(2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-2-(hydroxymethyl)tetrahydro-3-furanol -Drug Synthesis Database

【结构式】

【分子编号】18061

【品名】(2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-2-(hydroxymethyl)tetrahydro-3-furanol

【CA登记号】958-09-8

【分子式】C₁₀H₁₃N₅O₃

【分子量】251.24512

【元素组成】C 47.81% H 5.22% N 27.87% O 19.1%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(VIII)

The bromination of 2'-deoxyadenosine (VIII) with Br2 in dioxane - water by means of CaCO3 or sodium acetate gives 8-bromo-2'-deoxyadenosine (IX), which by reaction with triphenylmethyl chloride in pyridine - DMF is converted into 8-bromo-2'-deoxy-5'-O-triphenylmethyladenosine (X). The reaction of (X) with p-toluenesulfonyl chloride in pyridine affords 8-bromo-5'-O-triphenylmethyl-3'-O-(p-toluenesulfonyl)-2'-deoxyadenosine (XI), which by reaction with thiourea (A) in refluxing butanol and treatment with propanol-ammonia-water is converted into 2',3'-dideoxy-8-mercapto-8,3'-anhydroadenosine (XII). Finally, this compound is desulfurized by treatment with Raney-Ni in refluxing water.

参考文献中间体

合成目标

【1】 Morio, I.; Masakatsu, K.; Nucleosides and nucleotides. XLIV. Purine cyclonucleosides. 2. Synthesis of cyclonucleosides having 8,3'-O- and -S-anhydro linkage derived from 2'-deoxyadenosine. Chem Pharm Bull 1970, 18, 12, 2441-46.
【2】 Castaner, J.; Hopkins, S.J.; Serradell, M.N.; Blancafort, P.; 2',3'-Dideoxyadenosine. Drugs Fut 1982, 7, 4, 244.

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)	10180	Thiourea	62-56-6	CH₄N₂S	详情	详情
(VIII)	18061	(2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-2-(hydroxymethyl)tetrahydro-3-furanol	958-09-8	C₁₀H₁₃N₅O₃	详情	详情
(IX)	36386	(2R,3S,5R)-5-(6-amino-8-bromo-9H-purin-9-yl)-2-(hydroxymethyl)tetrahydro-3-furanol		C₁₀H₁₂BrN₅O₃	详情	详情
(X)	36387	(2R,3S,5R)-5-(6-amino-8-bromo-9H-purin-9-yl)-2-[(trityloxy)methyl]tetrahydro-3-furanol		C₂₉H₂₆BrN₅O₃	详情	详情
(XI)	36388	(2R,3S,5R)-5-(6-amino-8-bromo-9H-purin-9-yl)-2-[(trityloxy)methyl]tetrahydro-3-furanyl 4-methylbenzenesulfonate		C₃₆H₃₂BrN₅O₅S	详情	详情
(XII)	36389	[(1S,12S,13R)-7-amino-14-oxa-11-thia-2,4,6,9-tetraazatetracyclo[10.2.1.0(2,10).0(3,8)]pentadeca-3,5,7,9-tetraen-13-yl]methanol		C₁₀H₁₁N₅O₂S	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 didanosine has been described: Treatment of 2'-deoxyadenosine (I) with adenosine deaminase (ADA) in water gives 2'-deoxyinosine (II), which is treated with vinyl acetate (III) and Candida antarctica lipase (CAL) in hot pyridine yielding 5'-O-acetyl-2'-deoxyinosine (IV). The reaction of (IV) with phenyl chlorothionoformate (V) and DMAP in acetonitrile affords the corresponding thiocarbonate (VI), which is treated with tributylstannane and AIBN in hot toluene to provide 5'-O-acetyl-2',3'-dideoxyinosine (VII). Finally, this compound is deacetylated with NH3 in methanol.

参考文献中间体

合成目标

【1】 Santaniello, E.; Ciuffreda, P.; Casati, S.; Lipase-catalyzed protection of the hydroxy groups of the nucleosides inosine and 2'-deoxyinosine: A new chemoenzymatic synthesis of the antiviral drug 2',3'-dideoxyinosine. Bioorg Med Chem Lett 1999, 9, 11, 1577.

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)	18061	(2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-2-(hydroxymethyl)tetrahydro-3-furanol	958-09-8	C₁₀H₁₃N₅O₃	详情	详情
(II)	12801	9-[(2R,4S,5R)-4-Hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-9H-purin-6-ol	890-38-0	C₁₀H₁₂N₄O₄	详情	详情
(III)	24543	vinyl acetate	108-05-4	C₄H₆O₂	详情	详情
(IV)	37609	[(2R,3S,5R)-3-hydroxy-5-(6-hydroxy-9H-purin-9-yl)tetrahydro-2-furanyl]methyl acetate		C₁₂H₁₄N₄O₅	详情	详情
(V)	25805	1-[(chlorocarbothioyl)oxy]benzene; Phenylchlorothioformate	1005-56-7	C₇H₅ClOS	详情	详情
(VI)	37610	[(2R,3S,5R)-5-(6-hydroxy-9H-purin-9-yl)-3-[(phenoxycarbothioyl)oxy]tetrahydro-2-furanyl]methyl acetate		C₁₉H₁₈N₄O₆S	详情	详情
(VII)	37611	[(2S,5R)-5-(6-hydroxy-9H-purin-9-yl)tetrahydro-2-furanyl]methyl acetate		C₁₂H₁₄N₄O₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

2'-Deoxyadenosine (I) was protected as the diacetate (II) on treatment with acetic anhydride and a catalytic amount of dimethylaminopyridine. Then, reaction with an excess of isopentyl nitrite and diiodomethane under illumination of a tungsten lamp provided iodide (III). Subsequent treatment with ethanolic methylamine effected both deacetylation and substitution of iodide to give 2'-deoxy-N6-methyladenosine (IV). Finally, this was treated with phosphoryl chloride and Proton Sponge(R) in trimethyl phosphate at 0 C, followed by quenching with triethyl ammonium bicarbonate buffer to yield the target bisphosphate.

参考文献中间体

合成目标

【1】 Camaioni, E.; et al.; Deoxyadenosine bisphosphate derivatives as potent antagonists at P2Y1 receptors. J Med Chem 1998, 41, 1, 183-190.

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)	18061	(2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-2-(hydroxymethyl)tetrahydro-3-furanol	958-09-8	C₁₀H₁₃N₅O₃	详情	详情
(II)	18062	[(2R,3S,5R)-3-(acetoxy)-5-(6-amino-9H-purin-9-yl)tetrahydro-2-furanyl]methyl acetate		C₁₄H₁₇N₅O₅	详情	详情
(III)	18063	[(2R,3S,5R)-3-(acetoxy)-5-(6-iodo-9H-purin-9-yl)tetrahydro-2-furanyl]methyl acetate		C₁₄H₁₅IN₄O₅	详情	详情
(IV)	18064	N6-Methyl-2'-deoxyadenosine; (2R,3S,5R)-2-(hydroxymethyl)-5-[6-(methylamino)-9H-purin-9-yl]tetrahydro-3-furanol	2002-35-9	C₁₁H₁₅N₅O₃	详情	详情

Extended Information