CL-115129, DHV-PGE2

合成路线:The reaction of 4-hydroxy-1-octyne (I) with chlorotrimethylsilane and imidazole in DMF gives 4-trimethylsilyloxy-1-octyne (II),which is converted to 1-iodo-4-trimethylsilyloxy-trans-1-octene (III) by reaction with bis(3-methyl-2-butyl)borane,trimethylamine oxide,NaOH and finally I2.The hydrolysis of (III) with acetic acid in THF affords 1-iodo-4-hydroxy-trans-1-octene (IV),which is oxidized with pyridinium chlorochromate in methylene chloride yielding 1-iodo-4-oxo-trans-1-octene (V).The Grignard condensation of (V) with vinylmagnesium bromide in THF gives 4 hydroxy-4-vinyl-1-iodo-trans-1-octene (VI),which is protected with trimethylsilyl chloride as before yielding 4-trimethylsilyloxy-4-vinyl-1-iodo-trans-1-octene (VII).The reaction of (VII) with tert-butyllithium in ether and then with copper(I)-1-pentyne-tributylphosphine in HMPT affords the copper salt (VIII),which is condensed with 2-(6-trimethylsilyloxycarbonyl)-2-cis-hexenyl)-4-trimethylsilyloxycyclopent-2-en-1-one (IX) in ether-THF giving trimethylsilyl-9-oxo-11 alpha,16-bis(trimethylsilyloxy)-16-vinyl-5-cis-13-trans-prostadienoate (X).Finally,this compound is hydrolyzed with acetic acid in THF water.

参考文献标题:15-Deoxy-16-substituted protanoic acids
文献作者:Pfenning,J.; et al.(American Cyanamid Co.)
参考来源:DE 2837530; ES 472908; FR 2401899; GB 2006186; JP 54046748; JP 7946748


合成路线:The reaction of 4-hydroxy-1-octyne (I) with chlorotrimethylsilane and imidazole in DMF gives 4-trimethylsilyloxy-1-octyne (II),which is converted to 1-iodo-4-trimethylsilyloxy-trans-1-octene (III) by reaction with bis(3-methyl-2-butyl)borane,trimethylamine oxide,NaOH and finally I2.The hydrolysis of (III) with acetic acid in THF affords 1-iodo-4-hydroxy-trans-1-octene (IV),which is oxidized with pyridinium chlorochromate in methylene chloride yielding 1-iodo-4-oxo-trans-1-octene (V).The Grignard condensation of (V) with vinylmagnesium bromide in THF gives 4 hydroxy-4-vinyl-1-iodo-trans-1-octene (VI),which is protected with trimethylsilyl chloride as before yielding 4-trimethylsilyloxy-4-vinyl-1-iodo-trans-1-octene (VII).The reaction of (VII) with tert-butyllithium in ether and then with copper(I)-1-pentyne-tributylphosphine in HMPT affords the copper salt (VIII),which is condensed with 2-(6-trimethylsilyloxycarbonyl)-2-cis-hexenyl)-4-trimethylsilyloxycyclopent-2-en-1-one (IX) in ether-THF giving trimethylsilyl-9-oxo-11 alpha,16-bis(trimethylsilyloxy)-16-vinyl-5-cis-13-trans-prostadienoate (X).Finally,this compound is hydrolyzed with acetic acid in THF water.

参考文献标题:Nouveaux acides 15-d閟oxy-16-hydroprotano飍ues 16-substitu�?dou�?d'activit?pharmaceutiques et leur proc�?de pr閜aration
文献作者:Middlenton,B.F.; Martin,J.W.; Grudzinskas,C.V.; Chen,S.L.(American Cyanamid Co.)
参考来源:DE 2813342; ES 468353; FR 2385696; JP 7939047; US 4131737


合成路线:The reaction of 4-hydroxy-1-octyne (I) with chlorotrimethylsilane and imidazole in DMF gives 4-trimethylsilyloxy-1-octyne (II),which is converted to 1-iodo-4-trimethylsilyloxy-trans-1-octene (III) by reaction with bis(3-methyl-2-butyl)borane,trimethylamine oxide,NaOH and finally I2.The hydrolysis of (III) with acetic acid in THF affords 1-iodo-4-hydroxy-trans-1-octene (IV),which is oxidized with pyridinium chlorochromate in methylene chloride yielding 1-iodo-4-oxo-trans-1-octene (V).The Grignard condensation of (V) with vinylmagnesium bromide in THF gives 4 hydroxy-4-vinyl-1-iodo-trans-1-octene (VI),which is protected with trimethylsilyl chloride as before yielding 4-trimethylsilyloxy-4-vinyl-1-iodo-trans-1-octene (VII).The reaction of (VII) with tert-butyllithium in ether and then with copper(I)-1-pentyne-tributylphosphine in HMPT affords the copper salt (VIII),which is condensed with 2-(6-trimethylsilyloxycarbonyl)-2-cis-hexenyl)-4-trimethylsilyloxycyclopent-2-en-1-one (IX) in ether-THF giving trimethylsilyl-9-oxo-11 alpha,16-bis(trimethylsilyloxy)-16-vinyl-5-cis-13-trans-prostadienoate (X).Finally,this compound is hydrolyzed with acetic acid in THF water.

