SB-RA-31012011, -Drug Synthesis Database

【结构式】

【药物名称】SB-RA-31012011

【化学名称】3-Methoxybenzoic acid (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-6,9,12b-tris(acetoxy)-4-[3-(4-benzoylphenyl)-2(E)-propenoyloxy]-11-hydroxy-4a,8,13,13-tetramethyl-5-oxo-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl ester

【CA登记号】

【分子式】C₅₀H₅₂O₁₅

【分子量】892.96294

【开发单位】Roswell Park Memorial Inst. (Originator), State University of New York,Stony Brook (Originator)

【药理作用】Modulators of the Therapeutic Activity of Antineoplastic Agents, Multidrug Resistance Modulators, ONCOLYTIC DRUGS

合成路线1 合成路线2

合成路线1

10-Deacetylbaccatin III (I) was protected by treatment with triethylsilyl chloride and imidazole, and the resulting trisilylated compound (II) was debenzoylated to diol (III) by using Red-Al(R). Coupling of (III) with m-anisic acid (IV) yielded the m-methoxybenzoate ester (V). Complete desilylation of (V), followed by selective resilylation at C-7 with triethylsilyl chloride, furnished (VI). Acylation at C-10 and C-13 by means of Ac2O and DMAP, followed by desilylation, gave the modified baccatin (VII).

参考文献中间体

【1】 Strum, M.; et al.; Synthesis and SAR of new taxane reversal agents. 221st ACS Natl Meet (April 1 2001, San Diego) 2001, Abst MEDI 131.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	10467	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,9,12,15-tetrahydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate	32981-86-5	C₂₉H₃₆O₁₀	详情	详情
(II)	51201	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12,15-tris[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₄₇H₇₈O₁₀Si₃	详情	详情
(III)	51202	(1S,2S,3R,7R,9S,10S,12R,15S)-1,2-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9,12,15-tris[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-4-yl acetate		C₄₀H₇₄O₉Si₃	详情	详情
(IV)	28559	m-Anisic acid; 3-Methoxybenzoic acid	586-38-9	C₈H₈O₃	详情	详情
(V)	51203	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12,15-tris[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl 3-methoxybenzoate		C₄₈H₈₀O₁₁Si₃	详情	详情
(VI)	51204	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,12,15-trihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl 3-methoxybenzoate		C₃₆H₅₂O₁₁Si	详情	详情
(VII)	51205	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12,15-tris(acetoxy)-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl 3-methoxybenzoate		C₃₄H₄₂O₁₃	详情	详情

合成路线2

Heck coupling between 4-bromobenzophenone (VIII) and methyl acrylate (IX) in the presence of palladium diacetate gave the unsaturated ester (X). Subsequent basic hydrolysis of the methyl ester group of (X) yielded p-benzoylcinnamic acid (XI). The title compound was then obtained by the coupling of acid (XI) with the precursor baccatin (VII) in the presence of EDC and DMAP.

参考文献中间体

【1】 Strum, M.; et al.; Synthesis and SAR of new taxane reversal agents. 221st ACS Natl Meet (April 1 2001, San Diego) 2001, Abst MEDI 131.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	51205	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12,15-tris(acetoxy)-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl 3-methoxybenzoate		C₃₄H₄₂O₁₃	详情	详情
(VIII)	18447	(4-bromophenyl)(phenyl)methanone	90-90-4	C₁₃H₉BrO	详情	详情
(IX)	14156	methyl acrylate	96-33-3	C₄H₆O₂	详情	详情
(X)	18449	methyl (E)-3-(4-benzoylphenyl)-2-propenoate		C₁₇H₁₄O₃	详情	详情
(XI)	18450	(E)-3-(4-benzoylphenyl)-2-propenoic acid		C₁₆H₁₂O₃	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)