[(3aR,4R,6R,6aS)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methanol -Drug Synthesis Database

【结构式】

【分子编号】17560

【品名】[(3aR,4R,6R,6aS)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methanol

【CA登记号】362-75-4

【分子式】C₁₃H₁₇N₅O₄

【分子量】307.30928

【元素组成】C 50.81% H 5.58% N 22.79% O 20.83%

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：(I)

The oxidation of 2',3'-isopropylideneadenosine (I) with potassium permanganate gives 2',3'-isopropylideneadenosine-5'-carboxylic acid (II) which with SOCl2 affords 2',3'-isopropylideneadenosine-5'-carbonyl chloride (III), which is treated first with dry liquid ethylamine and then hydrolyzed with aqueous hydrochloric acid.

参考文献中间体

合成目标

【1】 Stein, H.H.; Prasad, R.N.; US 4029884 .
【2】 Stein, H.H.; Prasad, R.N.; US 3830796 .
【3】 Stein, H.H.; Prasad, R.N.; US 3914414 .
【4】 Stein, H.H.; Prasad, R.N.; US 3914415 .
【5】 Stein, H.H.; Prasad, R.N; US 3931401 .
【6】 Serradell, M.N.; Blancafort, P.; Castaner, J.; Hopkins, S.J.; NECA. Drugs Fut 1981, 6, 10, 627.
【7】 Stein, H.H.; Prasad, R.N.; US 3966917 .
【8】 Tietje, K.; Prasad, R.N.; N1,N6-Etheno-adenosine 5'-(N-ethylcarboxamide). Nucleic Acid Chemistry 1978, 2, 701-707.
【9】 Harman, R.E.; et al.; Permanganate oxidation of purine nucleosides. Chem Ind 1969, 1141.
【10】 Savic, M.; Brondyk, H.; Egan, R.S.; Bariana, D.S.; Fung, A.; Tietje, K.; Prasad, R.N.; Stein, H.H.; Modifications of the 5' position of purine nucleosides. 2. Synthesis and some cardiovascular properties of adenosine-5'-(N-substituted)carboxamides. J Med Chem 1980, 23, 3, 313-319.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	10928	Ethanamine	75-04-7	C₂H₇N	详情	详情
(I)	17560	[(3aR,4R,6R,6aS)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methanol	362-75-4	C₁₃H₁₇N₅O₄	详情	详情
(II)	39020	(3aR,4S,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carboxylic acid		C₁₃H₁₅N₅O₅	详情	详情
(III)	39021	(3aR,4S,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carbonyl chloride		C₁₃H₁₄ClN₅O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

A new synthesis of neplanocin A has been reported: The ring opening of 2',3'-O-isopropylideneadenine (I) with diisobutylaluminum hydride (DIBAL) in THF gives (2S,3R,4R)-9-[4,5-dihydroxy-2,3-(isopropylidenedioxy)pentyl]adenosine (II), which is partially protected with tert-butyldimethylsilyl chloride (TBDMS-Cl) and imidazole in DMF yielding the monosilylated compound (III). The Dess-Martin oxidation of (III) in dichloromethane affords the correponding ketone (IV), which is cyclized with the lithium derivative of the trimethylsilyl diazomethane in THF/hexane to give the proteced compound 2,3-O-isopropylidene-4'-O-(tert-butyldimethylsilyl)neplanocin A (V). Finally, this compound is deprotected by the usual deprotection methods.

参考文献中间体

合成目标

【1】 Niizuma, S.; Matsuda, A.; Shuto, S.; New neplanocin analogues. 10. The conversion of adenosine to neplanocin A, a carbocyclic nucleoside antibiotic with potent antiviral activity. Tetrahedron 1997, 53, 40, 13621.

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)	17560	[(3aR,4R,6R,6aS)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methanol	362-75-4	C₁₃H₁₇N₅O₄	详情	详情
(II)	17561	(1R)-1-[(4R,5R)-5-[(6-amino-9H-purin-9-yl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-1,2-ethanediol		C₁₃H₁₉N₅O₄	详情	详情
(III)	17562	(1R)-1-[(4R,5R)-5-[(6-amino-9H-purin-9-yl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-2-[[tert-butyl(dimethyl)silyl]oxy]-1-ethanol		C₁₉H₃₃N₅O₄Si	详情	详情
(IV)	17563	1-[(4S,5R)-5-[(6-amino-9H-purin-9-yl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-2-[[tert-butyl(dimethyl)silyl]oxy]-1-ethanone		C₁₉H₃₁N₅O₄Si	详情	详情
(V)	17564	9-[(3aR,4R,6aR)-6-([[tert-butyl(dimethyl)silyl]oxy]methyl)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-9H-purin-6-ylamine		C₂₀H₃₁N₅O₃Si	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Coupling of 2',3'-isopropylideneadenosine (I) with N-Boc-methionine (II) by means of DCC provided ester (III). Subsequent deprotection of (III) under acidic conditions yielded the title compound.

参考文献中间体

合成目标

【1】 Kang, M.K.; Kang, S.U.; Kim, S.; Chun, M.W.; Jo, Y.J.; Kwak, J.H.; Lee, J.; Methionyl adenylate analogues as inhibitors of methionyl-tRNA synthetase. Bioorg Med Chem Lett 1999, 9, 10, 1365.

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)	17560	[(3aR,4R,6R,6aS)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methanol	362-75-4	C₁₃H₁₇N₅O₄	详情	详情
(II)	26710	(2R)-2-[(tert-butoxycarbonyl)amino]-4-(methylsulfanyl)butyric acid	5241-66-7	C₁₀H₁₉NO₄S	详情	详情
(III)	30812	[(3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methyl (2S)-2-[(tert-butoxycarbonyl)amino]-4-(methylsulfanyl)butanoate		C₂₃H₃₄N₆O₇S	详情	详情

合成路线4

该中间体在本合成路线中的序号：(IV)

The condensation between N-Boc-methionine (I) and O-(4-methoxybenzyl)hydroxylamine hydrochloride (II) gave the hydroxamate (III), which was then coupled with 2',3'-isopropylideneadenosine (IV) under Mitsunobu conditions to provide adduct (V). Subsequent deprotection with trifluoroacetic acid and anisole yielded the title compound.

参考文献中间体

合成目标

【1】 Kang, M.K.; Kang, S.U.; Kim, S.; Chun, M.W.; Jo, Y.J.; Kwak, J.H.; Lee, J.; Methionyl adenylate analogues as inhibitors of methionyl-tRNA synthetase. Bioorg Med Chem Lett 1999, 9, 10, 1365.

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)	26710	(2R)-2-[(tert-butoxycarbonyl)amino]-4-(methylsulfanyl)butyric acid	5241-66-7	C₁₀H₁₉NO₄S	详情	详情
(II)	30813	1-[(aminooxy)methyl]-4-methoxybenzene; O-(4-methoxybenzyl)hydroxylamine		C₈H₁₁NO₂	详情	详情
(III)	30814	tert-butyl (1S)-1-([[(4-methoxybenzyl)oxy]amino]carbonyl)-3-(methylsulfanyl)propylcarbamate		C₁₈H₂₈N₂O₅S	详情	详情
(IV)	17560	[(3aR,4R,6R,6aS)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methanol	362-75-4	C₁₃H₁₇N₅O₄	详情	详情
(V)	30815	tert-butyl (1S)-1-([[[(3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methyl][(4-methoxybenzyl)oxy]amino]carbonyl)-3-(methylsulfanyl)propylcarbamate		C₃₁H₄₃N₇O₈S	详情	详情

Extended Information