[(2S)-5-oxotetrahydro-2-furanyl]methyl benzoate -Drug Synthesis Database

【结构式】

【分子编号】12009

【品名】[(2S)-5-oxotetrahydro-2-furanyl]methyl benzoate

【CA登记号】

【分子式】C₁₂H₁₂O₄

【分子量】220.22488

【元素组成】C 65.45% H 5.49% O 29.06%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(V)

A new synthesis of 2',3'-dideoxyadenosine has been described: The stereospecific deamination - lactonization of L-glutamic acid (I) with NaNO2 - HCl in water gives (S)-(+)-gamma-carboxy-gamma-butyrolactone (II), which is esterified with ethanol - p-toluenesulfonic acid to the ester (III). The selective reduction of (III) with NaBH4 in ethanol yields (S)-(+)-gamma-(hydroxymethyl)-gamma-butyrolactone (IV), which is benzoylated with benzoyl chloride as usual, affording the benzoate (V). The selective reduction of (V) with disiamyl borane in THF gives the alcohol (VI), which is acetylated with acetic anhydride in pyridine to the acetate (VII). The reaction of (VII) with trimethylsilyl bromide in dichloromethane yields the tetrahydrofuryl bromide (VIII), which is condensed with the silylated adenine (IX) to afford 5'-O-benzoyl-2',3'-dideoxyadenosine (X). Finally, this compound is deprotected with NH3 in methanol.

参考文献中间体

合成目标

【1】 Farina, V.; Benigni, D.A.; 2',3'-dideoxynucleosides for AIDS chemotherapy. Tetrahedron Lett 1988, 29, 11, 1239-42.

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)	12005	L-2-Amino propane dicarboxylic acid; (-)-2-Aminoglutaric acid; L-2-Aminopentanoic acid; L-Glutamic acid	56-86-0	C₅H₉NO₄	详情	详情
(II)	12006	(R)-(-)-5-Oxo-2-tetrahydrofurancarboxylic acid; (2S)-5-oxotetrahydro-2-furancarboxylic acid	53558-93-3	C₅H₆O₄	详情	详情
(III)	12007	ethyl (2S)-5-oxotetrahydro-2-furancarboxylate; (S)-(+)-gamma-Ethoxycarbonyl-gamma-butyrolactone	55094-96-7	C₇H₁₀O₄	详情	详情
(IV)	12008	(5S)-5-(Hydroxymethyl)dihydro-2(3H)-furanone; (S)-(+)-Dihydro-5-(hydroxymethyl)-2(3h)-furanone	32780-06-6	C₅H₈O₃	详情	详情
(V)	12009	[(2S)-5-oxotetrahydro-2-furanyl]methyl benzoate		C₁₂H₁₂O₄	详情	详情
(VI)	12010	[(2S)-5-hydroxytetrahydro-2-furanyl]methyl benzoate		C₁₂H₁₄O₄	详情	详情
(VII)	12011	[(2S)-5-(acetoxy)tetrahydro-2-furanyl]methyl benzoate		C₁₄H₁₆O₅	详情	详情
(VIII)	12012	[(2S)-5-bromotetrahydro-2-furanyl]methyl benzoate		C₁₂H₁₃BrO₃	详情	详情
(IX)	12013	N,9-Bis(trimethylsilyl)-9H-purin-6-amine; N-(Trimethylsilyl)-N-[9-(trimethylsilyl)-9H-purin-6-yl]amine	17995-04-9	C₁₁H₂₁N₅Si₂	详情	详情
(X)	12014	[(2S,5R)-5-(6-amino-9H-purin-9-yl)tetrahydro-2-furanyl]methyl benzoate		C₁₇H₁₇N₅O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

1) The stereospecific deamination - lactonization of L-glutamic acid (I) with NaNO2 - HCl in water gives (S)-(+)-gamma-carboxy-gamma-butyrolactone (II), which is esterified with ethanol and p-toluenesulfonic acid in the usual way, yielding the ethyl ester (III). The selective reduction of (III) with NaBH4 in ethanol affords (S)-(+)-gamma-(hydroxymethyl)-gamma-butyrolactone (IV), which is benzoylated with benzoyl chloride to the benzoate (V). The selective reduction of (V) with disiamyl borane in THF yields the alcohol (VI), which is acetylated with acetic anhydride in pyridine to the acetate (VII). The reaction of (VII) with trimethylsilyl bromide in dichloromethane affords the tetrahydrofuryl bromide (VIII), which is then condensed with the adenine (IX), giving 5'-O-benzoyl-2',3'-dideoxyadenosine (X). The deprotection of (X) with NH3 in methanol yields 2',3'-dideoxyadenosine, which is finally deaminated enzymatically with the enzyme adenosine deaminase.

参考文献中间体

合成目标

【1】 Farina, V.; Benigni, D.A.; 2',3'-dideoxynucleosides for AIDS chemotherapy. Tetrahedron Lett 1988, 29, 11, 1239-42.
【2】 Prous, J.; Castaner, J.; DIDEOXYINOSINE. Drugs Fut 1990, 15, 6, 569.
【3】 Taniguchi, M.; Koga, K.; Yamada, S.; Stereoselective synthesis of D-ribose from L-glutamic acid. Tetrahedron 1974, 30, 3547-52.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	60593	p-xylene		C₈H₁₀	详情	详情
(I)	12005	L-2-Amino propane dicarboxylic acid; (-)-2-Aminoglutaric acid; L-2-Aminopentanoic acid; L-Glutamic acid	56-86-0	C₅H₉NO₄	详情	详情
(II)	12006	(R)-(-)-5-Oxo-2-tetrahydrofurancarboxylic acid; (2S)-5-oxotetrahydro-2-furancarboxylic acid	53558-93-3	C₅H₆O₄	详情	详情
(III)	12007	ethyl (2S)-5-oxotetrahydro-2-furancarboxylate; (S)-(+)-gamma-Ethoxycarbonyl-gamma-butyrolactone	55094-96-7	C₇H₁₀O₄	详情	详情
(IV)	12008	(5S)-5-(Hydroxymethyl)dihydro-2(3H)-furanone; (S)-(+)-Dihydro-5-(hydroxymethyl)-2(3h)-furanone	32780-06-6	C₅H₈O₃	详情	详情
(V)	12009	[(2S)-5-oxotetrahydro-2-furanyl]methyl benzoate		C₁₂H₁₂O₄	详情	详情
(VI)	12010	[(2S)-5-hydroxytetrahydro-2-furanyl]methyl benzoate		C₁₂H₁₄O₄	详情	详情
(VII)	12011	[(2S)-5-(acetoxy)tetrahydro-2-furanyl]methyl benzoate		C₁₄H₁₆O₅	详情	详情
(VIII)	12012	[(2S)-5-bromotetrahydro-2-furanyl]methyl benzoate		C₁₂H₁₃BrO₃	详情	详情
(IX)	12013	N,9-Bis(trimethylsilyl)-9H-purin-6-amine; N-(Trimethylsilyl)-N-[9-(trimethylsilyl)-9H-purin-6-yl]amine	17995-04-9	C₁₁H₂₁N₅Si₂	详情	详情
(X)	12014	[(2S,5R)-5-(6-amino-9H-purin-9-yl)tetrahydro-2-furanyl]methyl benzoate		C₁₇H₁₇N₅O₃	详情	详情
(XI)	12787	[(2S,5R)-5-(6-Amino-9H-purin-9-yl)tetrahydro-2-furanyl]methanol; Dideoxyadenosine	4097-22-7	C₁₀H₁₃N₅O₂	详情	详情

Extended Information