(2E)-1-bromo-3,7-dimethyl-2,6-octadiene; trans-Geranyl bromide; Geranyl bromide -Drug Synthesis Database

【结构式】

【分子编号】31116

【品名】(2E)-1-bromo-3,7-dimethyl-2,6-octadiene; trans-Geranyl bromide; Geranyl bromide

【CA登记号】6138-90-5

【分子式】C₁₀H₁₇Br

【分子量】217.14898

【元素组成】C 55.31% H 7.89% Br 36.8%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(VIII)

The condensation of genanyl bromide (VIII) with methyl 4,4-dimethoxyacetylacetate (IX) by means of sodium ethoxide in refluxing ethanol gives 1,1-dimethoxy-6,10-dimethyl-5,9-undecadiene-2-one (X), which is submitted to a Wittig condensation with (4-methyl-6-tetrahydropyranyloxy-4-hexenyl)triphenyl phosphonium iodide by means of n-butyllithium in hexane yielding 7-formyl-3,11,15-trimethyl-2,6,10,14-hexadecatetraen-1-ol (XII). Finally, this compound is reduced with NaBH4 in ethanol.

参考文献中间体

合成目标

【1】 Mishima, H.; Ogiso, A.; Kobayashi, S. (Sankyo Co., Ltd.); Polyprenyl piperazines. DE 2717990; FR 2348907; FR 2422617; GB 1534111; JP 52131507; US 4151357 .
【2】 Castaner, J.; Serradell, M.N.; Blancafort, P.; Plaunotol. Drugs Fut 1983, 8, 11, 930.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	31116	(2E)-1-bromo-3,7-dimethyl-2,6-octadiene; trans-Geranyl bromide; Geranyl bromide	6138-90-5	C₁₀H₁₇Br	详情	详情
(IX)	31117	methyl 4,4-dimethoxy-3-oxobutanoate		C₇H₁₂O₅	详情	详情
(X)	31118	(5E)-1,1-dimethoxy-6,10-dimethyl-5,9-undecadien-2-one		C₁₅H₂₆O₃	详情	详情
(XI)	31119	[(E)-4-methyl-7-(tetrahydro-2H-pyran-2-yloxy)-4-heptenyl](triphenyl)phosphonium iodide		C₃₁H₃₈IO₂P	详情	详情
(XII)	31120	(5E)-2-[(Z,4E)-6-hydroxy-4-methyl-4-hexenylidene]-6,10-dimethyl-5,9-undecadienal		C₂₀H₃₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

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

合成目标

【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3

该中间体在本合成路线中的序号：(III)

Commercial silybin (I) was oxidized to dehydrosilybin (II) employing iodine and KOAc in HOAc. Alkylation of (II) with geranyl bromide (III) in the presence of tetraethylammonium hydroxide provided a mixture of the desired 8-geranyl dehydrosilybin along with minor amounts of the 6-geranyl isomer (IV), which were separated by chromatography.

参考文献中间体

合成目标

【1】 Barron, D.; Di Pietro, A.; El Kirat, K.; Conseil, G.; Comte, G.; Maitrejean, M.; The flavanolignan silybin and its hemisynthetic derivatives, a novel series of potential modulators of P-glycoprotein. Bioorg Med Chem Lett 2000, 10, 2, 157.

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)	46432	(2R,3R)-3,5,7-trihydroxy-2-[3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-2,3-dihydro-4H-chromen-4-one		C₂₅H₂₂O₁₀	详情	详情
(II)	46433	3,5,7-trihydroxy-2-[3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-4H-chromen-4-one		C₂₅H₂₀O₁₀	详情	详情
(III)	31116	(2E)-1-bromo-3,7-dimethyl-2,6-octadiene; trans-Geranyl bromide; Geranyl bromide	6138-90-5	C₁₀H₁₇Br	详情	详情
(IV)	46434	6-[(2E)-3,7-dimethyl-2,6-octadienyl]-3,5,7-trihydroxy-2-[3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]-4H-chromen-4-one		C₃₅H₃₆O₁₀	详情	详情

合成路线4

该中间体在本合成路线中的序号：(VIII)

In an adapted method, complete solution-phase synthesis of SQ-109 is achieved by the substitution of (2E)-1-bromo-3,7-dimethylocta-2,6-diene (VIII) by ethylene diamine (IX) at –78 °C in dry DCM to give (E)-N’-(3,7-dimethylocta-2,6-dienyl)ethane-1,2-diamine (X) (4, 5). Finally, amine (X) is made to undergo reductive amination with 2-adamantanone (XI) in MeOH using NaBH4 under an N2 atmosphere overnight to give SQ-109, which can be extracted with ethyl acetate or converted to a hydrochloride salt using HCl and MeOH. Scheme 2.

参考文献中间体

合成目标

【4】 Onajole, O.K., Govender, P., van Helden, P.D., Kruger, H.G., Maguire, G.E., Wiid, I., Govender, T. Synthesis and evaluation of SQ109 analogues as potential anti-tuberculosis candidates. Eur J Med Chem 2010, 45(5): 2075-9.
【5】 Onajole, O.K., Sosibo, S., Govender, P. et al. Novel linear diamine disubstituted polycyclic ‘cage’ derivatives as potential antimycobacterial candidates. Chem Biol Drug Design 2011, 78(6): 1022-30.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	31116	(2E)-1-bromo-3,7-dimethyl-2,6-octadiene; trans-Geranyl bromide; Geranyl bromide	6138-90-5	C₁₀H₁₇Br	详情	详情
(IX)	14754	ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine	107-15-3	C₂H₈N₂	详情	详情
(X)	66063	(E)-N’-(3,7-dimethylocta-2,6-dienyl)ethane-1,2-diamine		C₁₂H₂₄N₂	详情	详情
(XI)	40404	2-adamantanone	700-58-3	C₁₀H₁₄O	详情	详情

Extended Information