Gemeprost, SC-37681, Ono-802, Cergem, Preglandin, Cervagem

合成路线:The reaction of 3-bromopropionic acid (I) with triphenylphosphine (II) in refluxing acetonitrile gives (2-carboxyethyl)-triphenylphosphonium bromide (III),which by a Wittig reaction with 2-oxa-3-hydroxy-6-syn-(3alpha-tetrahydropyranyloxy-4,4-dimethyl-1-trans-octen-1-yl)-7-anti-tetrahydropyranyloxybicyclo- [3.3.0]cis-octane (IV) (prepared according to reference 2) by means of sodium dimethylsulfinate in DMSO yields 9alpha-hydroxy-11alpha,15alpha-bis(tetrahydropyranyloxy)-16,16-dimethyl-alpha-dinorprosta-5-cis-13-trans-dienoic acid (V).The reduction of (V) with H2 over Pd/C in methanol affords the 13-trans-prostenoic acid (VI),which is methylated with CH2N2 in ether yielding the methyl ester (VII).The reduction of (VII) with diisobutyl aluminum hydride in toluene affords the corresponding aldehyde (VIII),which by a Wittig reaction with triethyl phosphonoacetate (IX) by means of NaH in THF is converted into 9alpha-hydroxy-11alpha,15alpha-bis(tetrahydropyranyloxy)-16,16-dimethylprosta-2-trans-dienoic acid ethyl ester (X).The hydrolysis of the ester (X) with KOH in ethanol-water gives the corresponding acid (XI),which is oxidized with CrO3,MnSO4 and H2SO4 in ether - water yielding the protected ketoacid (XII).The hydrolysis of (XII) with acetic acid-water at 80 C gives 9-oxo-11alpha,15alpha-dihydroxy-16,16-dimethyl-prosta-2-trans-13-trans-dienoic acid (16,16-dimethyl-DELTA2-trans-PGE1) (XIII),which is finally methylated with CH2N2 in ether

参考文献标题:Prostaglandin-analoge
文献作者:Hayashi,M.; Kori,S.; Wakatsuka,H.
参考来源:BE 0850084


合成路线:The reaction of 3-bromopropionic acid (I) with triphenylphosphine (II) in refluxing acetonitrile gives (2-carboxyethyl)-triphenylphosphonium bromide (III),which by a Wittig reaction with 2-oxa-3-hydroxy-6-syn-(3alpha-tetrahydropyranyloxy-4,4-dimethyl-1-trans-octen-1-yl)-7-anti-tetrahydropyranyloxybicyclo- [3.3.0]cis-octane (IV) (prepared according to reference 2) by means of sodium dimethylsulfinate in DMSO yields 9alpha-hydroxy-11alpha,15alpha-bis(tetrahydropyranyloxy)-16,16-dimethyl-alpha-dinorprosta-5-cis-13-trans-dienoic acid (V).The reduction of (V) with H2 over Pd/C in methanol affords the 13-trans-prostenoic acid (VI),which is methylated with CH2N2 in ether yielding the methyl ester (VII).The reduction of (VII) with diisobutyl aluminum hydride in toluene affords the corresponding aldehyde (VIII),which by a Wittig reaction with triethyl phosphonoacetate (IX) by means of NaH in THF is converted into 9alpha-hydroxy-11alpha,15alpha-bis(tetrahydropyranyloxy)-16,16-dimethylprosta-2-trans-dienoic acid ethyl ester (X).The hydrolysis of the ester (X) with KOH in ethanol-water gives the corresponding acid (XI),which is oxidized with CrO3,MnSO4 and H2SO4 in ether - water yielding the protected ketoacid (XII).The hydrolysis of (XII) with acetic acid-water at 80 C gives 9-oxo-11alpha,15alpha-dihydroxy-16,16-dimethyl-prosta-2-trans-13-trans-dienoic acid (16,16-dimethyl-DELTA2-trans-PGE1) (XIII),which is finally methylated with CH2N2 in ether
参考文献标题:Effect of ONO-802 on uterine activity and plasma levels of steroid hormones in japanese monkeys (Macaca Fuscata Fuscata)
文献作者:Oshima,K.
参考来源:Acta Obs Gyn Jpn 1977,29(12),1923


产品链接: CAS No. 64318-79-2››