Teijin Limited

Takeshi Toru

Seizi Kurozumi

Toshio Tanaka

Makiko Kobayashi

Sachio Ishimoto

Shuzi Miura

Kiyoshi Bannai

Takeo Oba

Noriaki Okamura

Tatsuyuki Naruchi

Kenzo Watanabe

Akira Ohtsu

Sadakazu Matsubara

Atsuo Hazato

Yoshinobu Hashimoto

Keiji Komoriya

Kenzo Wantanabe

Fukuyoshi Kamimoto

Shuji Miura

Novel 5- or 7-monohalogenated or 5,7-dihalogenated .sup.6 -PGI.sub.1 and 5- or 7-monohalogenated or dihalogenated PGI.sub.2 (except 5-monofluorinated PGI.sub.2). The novel halogenated prostacyclins are useful for controlling vascular actions and also in organ transplantation, extra-corporeal circulation and the like. The present invention also provides processes for preparing the novel halogenated prostacyclins.

Halogenated prostacyclins pharmaceutical use thereof and hydroxy

A novel compound selected from the group consisting of 7-(or 6- or 4-)thiaprostaglandin E.sub.1 derivatives of the formula (I). ##STR1## wherein A represents --CH.sub.2 -- or ##STR2## in which n is 0, 1 or 2, provided that only one A cut of three is ##STR3## R.sup.1 -R.sup.7 and G are as defined in the specification, the 15-epimers of said thiaprostaglandin E.sub.1 derivatives, the enatiomers of said thiaprostaglandin E.sub.1 derivatives or their 15-epimers, and mixtures of these compounds. A 7-thiaprostaglandin E.sub.1 derivative and/or its optical isomer may be prepared by reacting a 2-organo-2-cyclopentenone (II) with an organic copper-lithium compound (III) to effect conjugation reaction. A 6-thiaprostaglandin E.sub.1 derivative and/or its optical isomer may be prepared by subjecting an .alpha.,.beta.-unsaturated ketone (IV) and a thiol (V) to the Michael addition reaction. And, 4-thiaprostaglandin derivative and/or its optical isomer may also be prepared by the Michael addition reaction from a 2-allyl substituted cyclopentanone (VI) and a thiol (VIII). Some compounds ((I)-1) amongst the compounds of the formula (I) and/or their optical isomer are useful for controlling vascular actions such as angina pectoris, vasodilation etc.

Thiaprostaglandin E.sub.1 derivatives, process for production thereof,

A compound selected from thiazolo[3,2-a]pyrimidines or their enolate derivatives represented by the following general formula ##STR1## wherein R.sup.1 and R.sup.2 are identical or different, and each represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 3 to 10 carbon atoms, a substituted or unsubstituted phenyl group, a substituted or unsubstituted cycloaliphatic group having 3 to 8 carbon atoms, a substituted or unsubstituted phenylalkyl group or a substituted or unsubstituted acyl group having 2 to 7 carbon atoms, provided that R.sup.1 and R.sup.2 are not simultaneously hydrogen atoms or substituted or unsubstituted acyl groups having 2 to 7 carbon atoms; and R.sup.1 and R.sup.2, when taken together, may form, with the nitrogen atom to which they are bonded, a 5- or 6-membered ring which may further contain one or more hetero atoms; and acid addition salts of these compounds. The thiazolo[3,2-a]pyrimidines may be prepared by a process comprising (a) reacting a malonic acid derivative of the following general formula ##STR2## wherein R.sup.1 and R.sup.2 are as defined with regard to formula (I), and R.sup.4 and R.sup.5 are identical or different and each represents an alkyl group having 1 to 6 carbon atoms, with 2-aminothiazoline under heat, if desired in the presence of an inert organic solvent, to induce cyclocondensation, or (b) performing said condensation reaction in the presence of an alkali metal alkoxide, if desired in the presence of an inert organic solvent, and neutralizing the resulting enolate with an acid; and if desired, reacting the reaction product of (a) or (b) with an acid. The present invention provides also several processes for preparing enolate derivatives thereof. The thiazolo[3,2-a]pyrimidines, their enolate derivatives and acid addition compounds thereof are useful for regulating the immune function of a warm-blooded animal.

