KR830001198A - Method for producing △2-PGF₂ and △2-PGE₂ series prostaglandin derivatives - Google Patents

Abstract

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Description

Method for producing △2-PGF2 and △2-PGE2 series prostaglandin derivatives

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Claims (18)

The following structural formula (XVII) compound the following structural formula (VI) to the one lead and the reaction of R ¹ is methyl to obtain the ester of formula (I) obtained wherein, R ¹ is methyl and protected with R ³ can be removed easily After acid hydrolysis of the ester of structural formula (I), which is a group, to optionally separate the protective group, the ester of structural formula (I) in which R ¹ is methyl is hydrolyzed to obtain a compound of structural formula (I) wherein R ¹ is hydrogen. conversion and R ^1, R ² and R ³ have the same meanings as described below, X ¹ and Y ^1, X ² and Y to a ^divalent optionally reduction, respectively the oxygen in the structural formula (I) compound X ¹ and Y ^1, X ² and Y Structural formula (I) compound wherein ² is differently hydrogen or hydroxy, and then X ¹ , Y ¹ , X ² , Y ² , R ² and R ³ are as described below, and R ¹ is hydrogen Optionally esterified to obtain a structural formula (I) compound where X ¹ , X ² , Y ¹ , Y ² and R ² are as described below and R ¹ is not hydrogen, and the obtained structural formula (I) compound is physiologically non-toxic A method for producing a compound of the following structural formula (I), characterized by optionally converting to one metal or amine salt. T-1 In the above structural formula X ¹ and Y ¹ and X ² and Y ² together are oxygen or each differently hydrogen or hydroxyl R ¹ is a) hydrogen or a linear or branched saturated or unsaturated aliphatic or alicyclic hydrocarbon group having 10 or less carbon atoms, b) Physiologically non-toxic metal ion or NH ₄ ± ion or ammonium ion derived from primary, secondary or tertiary amine R ² is a linear or branched alkyl group having 3 to 7 carbon atoms (wherein a CH ₂ group other than an end group may be substituted with oxygen) or a) the nucleus is halogen, trifluoromethyl and/or an alkyl having 1 to 6 carbon atoms Or 1 to 3 halogen or α- or β-thienyl or furyl that may be substituted with alkoxy, or b) the nucleus is halogen, trifluoromethyl and/or alkyl or alkoxy having 1 to 6 carbon atoms, or 3 to carbon atoms It may be substituted with an α- or β-thienyloxy that may be substituted 1 to 3 times with a cycloalkyl of 7 or a cycloalkoxy group having 3 to 7 carbon atoms, R ³ is hydrogen or a protective group that can be easily separated R ^4, the same or different, are straight-chain alkyl or phenyl having 1 to 4 carbon atoms. By reacting lactol of structural formula (II) with a Grignard compound of structural formula (XI) to obtain an alcohol of structural formula (XII), and oxidizing the alcohol of structural formula (XII) obtained, a ketone of structural formula (XIII) was obtained, and the obtained structural formula (XIII) by selectively oxidizing the double bond at the terminal in the diketone to obtain a diol of the structural formula (XIV), and oxidizing the diol of the obtained structural formula (XIV) to obtain a diketoaldehyde of the structural formula (XV) The diketoaldehyde of the structural formula (XV) is reacted with the ylide of the structural formula (VI) to obtain a compound of the structural formula (XVI), or the protecting group in the compound of the structural formula (XV) is removed by acid hydrolysis to obtain a structure of the structural formula (IX). A hide is obtained and the aldehyde of the structural formula (IX) is reacted with the ylide of the structural formula (VI) to obtain a compound of the structural formula (X), or the protecting group R ³ in the compound of the structural formula (XVI) is removed by acid hydrolysis and the structural formula ( A compound of X) is obtained, and optionally a compound of structural formula (X) is reduced with a metal complex hydride to obtain a compound of structural formula (VII), optionally a compound of structural formula (VII), (X) or (XVI) Hydrolysis to obtain a compound of the structural formula (I) (where R ¹ is hydrogen, X ¹ , Y ¹ , X ² , Y ² , R ² and R ³ are as defined in the structural formula (I)), optionally The compound of (I) (where R ¹ , R ³ are hydrogen, R ² is as defined in the structural formula (I), and X ¹ , Y ¹ and X ² , Y ² together represent oxygen) is a metal complex hydride To obtain a compound of formula (I) (wherein X ¹ , Y ¹ and X ² , Y ² each represent hydrogen or hydroxy differently from each other), optionally a compound of formula (I) (where X ¹ , Y ¹ , Y ² , X ² and R ² are the same as defined in the structural formula (I), and R ¹ represents hydrogen) by esterifying a compound of the structural formula (I) (where X ¹ , X ² , Y ¹ , Y ² and R ² are as defined in the structural formula (I), and R ¹ is not hydrogen) to obtain And, optionally, a compound of the structural formula (I) (where X ¹ , X ² , Y ¹ , X ² and R ² are as defined in the structural formula (I), and R ¹ represents hydrogen) is a physiologically non-toxic metal Or a method for producing a compound of the structural formula (I'), characterized by conversion to an amine salt. T-3 In the above structural formula R ¹ , R ² and R ³ are as defined in the structural formula (I), R ⁴ are the same or different and represent straight-chain C ₁ -C ₄ alkyl or phenyl, Hal stands for chlorine, bromine and iodine. ※ Note: It is disclosed according to the contents of the initial application.