Buprenorphine hydrochloride, IX-1003, TSN-09(tape), UM-952, NIH-8805, CL-112302, Probuphine, Transtec, Subutex, Temgesic, Buprex, Buprenex-药物合成数据库

【药物名称】Buprenorphine hydrochloride, IX-1003, TSN-09(tape), UM-952, NIH-8805, CL-112302, Probuphine, Transtec, Subutex, Temgesic, Buprex, Buprenex

化学结构式(Chemical Structure):

参考文献No.	277272
标题:	Buprenorphine
作者:	Casta馿r, J.; Paton, D.M.
来源:	Drugs Fut 1977,2(9),570

合成路线图解说明: The hydrogenation of 7-acetyl-6,14-endoetheno-6,7,8,14-tetrahydrothebaine (I) with H2 over Pd/C in acetic acid gives the corresponding endo-ethano derivative (II), which by a Grignard reaction with tertbutyl-magnesium chloride (A) in ether-benzene yields 7alpha-(2-hydroxy-3,3-dimethyl-2-butyl)-6,14-endo-ethano-6,7,8,14-tetrahydrothebaine (III). The reaction of III with BrCN in CH2Cl2 affords 7alpha-(2-hydroxy-3,3-dimethyl-2-butyl)-6,14-endo-ethano-N-cyano-6,7,8,14-tetrahydronorthebaine (IV), which is treated with KOH in ethylene glycol at 170 C to give 7alpha(2-hydroxy-3,3-dimethyl-2-butyl)-6,14-endo-ethano-6,7,8,14-tetrahydronorthebaine (V). This compound is treated first with cyclopropylcarbonyl chloride (B) in CH2Cl2 containing triethylamine, followed by a reduction with LiAlH4 in refluxing THF yielding N-cyclopropylmethyl-7alpha-(2-hydroxy-3,3-dimethyl-2-butyl)-6,14-endo-ethano-6,7,8,14-tetrahydro-northebaine (VI). Finally, (VI) is demethylated with KOH in diethylene glycol at 210-220 C.

参考文献No.	701104
标题:	Thebaine and Oripavine derivatives
作者:	Bentley, K.W.
来源:	CH 558362; DE 1620206; FR 6395M; GB 1136214

合成路线图解说明: The hydrogenation of 7-acetyl-6,14-endoetheno-6,7,8,14-tetrahydrothebaine (I) with H2 over Pd/C in acetic acid gives the corresponding endo-ethano derivative (II), which by a Grignard reaction with tertbutyl-magnesium chloride (A) in ether-benzene yields 7alpha-(2-hydroxy-3,3-dimethyl-2-butyl)-6,14-endo-ethano-6,7,8,14-tetrahydrothebaine (III). The reaction of III with BrCN in CH2Cl2 affords 7alpha-(2-hydroxy-3,3-dimethyl-2-butyl)-6,14-endo-ethano-N-cyano-6,7,8,14-tetrahydronorthebaine (IV), which is treated with KOH in ethylene glycol at 170 C to give 7alpha(2-hydroxy-3,3-dimethyl-2-butyl)-6,14-endo-ethano-6,7,8,14-tetrahydronorthebaine (V). This compound is treated first with cyclopropylcarbonyl chloride (B) in CH2Cl2 containing triethylamine, followed by a reduction with LiAlH4 in refluxing THF yielding N-cyclopropylmethyl-7alpha-(2-hydroxy-3,3-dimethyl-2-butyl)-6,14-endo-ethano-6,7,8,14-tetrahydro-northebaine (VI). Finally, (VI) is demethylated with KOH in diethylene glycol at 210-220 C.