Adarotene，ST-1926, -Drug Synthesis Database

【结构式】

【药物名称】Adarotene，ST-1926

【化学名称】3-[3'-(1-Adamantyl)-4'-hydroxybiphenyl-4-yl]-2(E)-propenoic acid

【CA登记号】496868-77-0

【分子式】C₂₅H₂₆O₃

【分子量】374.48417

【开发单位】Sigma-Tau (Originator)

【药理作用】ONCOLYTIC DRUGS, Apoptosis Inducers, DNA-Damaging Drugs

合成路线1 合成路线2

合成路线1

Friedel-Crafts condensation of 4'-bromobiphenyl-4-ol (I) with 1-adamantanol (II) affords the adamantanylbiphenyl derivative (III). This is then subjected to Heck coupling with methyl acrylate (IV) to produce the biphenylyl acrylate (V). Finally, basic hydrolysis of ester (V) leads to the title carboxylic acid.

参考文献中间体

【1】 Cincinelli, R.; Dallavalle, S.; Merlini, L.; Penco, S.; Pisano, C.; Carminati, P.; Giannini, G.; Vesci, L.; Gaetano, C.; Illy, B.; Zuco, V.; Supino, R.; Zunino, F.; A novel atypical retinoid endowed with proapoptotic and antitumor activity. J Med Chem 2003, 46, 6, 909.
【2】 Penco, S.; Merlini, L.; Giannini, G.; Vesci, L.; Pisano, C.; Dallavalle, S. (Sigma-Tau Industrie Farmaceutiche Riunite SpA); Retinoid derivs. with antiangiogenic, antitumoral and proapoptotic activities. WO 0311808 .

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)	48853	4-(4-Bromophenyl)phenol; 4-(4'-Bromophenyl)phenol; 4-Bromo-4'-hydroxybiphenyl	29558-77-8	C₁₂H₉BrO	详情	详情
(II)	52642	1-Adamantanol; 1-Hydroxyadamantane; Tricyclo[3.3.1.1]decan-1-ol	768-95-6	C₁₀H₁₆O	详情	详情
(III)	63330	4'-bromo-3-tricyclo[3.3.1.1~3,7~]dec-1-yl[1,1'-biphenyl]-4-ol		C₂₂H₂₃BrO	详情	详情
(IV)	14156	methyl acrylate	96-33-3	C₄H₆O₂	详情	详情
(V)	63331	methyl 3-(4'-hydroxy-3'-tricyclo[3.3.1.1~3,7~]dec-1-yl[1,1'-biphenyl]-4-yl)-2-propenoate		C₂₆H₂₈O₃	详情	详情

合成路线2

In an alternative method, 4-(t-butyldimethylsilyloxy)-3-(1-adamantyl)bromobenzene (I) undergoes Suzuki coupling with 4-formylbenzeneboronic acid (II) to provide the biphenyl aldehyde (III). Subsequent Wittig condensation of (III) with methyl triphenylphosphoranylideneacetate (IV) yields the unsaturated ester (V). This is finally hydrolyzed with LiOH to furnish the title compound.

参考文献中间体

【1】 Penco, S.; Merlini, L.; Giannini, G.; Vesci, L.; Pisano, C.; Dallavalle, S. (Sigma-Tau Industrie Farmaceutiche Riunite SpA); Retinoid derivs. with antiangiogenic, antitumoral and proapoptotic activities. WO 0311808 .

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)	63332	4-bromo-2-tricyclo[3.3.1.1~3,7~]dec-1-ylphenyl (1,1-dimethylethyl)(dimethyl)silyl ether; [(4-bromo-2-tricyclo[3.3.1.1~3,7~]dec-1-ylphenyl)oxy](1,1-dimethylethyl)dimethylsilane		C₂₂H₃₃BrOSi	详情	详情
(II)	61564	4-Formylphenylboronic acid; 4-Formylbenzeneboronic acid; 4-Boronobenzaldehyde; Benzaldehyde-4-boronic acid; 4-Formylphenylboronic acid	87199-17-5	C₇H₇BO₃	详情	详情
(III)	63333	4'-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-3'-tricyclo[3.3.1.1~3,7~]dec-1-yl[1,1'-biphenyl]-4-carbaldehyde		C₂₉H₃₈O₂Si	详情	详情
(IV)	14689	Methyl (triphenylphosphoranylidene)acetate; (methoxycarbonylmethylene)triphenylphosphorane；Methyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate	2605-67-6	C₂₁H₁₉O₂P	详情	详情
(V)	63334	methyl 3-(4'-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-3'-tricyclo[3.3.1.1~3,7~]dec-1-yl[1,1'-biphenyl]-4-yl)-2-propenoate		C₃₂H₄₂O₃Si	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)