ME-2303, FAD-104, -Drug Synthesis Database

【结构式】

【药物名称】ME-2303, FAD-104

【化学名称】7-O-(2,6-Dideoxy-2-fluoro-alpha-L-talopyranosyl)pimelyladryamycinone
　　　　　　(8S,10S)-8-(6-Carboxyhexanoyloxyacetyl)-10-[(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl)oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5,12-naphthacenedione
　　　　　　7-O-(2,6-Dideoxy-2-fluoro-alpha-L-talopyranosyl)adriamycinone-14-O-hemipimelate

【CA登记号】116521-53-0

【分子式】C₃₄H₃₇FO₁₅

【分子量】704.66339

【开发单位】Meiji Seika (Originator)

【药理作用】Antibiotics and Alkaloids, Antineoplastic Antibiotics, ONCOLYTIC DRUGS

合成路线1 合成路线2

合成路线1

L-Fucose (I) is converted successively to its methyl glucoside (II), the 3,4-O-isopropylidene derivative (III), the 2-O-acetyl derivative (IV), the 2-O-acetyl-L-methylfucoside (V), the tosylate (VI), the 4-O-benzyl derivative (VII) and finally, through various steps, the 3,4-O-diacetyl-2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl bromide (VIII). The condensation of (VIII) with daunomycinone (IX) gives the daunomycin derivative (X), which is converted to the isopropylidene derivative (XI). The bromination of (XI) affords the bromo derivative (XII).

参考文献中间体

【1】 Hoshi, A.; Prous, J.; Castaner, J.; ME2303. Drugs Fut 1989, 14, 8, 756.
【2】 Omoto, S.; Kondo, S.; Fukatsu, S.; Takeuchi, T.; Umezawa, K.; Tsuchiya, T.; Umezawa, S.; Biological properties of ME2303 (FAD-104), a new anthracycline. Drug Exp Clin Res 1988, 14, 7, 435-9.

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)	21215	6-methyltetrahydro-2H-pyran-2,3,4,5-tetrol		C₆H₁₂O₅	详情	详情
(II)	21216	2-methoxy-6-methyltetrahydro-2H-pyran-3,4,5-triol	14917-55-6	C₇H₁₄O₅	详情	详情
(III)	21217	8-methoxy-3,3,6-trimethylhexahydro-2H,6H-pyrano[3,4-b][1,4]dioxepin-9-ol		C₁₂H₂₂O₅	详情	详情
(IV)	21218	8-methoxy-3,3,6-trimethylhexahydro-2H,6H-pyrano[3,4-b][1,4]dioxepin-9-yl acetate		C₁₄H₂₄O₆	详情	详情
(V)	21219	4,5-dihydroxy-2-methoxy-6-methyltetrahydro-2H-pyran-3-yl acetate		C₉H₁₆O₆	详情	详情
(VI)	21220	5-hydroxy-2-methoxy-6-methyl-4-[[(4-methylphenyl)sulfonyl]oxy]tetrahydro-2H-pyran-3-yl acetate		C₁₆H₂₂O₈S	详情	详情
(VII)	21221	5-(acetoxy)-6-methoxy-2-methyl-4-[[(4-methylphenyl)sulfonyl]oxy]tetrahydro-2H-pyran-3-yl 2-phenylacetate		C₂₄H₂₈O₉S	详情	详情
(VIII)	21222	3-(acetoxy)-6-bromo-5-fluoro-2-methyltetrahydro-2H-pyran-4-yl acetate		C₁₀H₁₄BrFO₅	详情	详情
(IX)	16223	(8S,10S)-8-acetyl-6,8,10,11-tetrahydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione	21794-55-8	C₂₁H₁₈O₈	详情	详情
(X)	21224	3-(acetoxy)-6-[[(1S,3S)-3-acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-1-naphthacenyl]oxy]-5-fluoro-2-methyltetrahydro-2H-pyran-4-yl acetate		C₃₁H₃₁FO₁₃	详情	详情
(XI)	21225	(8S,10S)-8-acetyl-10-[(9-fluoro-3,3,6-trimethylhexahydro-2H,6H-pyrano[3,4-b][1,4]dioxepin-8-yl)oxy]-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione		C₃₂H₃₅FO₁₁	详情	详情
(XII)	21226	(8R,10S)-8-(2-bromoacetyl)-10-[(9-fluoro-3,3,6-trimethylhexahydro-2H,6H-pyrano[3,4-b][1,4]dioxepin-8-yl)oxy]-6,11-dihydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione		C₃₂H₃₄BrFO₁₀	详情	详情

合成路线2

The condensation of (XII) with monosodium pimelate (XIII) in acetone - water yields the protected hemipimelate (XIV), which is finally treated with hot acetic acid - water.

参考文献中间体

【1】 Umezawa, H.; Umezawa, S.; Tsuchiya, T.; Takeuchi, T.; Takagi, Y.; Yoneda, T.; Fukatsu, S. (Microbial Chemistry Research Foundation); Novel anthracycline derivs., a process for preparing them and their use as medicaments. EP 0275431; JP 1988141992 .
【2】 Tsuchiya, T.; Takagi, Y.; Umezawa, S.; Takeuchi, T.; Komuro, K.; Nosaka, C.; Umezawa, H.; Fukatsu, S.; Yoneta, T.; Synthesis and antitumor activities of 14-O-acyl derivatives of 7-O-(2, 6-dideoxy-2-fluoro-alpha-L-talopyranosyl)adriamycin. J Antibiot 1988, 41, 7, 988-91.
【3】 Hoshi, A.; Prous, J.; Castaner, J.; ME2303. Drugs Fut 1989, 14, 8, 756.
【4】 Omoto, S.; Kondo, S.; Fukatsu, S.; Takeuchi, T.; Umezawa, K.; Tsuchiya, T.; Umezawa, S.; Biological properties of ME2303 (FAD-104), a new anthracycline. Drug Exp Clin Res 1988, 14, 7, 435-9.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XII)	21226	(8R,10S)-8-(2-bromoacetyl)-10-[(9-fluoro-3,3,6-trimethylhexahydro-2H,6H-pyrano[3,4-b][1,4]dioxepin-8-yl)oxy]-6,11-dihydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione	C₃₂H₃₄BrFO₁₀	详情	详情
(XIII)	21227	sodium 6-carboxyhexanoate	C₇H₁₁NaO₄	详情	详情
(XIV)	21228	7-(2-[(2S,4S)-4-[(9-fluoro-3,3,6-trimethylhexahydro-2H,6H-pyrano[3,4-b][1,4]dioxepin-8-yl)oxy]-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-2-naphthacenyl]-2-oxoethoxy)-7-oxoheptanoic acid	C₃₉H₄₅FO₁₅	详情	详情

Extended Information