-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】N-[7-(Hydroxymethyl)-3,11,15-trimethylhexadeca-2(E),6(Z),10(E),14-tetraenyl]-N'-(2-phenylethyl)thiourea

【CA登记号】191042-72-5

【分子式】C₂₉H₄₄N₂OS

【分子量】468.75083

【开发单位】Sankyo (Originator)

【药理作用】Anti-Helicobacter Pylori Agents, Antiulcer Drugs, GASTROINTESTINAL DRUGS

合成路线1 合成路线2

合成路线1

The alkylation of ethyl 4,4-diethoxyacetoacetate (I) with geranyl bromide (II) gave ketoester (III), which was further decarbethoxylated upon treatment with KOH in refluxing H2O - EtOH yielding (IV). Wittig condensation of the resulting alpha-acetal ketone (IV) with phosphonium salt (V) in the presence of KH and crown ether provided the Z olefin (VI) as the major isomer. Deprotection of the silyl ether of (VI) with tetrabutylammonium fluoride gave alcohol (VII), which was coupled with phthalimide under Mitsunobu conditions to yield (VIII). Hydrolysis of the acetal group of (VIII) with aqueous AcOH gave aldehyde (IX).

参考文献中间体

【1】 Masuda, K.; Akiyama, T.; Tago, K.; Arai, M.; Minami, E.; Kogen, H.; A highly stereoselective synthesis of plaunotol and its thiourea derivatives as potent antibacterial agents against Helicobacter pylori. Bioorg Med Chem Lett 1999, 9, 10, 1347.

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)	31358	ethyl 4,4-diethoxy-3-oxobutanoate		C₁₀H₁₈O₅	详情	详情
(II)	31116	(2E)-1-bromo-3,7-dimethyl-2,6-octadiene; trans-Geranyl bromide; Geranyl bromide	6138-90-5	C₁₀H₁₇Br	详情	详情
(III)	31359	ethyl (4E)-2-(2,2-diethoxyacetyl)-5,9-dimethyl-4,8-decadienoate		C₂₀H₃₄O₅	详情	详情
(IV)	31360	(5E)-1,1-diethoxy-6,10-dimethyl-5,9-undecadien-2-one		C₁₇H₃₀O₃	详情	详情
(V)	31361	((E)-6-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-4-hexenyl)(triphenyl)phosphonium iodide		C₃₁H₄₂IOPSi	详情	详情
(VI)	31365	tert-butyl[[(2E,6Z,10E)-7-(diethoxymethyl)-3,11,15-trimethyl-2,6,10,14-hexadecatetraenyl]oxy]dimethylsilane; tert-butyl(dimethyl)silyl (2E,6Z,10E)-7-(diethoxymethyl)-3,11,15-trimethyl-2,6,10,14-hexadecatetraenyl ether		C₃₀H₅₆O₃Si	详情	详情
(VII)	31362	(2E,6Z,10E)-7-(diethoxymethyl)-3,11,15-trimethyl-2,6,10,14-hexadecatetraen-1-ol		C₂₄H₄₂O₃	详情	详情
(VIII)	31363	2-[(2E,6Z,10E)-7-(diethoxymethyl)-3,11,15-trimethyl-2,6,10,14-hexadecatetraenyl]-1H-isoindole-1,3(2H)-dione		C₃₂H₄₅NO₄	详情	详情
(IX)	31364	(5E)-2-[(Z,4E)-6-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-methyl-4-hexenylidene]-6,10-dimethyl-5,9-undecadienal		C₂₈H₃₅NO₃	详情	详情

合成路线2

Then, selective reduction of the aldehyde by treatment with zinc borohydride produced alcohol (X). Deprotection of the phthalimide group of (X) with butylamine gave primary amine (XI). This was finally converted to the target thiourea by treatment with phenethyl isocyanate (XII) in EtOH.

参考文献中间体

【1】 Masuda, K.; Akiyama, T.; Tago, K.; Arai, M.; Minami, E.; Kogen, H.; A highly stereoselective synthesis of plaunotol and its thiourea derivatives as potent antibacterial agents against Helicobacter pylori. Bioorg Med Chem Lett 1999, 9, 10, 1347.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IX)	31364	(5E)-2-[(Z,4E)-6-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-methyl-4-hexenylidene]-6,10-dimethyl-5,9-undecadienal		C₂₈H₃₅NO₃	详情	详情
(X)	31366	2-[(2E,6Z,10E)-7-(hydroxymethyl)-3,11,15-trimethyl-2,6,10,14-hexadecatetraenyl]-1H-isoindole-1,3(2H)-dione		C₂₈H₃₇NO₃	详情	详情
(XI)	31367	(5E)-2-[(Z,4E)-6-amino-4-methyl-4-hexenylidene]-6,10-dimethyl-5,9-undecadien-1-ol		C₂₀H₃₅NO	详情	详情
(XII)	31368	phenethyl isothiocyanate; 1-(2-isothiocyanatoethyl)benzene	2257-09-2	C₉H₉NS	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)