合成路线:The oxidation of 1-hepten-3-ol (XI) with pyridinium chlorochromate gives 1-hepten-3-one (XIII),which by a Grignard condensation with propargylmagnesium bromide (XIII) is converted to 4-hydroxy-4-vinyl-1-octyne (XIV).The protection of (XIV) with trimethylsilyl chloride and imidazole as before yields 4-trimethylsilyloxy-4-vinyl-1-octyne (XV),which by reaction with tri-n-butylstannane and azobisisobutyronitrile at 125 C affords 1-(tri-n-butylstannyl)-4-vinyl-4-(trimethylsilyloxy)-1-octene (XVI).Finally,this compound,by reaction with butyllithium and copper(I)-1-pentyne tributylphosphine as before yields the copper salt (VIII),which is condensed with 2-(6-trimethylsilyloxycarbonyl)-2-cis-hexenyl)-4-trime-thylsilyloxycyclopent-2-en-1-one (IX) in ether-THF giving trimethylsilyl-9-oxo-11 alpha,16-bis(trimethylsilyloxy)-16-vinyl-5-cis-13-trans-prostadienoate (X).Finally,this compound is hydrolyzed with acetic acid in THF water.

参考文献标题:DHV-PGE2
文献作者:Adaikan,P.G.; Serradell,M.N.; Casta馿r,J.
参考来源:Drugs Fut 1985,10(5),382


合成路线:The oxidation of 1-hepten-3-ol (XII) with pyridinium chlorochromate gives 1-hepten-3-one (XIII),which by a Grignard condensation with propargylmagnesium bromide (XIV) is converted into 4-hydroxy-4-vinyl-1-octyne (XV).The protection of (XV) with trimethylsilyl chloride and imidazole in DMF yields 4-trimethylsilyloxy-4-vinyl-1-octyne (XVI),which by reaction with tri-n-butyl-stannane and azobisisobutyronitrile at 125 C affords 1-(tri-n-butylstannyl)-4-vinyl-4-(trimethylsilyloxy)-1-octene (XVII).Finally,this compound by reaction with butyllithium and copper -1-pentyne-tributylphosphine (C) in HMPT yields the copper salt (VIII),already obtained.

合成路线:The oxidation of 1-hepten-3-ol (XI) with pyridinium chlorochromate gives 1-hepten-3-one (XIII),which by a Grignard condensation with propargylmagnesium bromide (XIII) is converted to 4-hydroxy-4-vinyl-1-octyne (XIV).The protection of (XIV) with trimethylsilyl chloride and imidazole as before yields 4-trimethylsilyloxy-4-vinyl-1-octyne (XV),which by reaction with tri-n-butylstannane and azobisisobutyronitrile at 125 C affords 1-(tri-n-butylstannyl)-4-vinyl-4-(trimethylsilyloxy)-1-octene (XVI).Finally,this compound,by reaction with butyllithium and copper(I)-1-pentyne tributylphosphine as before yields the copper salt (VIII),which is condensed with 2-(6-trimethylsilyloxycarbonyl)-2-cis-hexenyl)-4-trime-thylsilyloxycyclopent-2-en-1-one (IX) in ether-THF giving trimethylsilyl-9-oxo-11 alpha,16-bis(trimethylsilyloxy)-16-vinyl-5-cis-13-trans-prostadienoate (X).Finally,this compound is hydrolyzed with acetic acid in THF water.
参考文献标题:Prostaglandins and congeners.29.(16RS)-Rac-15-deoxy-16-hydroxy-16-vivyl-protaglandin E2,an orally and transdermally active hypotensive agent of prolonged duration
文献作者:Bimbaum,J.E.; Cervoni,P.; Chan,P.S.; Chen,S.L.; Floyd,M.B.; Grudzinkas,C.V.; Weiss,M.J.; Dessy,F.
参考来源:J Med Chem 1982,25(5),492-494