methyl (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-4-hexenoate -Drug Synthesis Database

【结构式】

【分子编号】39958

【品名】methyl (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-4-hexenoate

【CA登记号】

【分子式】C₁₈H₂₂O₆

【分子量】334.36908

【元素组成】C 64.66% H 6.63% O 28.71%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XXX)

The reaction of (XXVI) with HI and red P in acetic acid gives 4-methyl-5,7-dihydroxyphthalide (XXVII), which is condensed with methyl 6-bromo-4-methyl-4-hexenoate (XXVIII) by means of Ag2O in dioxane yielding the methyl ester (XXIX). The monomethylation of (XXIX) with diazomethane in benzene affords the methyl ester of mycophenolic acid (XXX), which is finally hydrolyzed with aqueous NaOH.

参考文献中间体

合成目标

【1】 Castaner, J.; Hillier, K.; Mycophenolic acid. Drugs Fut 1978, 3, 8, 594.
【2】 Canonica, L.; et al.; Total synthesis of mycophenolic acid. Tetrahedron Lett 1971, 28, 2691-92.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXVI)	39954	5,7-dimethoxy-4-methyl-2-benzofuran-1(3H)-one	C₁₁H₁₂O₄	详情	详情
(XXVII)	39955	5,7-dihydroxy-4-methyl-2-benzofuran-1(3H)-one	C₉H₈O₄	详情	详情
(XXVIII)	39956	methyl (E)-6-bromo-4-methyl-4-hexenoate	C₈H₁₃BrO₂	详情	详情
(XXIX)	39957	methyl (E)-6-(4,6-dihydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-4-hexenoate	C₁₇H₂₀O₆	详情	详情
(XXX)	39958	methyl (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-4-hexenoate	C₁₈H₂₂O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XII)

The cyclization of the 3-oxoglutarate (I) with the alkynal (II) gives the benzoate derivative (III), which is treated with CH3I and NaH to yield the dimethoxy benzoate (IV). The reduction o the formyl group of (IV) by means of NaBH4 affords the hydroxymethyl derivative (V), which is treated with MsCl and TEA to provide the mesylate (VI). The reduction of the mesylate group of (VI) by means of NaBH4 gives the methyl derivative (VII), which is cyclized by means of K2CO3 to yield the isobenzofuranone (VIII). The ozonolysis of the dimethylvinyl group of (VIII) affords the aldehyde (IX), which is oxidized with CrO3 to provide the carboxylic acid (X). The reaction of (X) with diazomethane gives the corresponding methyl ester (XI), which selectively demethylates with BCl3 in CH2Cl2 to yield mycophenolic acid methyl ester (XII). Finally, this compound is hydrolyzed with LiOH to provide the target carboxylic acid.

参考文献中间体

合成目标

【1】 Covarrubias-Zuniga, A.; Gonzalez-Lucas, A.; Dominguez, M.M.; Total synthesis of mycophenolic acid. Tetrahedron 2003, 59, 11, 1989.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	64481	dimethyl 2-[(2E)-3,7-dimethyl-2,6-octadienyl]-3-oxopentanedioate	C₁₇H₂₆O₅	详情	详情
(II)	64482	4-oxo-2-butynyl pivalate	C₉H₁₂O₃	详情	详情
(III)	64483	methyl 3-[(2E)-3,7-dimethyl-2,6-octadienyl]-6-{[(2,2-dimethylpropanoyl)oxy]methyl}-5-formyl-2,4-dihydroxybenzoate	C₂₅H₃₄O₇	详情	详情
(IV)	64484	methyl 3-[(2E)-3,7-dimethyl-2,6-octadienyl]-6-{[(2,2-dimethylpropanoyl)oxy]methyl}-5-formyl-2,4-dimethoxybenzoate	C₂₇H₃₈O₇	详情	详情
(V)	64485	methyl 3-[(2E)-3,7-dimethyl-2,6-octadienyl]-6-{[(2,2-dimethylpropanoyl)oxy]methyl}-5-(hydroxymethyl)-2,4-dimethoxybenzoate	C₂₇H₄₀O₇	详情	详情
(VI)	64486	methyl 3-[(2E)-3,7-dimethyl-2,6-octadienyl]-6-{[(2,2-dimethylpropanoyl)oxy]methyl}-2,4-dimethoxy-5-{[(methylsulfonyl)oxy]methyl}benzoate	C₂₈H₄₂O₉S	详情	详情
(VII)	64487	methyl 3-[(2E)-3,7-dimethyl-2,6-octadienyl]-6-{[(2,2-dimethylpropanoyl)oxy]methyl}-2,4-dimethoxy-5-methylbenzoate	C₂₇H₄₀O₆	详情	详情
(VIII)	64488	6-[(2E)-3,7-dimethyl-2,6-octadienyl]-5,7-dimethoxy-4-methyl-2-benzofuran-1(3H)-one	C₂₁H₂₈O₄	详情	详情
(IX)	64489	(E)-6-(4,6-dimethoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-4-hexenal	C₁₈H₂₂O₅	详情	详情
(X)	64490	(E)-6-(4,6-dimethoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-4-hexenoic acid	C₁₈H₂₂O₆	详情	详情
(XI)	64491	methyl (E)-6-(4,6-dimethoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-4-hexenoate	C₁₉H₂₄O₆	详情	详情
(XII)	39958	methyl (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-4-hexenoate	C₁₈H₂₂O₆	详情	详情

Extended Information