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Sapropterin dihydrochloride, Dapropterin dihydrochloride, R-THBP, 6R-BH4, SUN-0588, Phenoptin, Biopten, Biobuden, Bipten

(6R)-5,6,7,8-四氢生物蝶呤二盐酸盐 沙丙蝶呤 Chemical Name: (-)-(6R)-2-Amino-6-[(1R,2S)-1,2-dihydroxypropyl]-5,6,7,8-tetrahydro-4(3H)-pteridinone dihydrochloride; 6R-L-erythro-Tetrahydrobiopterin dihydrochloride
CAS No. 69056-38-8, 62989-33-7 (free base)
项目整合开发状态: Launched-1992
项目研究机构: BioMarin (Proprietary), BioMarin (Orphan Drug), Daiichi Suntory Pharma (Orphan Drug), Daiichi Suntory Pharma (Originator), Maruho (Marketer)
合成路线:This compound can be prepared in two related ways:1) The catalytic hydrogenation of biopterin (I) with H2 over PtO2 aqueous K2HPO4 at pH 11.4 or aq.(Et)4NOH at pH 12 yields a solution which is acidified with HCl.After evaporation,the residue is crystallized in ethanol - HCl.2) The acetylation of biopterin (I) with refluxing acetic anhydride gives the triacetyl derivative (II),which is hydrogenated with H2 over PtO2 in trifluoroacetic acid,yielding the (6RS)-mixture of triacetyl derivatives (III).Acetylation of (III) with refluxing acetic anhydride affords the tetracetyl (6RS)-derivative (IV),which by fractional crystallization or column chromatography of the dihydrochloride in methanol gives the desired compound as pure (6R)-isomer.
📌 参考资料/链接:
参考文献标题:Preparation process for (6R)-tetrahydro-l-biopterin
文献作者:Sakai,H.; Kanai,T.(Shiratori; Suntory Ltd.)
参考来源:EP 0191335

📄 详细内容


合成路线:This compound can be prepared in two related ways:1) The catalytic hydrogenation of biopterin (I) with H2 over PtO2 aqueous K2HPO4 at pH 11.4 or aq.(Et)4NOH at pH 12 yields a solution which is acidified with HCl.After evaporation,the residue is crystallized in ethanol - HCl.2) The acetylation of biopterin (I) with refluxing acetic anhydride gives the triacetyl derivative (II),which is hydrogenated with H2 over PtO2 in trifluoroacetic acid,yielding the (6RS)-mixture of triacetyl derivatives (III).Acetylation of (III) with refluxing acetic anhydride affords the tetracetyl (6RS)-derivative (IV),which by fractional crystallization or column chromatography of the dihydrochloride in methanol gives the desired compound as pure (6R)-isomer.

参考文献标题:Method for the preparation of tetrahydro-L-biopterin
文献作者:Tateoka,T.; Ishiguro,M.; Nakatsuka,N.(Suntory Ltd.)
参考来源:JP 1984021685


合成路线:This compound can be prepared in two related ways:1) The catalytic hydrogenation of biopterin (I) with H2 over PtO2 aqueous K2HPO4 at pH 11.4 or aq.(Et)4NOH at pH 12 yields a solution which is acidified with HCl.After evaporation,the residue is crystallized in ethanol - HCl.2) The acetylation of biopterin (I) with refluxing acetic anhydride gives the triacetyl derivative (II),which is hydrogenated with H2 over PtO2 in trifluoroacetic acid,yielding the (6RS)-mixture of triacetyl derivatives (III).Acetylation of (III) with refluxing acetic anhydride affords the tetracetyl (6RS)-derivative (IV),which by fractional crystallization or column chromatography of the dihydrochloride in methanol gives the desired compound as pure (6R)-isomer.

参考文献标题:Sapropterin Dihydrochloride
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1991,16(1),30


合成路线:This compound can be prepared in two related ways:1) The catalytic hydrogenation of biopterin (I) with H2 over PtO2 aqueous K2HPO4 at pH 11.4 or aq.(Et)4NOH at pH 12 yields a solution which is acidified with HCl.After evaporation,the residue is crystallized in ethanol - HCl.2) The acetylation of biopterin (I) with refluxing acetic anhydride gives the triacetyl derivative (II),which is hydrogenated with H2 over PtO2 in trifluoroacetic acid,yielding the (6RS)-mixture of triacetyl derivatives (III).Acetylation of (III) with refluxing acetic anhydride affords the tetracetyl (6RS)-derivative (IV),which by fractional crystallization or column chromatography of the dihydrochloride in methanol gives the desired compound as pure (6R)-isomer.

参考文献标题:Pterin chemistry.72.Separation of the diastereomers (6R)- and (6S)-5,6,7,8-tetrahydro-L-biopterin
文献作者:Viscontini,M.; Bieri,J.H.; Furrer,H.J.
参考来源:Helv Chim Acta 1979,62(8),2577-80


合成路线:This compound can be prepared in two related ways:1) The catalytic hydrogenation of biopterin (I) with H2 over PtO2 aqueous K2HPO4 at pH 11.4 or aq.(Et)4NOH at pH 12 yields a solution which is acidified with HCl.After evaporation,the residue is crystallized in ethanol - HCl.2) The acetylation of biopterin (I) with refluxing acetic anhydride gives the triacetyl derivative (II),which is hydrogenated with H2 over PtO2 in trifluoroacetic acid,yielding the (6RS)-mixture of triacetyl derivatives (III).Acetylation of (III) with refluxing acetic anhydride affords the tetracetyl (6RS)-derivative (IV),which by fractional crystallization or column chromatography of the dihydrochloride in methanol gives the desired compound as pure (6R)-isomer.

参考文献标题:Highly stereoselective procedure for (6R)-tetrahydrobiopterin cofactor
文献作者:Matsuura,S.; Murata,S.; Sugimoto,T.
参考来源:Chem Lett 1984,5(5),735-8


合成路线:This compound can be prepared in two related ways:1) The catalytic hydrogenation of biopterin (I) with H2 over PtO2 aqueous K2HPO4 at pH 11.4 or aq.(Et)4NOH at pH 12 yields a solution which is acidified with HCl.After evaporation,the residue is crystallized in ethanol - HCl.2) The acetylation of biopterin (I) with refluxing acetic anhydride gives the triacetyl derivative (II),which is hydrogenated with H2 over PtO2 in trifluoroacetic acid,yielding the (6RS)-mixture of triacetyl derivatives (III).Acetylation of (III) with refluxing acetic anhydride affords the tetracetyl (6RS)-derivative (IV),which by fractional crystallization or column chromatography of the dihydrochloride in methanol gives the desired compound as pure (6R)-isomer.
参考文献标题:IX.The conformations of (6R)- and (6S)-2-amino-6-[(1'R,2'S)-1',2'-dihydroxypropyl]-5,6,7,8-tetra- hydropteridin-4(3H)-one [L-erythro-5,6,7,8-tetrahydrobiopterin] hydrochlorides and their tetraacetyl derivatives
文献作者:Randles,D.; Taguchi,H.; Whittaker,M.J.Pterins.; Armarego,W.L.F.
参考来源:Aust J Chem 1984,37(2),355-66


产品链接: CAS No. 69056-38-8››

产品链接: CAS No.62989-33-7››