Colforsin daropate hydrochloride, Colforsin dapropate hydrochloride, Colforsin daproate hydrochloride, NKH-477, Adehl
NKH 477(达福尔考辛) b-丙氨酸,N,N-二甲基-,(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-5-(乙氧)-3-乙烯基十烷基-10,10b-二羟基-3,4a,7,7,10a-五甲基-1-氧代-1H-石脑松[2,1-b]吡喃-6-伊酯 Chemical Name: 6-O-[3-(Dimethylamino)propionyl]forskolin hydrochloride; (+)-(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-5-Acetoxy-6-[3-(dimethylamino)propionyloxy]-10,10b-dihydroxy-3,7,7,10a-pentamethyl-3-vinyldodecahydro-1H-naphtho[2,1-b]pyran-1-one hydrochloride; 7beta-Acetoxy-6beta-[3-(dimethylamino)propionyloxy]-1alpha,9alpha-dihydroxylabd-14-en-11-one hydrochloride; N,N-Dimethyl-beta-alanine [3R-(3alpha,4abeta,5beta,6beta,6aalpha,10alpha,10abeta,10balpha)]-5-(acetyloxy)-3-ethenyldodecahydro-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-1H-naphtho[2,1-b]pyran-6-yl ester hydrochloride
CAS No. 138605-00-2, 113462-26-3 (free base)
项目整合开发状态: Launched-1999
项目研究机构: Nippon Kayaku (Originator)
合成路线:The silylation of forskolin (I) with tert-butyl-dimethylsilyl chloride and imidazole in DMF gives the protected compound (II),which is deacetylated with aqueous NaOH at room temperature,yielding (III).The acylation of (III) with 3-chloropropionyl chloride in pyridine-dichloromethane affords 1-O-(tert-butyl-dimethylsilyl)-7-O-(3-chloropropionyl)-7-deacetylforskolin (IV),which is treated with dimethylamine in dichloromethane to give the corresponding dimethylamino derivative (V).The desilylation of (V) with trifluoroacetic acid in methanol yields compound (VI),which is submitted to isomerization by means of NaOH in water - acetonitrile,affording 7-deacetyl-6-O-[3-(dimethylamino)propionyl]forskolin (VII).Finally,this compound is acetylated with acetyl chloride and pyridine.
📌 参考资料/链接：
参考文献标题:Novel forskolin derivs
文献作者:Tatee,T.; Takahira,T.; Yamashita,K.; Sakurai,M.; Shiozawa,A.; Narita,K.; Uchida,H.(Nippon Kayaku Co.,Ltd.)
参考来源:EP 0222413; JP 1988010783; JP 1993294955; US 4954642
📄 详细内容
合成路线:The silylation of forskolin (I) with tert-butyl-dimethylsilyl chloride and imidazole in DMF gives the protected compound (II),which is deacetylated with aqueous NaOH at room temperature,yielding (III).The acylation of (III) with 3-chloropropionyl chloride in pyridine-dichloromethane affords 1-O-(tert-butyl-dimethylsilyl)-7-O-(3-chloropropionyl)-7-deacetylforskolin (IV),which is treated with dimethylamine in dichloromethane to give the corresponding dimethylamino derivative (V).The desilylation of (V) with trifluoroacetic acid in methanol yields compound (VI),which is submitted to isomerization by means of NaOH in water - acetonitrile,affording 7-deacetyl-6-O-[3-(dimethylamino)propionyl]forskolin (VII).Finally,this compound is acetylated with acetyl chloride and pyridine.
参考文献标题:Synthesis of water-soluble forskolin derivatives and its cardiovascular activity
文献作者:Izumi,G.; Shiozawa,A.; Sakurai,M.; Narita,A.; Tatee,T.; Yamashita,K.; Narita,K.; Takahira,T.
参考来源:11th Symp Med Chem (Dec 4-5,Tokushima) 1990,Abst P-16
合成路线:The silylation of forskolin (I) with tert-butyl-dimethylsilyl chloride and imidazole in DMF gives the protected compound (II),which is deacetylated with aqueous NaOH at room temperature,yielding (III).The acylation of (III) with 3-chloropropionyl chloride in pyridine-dichloromethane affords 1-O-(tert-butyl-dimethylsilyl)-7-O-(3-chloropropionyl)-7-deacetylforskolin (IV),which is treated with dimethylamine in dichloromethane to give the corresponding dimethylamino derivative (V).The desilylation of (V) with trifluoroacetic acid in methanol yields compound (VI),which is submitted to isomerization by means of NaOH in water - acetonitrile,affording 7-deacetyl-6-O-[3-(dimethylamino)propionyl]forskolin (VII).Finally,this compound is acetylated with acetyl chloride and pyridine.
参考文献标题:NKH-477
文献作者:Castar,J.; Prous,J.
参考来源:Drugs Fut 1993,18(2),134
产品链接: CAS No. 138605-00-2›› 产品链接: CAS No.113462-26-3››