(+)-Hemipalmitoylcarnitinium, Z-15, -Drug Synthesis Database

【结构式】

【药物名称】(+)-Hemipalmitoylcarnitinium, Z-15

【化学名称】2-[6(S)-Hydroxy-4,4-dimethyl-6-pentadecylmorpholinium-2(R)-yl]acetate
　　　　　　(2S,6R)-6-(Carboxymethyl)-2-hydroxy-4,4-dimethyl-2-pentadecylmorpholinium inner salt

【CA登记号】145554-73-0, 145631-91-0 (hydrate)

【分子式】C₂₃H₄₅NO₄

【分子量】399.6194

【开发单位】Virginia Tech (Originator)

【药理作用】AIDS Medicines, Antifungal Agents, Anti-Herpes Virus Drugs, Anti-HIV Agents, ANTIINFECTIVE THERAPY, Antiviral Drugs, Contraceptives, Disorders of Sexual Function and Reproduction, Treatment of, ENDOCRINE DRUGS, Female Contraceptives, Vaginal Spermicides, Carnitine O-Palmitoyltransferase 1 (CPT-1) Inhibitors

合成路线1 合成路线2 合成路线3

合成路线1

Intermediate hydroxyester (III) has been obtained as follows: Demethylation of (R)-carnitine (I) by thiophenol in dimethylaminoethanol, followed by precipitation with LiOH, gave lithium carboxylate (II), which was esterified to (III) by treatment either with H2SO4 in MeOH or with trimethyl orthoformate in refluxing methanol.

参考文献中间体

【1】 Bryant, S.D.; Hubieki, M.P.; Robinette, R.G.; Gandourk, R.D.; Savle, P.S.; Doncel, G.F.; Acylcarnitine analogues as topical, microbicidal spermicides. Bioorg Med Chem Lett 1999, 9, 17, 2545.

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)	42353	(3R)-3-hydroxy-4-(trimethylammonio)butanoate; L(-)-Carnitine	541-15-1	C₇H₁₅NO₃	详情	详情
(II)	42354	lithium (3R)-4-(dimethylamino)-3-hydroxybutanoate		C₆H₁₂LiNO₃	详情	详情
(III)	42355	methyl (3R)-4-(dimethylamino)-3-hydroxybutanoate		C₇H₁₅NO₃	详情	详情

合成路线2

The condensation of palmitoyl chloride (IV) with diazomethane produced diazoketone (V). This was then treated with HBr to yield bromoketone (VI).

参考文献中间体

【1】 Gandour, R.D.; et al.; (+)-Hemipalmitoylcarnitinium strongly inhibits carnitine palmitoyltransfease-I in intact mitochondria. J Med Chem 1993, 36, 2, 237.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	30295	tetradecanoyl chloride	112-64-1	C₁₄H₂₇ClO	详情	详情
(V)	42356			C₁₅H₂₈N₂O	详情	详情
(VI)	42357	1-bromo-2-heptadecanone		C₁₇H₃₃BrO	详情	详情

合成路线3

In a different procedure, treatment of olefin (VII) with N-bromosuccinimide produced bromohydrin (VIII), which was further oxidized to bromoketone (VI) by means of Jones reagent. Condensation of bromoketone (VI) with aminoalcohol (III) in nitromethane furnished the morpholine derivative (IX). The ester group was finally hydrolyzed with to yield the title compound.

参考文献中间体

【1】 Bryant, S.D.; Hubieki, M.P.; Robinette, R.G.; Gandourk, R.D.; Savle, P.S.; Doncel, G.F.; Acylcarnitine analogues as topical, microbicidal spermicides. Bioorg Med Chem Lett 1999, 9, 17, 2545.
【2】 Gandour, R.D.; et al.; (+)-Hemipalmitoylcarnitinium strongly inhibits carnitine palmitoyltransfease-I in intact mitochondria. J Med Chem 1993, 36, 2, 237.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	42355	methyl (3R)-4-(dimethylamino)-3-hydroxybutanoate		C₇H₁₅NO₃	详情	详情
(VI)	42357	1-bromo-2-heptadecanone		C₁₇H₃₃BrO	详情	详情
(VII)	42358	1-heptadecene	6765-39-5	C₁₇H₃₄	详情	详情
(VIII)	42359	1-bromo-2-heptadecanol		C₁₇H₃₅BrO	详情	详情
(IX)	42360	(2S,6R)-2-hydroxy-6-(2-methoxy-2-oxoethyl)-4,4-dimethyl-2-pentadecylmorpholin-4-ium bromide		C₂₄H₄₈BrNO₄	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)