Thiazolo[3,2-a]pyrimidines, derivatives thereof, processes for

Organothiocyclopentanes of the formula ##STR1## wherein E represents &gt;C.dbd.O or ##STR2## in which Z' represents a hydrogen atom, a hydroxyl group or a protected hydroxyl group; X represents --S--, --CH.sub.2 --, --CH.dbd.;  represents a single or double bond; R' represents a monovalent or divalent organic group containing 1 to 25 carbon atoms; R represents a monovalent organic group containing 1 to 25 carbon atoms; Z represents a hydrogen atom, a hydroxyl group or a protected hydroxyl group; and when both E and Z represent a hydroxyl group or a protected hydroxyl group, X represents --S--. Also, 2-organothio-2-cyclopentenones of the formula ##STR3## wherein R and Z are as defined above. The compounds of formula (I) are prepared by reacting 2,3-epoxy-cyclopentanone or its derivatives with mercaptans in the presence of basic compounds. The compounds of formula (II) are prepared by reacting the compounds of formula (I) with mercaptans or organocopper-lithium compounds, and optionally reducing the resulting products, and optionally protecting the hydroxyl group at their cyclopentane ring. The compounds of formula (I) have an action of inhibiting ulcer formation, and are useful intermediates for the compounds of formula (II). The compounds of formula (II) are monothia- or dithia-prostanoic acid derivatives, and exhibit various superior pharmacological actions.

2-Organothio-2-cyclopentenones, organothio-cyclopentanes derived

1,3-Dicarbonyl compounds useful as medicines, agricultural chemicals, perfumes, and their intermediates are prepared by reacting a specific .alpha.,.beta.-unsaturated carbonyl compound with a specific organic copper lithium compound in the presence of an aprotic inert organic solvent, and then reacting the reaction product with an organic carboxylic acid halide or anhydride. In particular, novel 2-acyl-3-substituted cyclopentan-1-ones and 2-acyl-3-substituted cyclohexan-1-ones having important physiological activities are provided.

1,3-Dicarbonyl compounds

Novel optically active compounds of 4-protected hydroxy-cyclopent-2-en-1-ones of the formula ##STR1## wherein R is a splittable protective group for an alcoholic hydroxyl group, and a process for preparing the 4-protected hydroxycyclopent-2-en-1-ones by oxidizing monohydroxy-protected derivatives of cyclopent-1-ene-3,5-diol expressed by the following formula ##STR2## wherein R is the same as defined above. Optically active 4-hydroxycyclopent-2-en-1-one which is an optically active isomer of the compound of formula (2); or optically active cyclopent-1-en-3,5-diol (R-isomer) and a novel diacyl derivative of the diol, a novel monoacylmonosilyl-derivative of the diol and a novel monoacylmonotetrahydropyranol-derivative of the diol, which are intermediates for the protective derivative of formula (1). Processes are also provided for preparing the protective derivatives of formula (1) by converting these intermediates by esterification, hydrolysis, enzymatic processes, etc. The optically active compounds of formula (2) are useful as precursors for the preparation of prostaglandin or its analogues.

Process for the preparation of 4-hydroxycyclopent-2-en-1-one derivatives

A process for preparing cyclopent-2-en-1-one derivatives of the formula ##STR1## wherein R.sub.1 is a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group, and

Process for preparing cyclopent-2-en-1-one derivatives

2-Acyl-3-substituted cyclopentan-1-ones and process for their preparation

New optically active cyclopentene-diol and the mono- or diacyl esters thereof and a process for converting a diacyl ester of cyclopent-1-en-3,5-diol to its monoacyl ester and/or its diol which comprises subjecting a diacyl ester of cyclopent-1-en-3,5-diol containing at least one of the optically active or inactive diacyl ester of trans-cyclopent-1-en-3,5-diol (trans-isomer) and diacyl esters of cis-cyclopent-1-en-3,5-diol (cis-isomer), to the action of a microorganism or enzyme having at least a selectivity in its rates of hydrolyzing the acyloxy group (R) configuration and the acyloxy group (S) configuration of said diacyl ester. These new compounds are valuable as starting materials for the preparation of prostaglandin or its analogues.

New cyclopentene-diols and new acyl esters thereof and process for their

A process for the preparation of 1,4-diacetoxycyclopent-2-ene, which comprises contacting a solution of 1,4-dibromocyclopent-2-ene in an inert organic solvent which is slightly soluble or insoluble in water, with an aqueous solution or suspension of at least one metal salt of acetic acid which is at least partially water-soluble, in the presence of a cationic surface-active compound.

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Hino, Japan

Takeshi Toru