamin B.sub.12, heme and chlorophyll.

Method of preparing an acid additional salt of delta-aminolevulinic acid

The instant invention is drawn to a method for manufacturing 2',3'-dideoxy-2',3'-didehydronucleoside compounds by reacting a ribonucleoside derivative wherein the hydroxyl in the 5'-position of the furanose ring of said ribonucleoside is protected by a silyl protective group, with an acid anhydride such as acetic anhydride in the presence of a catalyst such as hydrous zirconium oxide, and then subjecting the reaction product to decarboxylation. The decarboxylation can be effected by heating the reaction product. This method can be performed in a single step, and requires no reagents which are expensive or chemicals which should be handled with care. Hence, it serves to manufacture 2',3'-dideoxy-2',3'-didehydronucleosides easily at low cost.

Method of manufacturing 2',3'-dideoxy-2',3'-didehydronucleosides

First, levoglucosenone is made to react with methyl lithium in the presence of copper iodide in order to introduce a methyl group into an enone group of levoglucosenone, and to obtain 1,6-anhydro-3,4-dideoxy-4-C-methyl-.beta.-D-erythro-hexopyranose-2-ulose. This methyl compound is oxidized in acetic acid for lactone formation, and (3S,4S)-5-hydroxy-3-methylpentan-4-olide is thus obtained. Further, this lactone is made to react with tosyl chloride in anhydrous pyridine to obtain (3S,4S)-3-methyl-5-tosyloxypentan-4-olide (tosylate). The obtained tosylate is alkylated with n-propyl lithium in the presence of copper iodide to obtain (3S,4R)-3-methyl-4-octanolide. Here, the (3S,4S)-3-methyl-5-tosyloxypentan-4-olide may be treated with potassium carbonate to cleave lactone ring once, thereby obtaining epoxide. After that, the obtained epoxide is alkylated to form lactone ring again to obtain (3S,4R)-3-methyl-4-octanolide.

Method of preparing trans-3,4-disubstituted-.gamma.-lactones

(S)-4-hydroxymethyl-.gamma.-lactone is prepared by oxidizing dihydrolevoglucosenone with a peracid in an organic solvent. (S)-4-hydroxymethyl-.gamma.-lactone is prepared from levoglucosenone. First, levoglucosenone is catalytic hydrogenated, thereby dihydrolevoglucosenone is obtained. Next, dihydrolevoglucosenone thus obtained is oxidized with a peracid in an organic solvent, thereby (S)-4-hydroxymethyl-.gamma.-lactone is obtained. In this manner, (S)-4-hydroxymethyl-.gamma.-lactone can be obtained with high optical purity.

Method of producing (S)-4-hydroxymethyl-.gamma.-lactone

Growing community of inventors

Yokohama, Japan

Takashi Ebata