Guanosine; 2-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one -Drug Synthesis Database

【结构式】

【分子编号】38958

【品名】Guanosine; 2-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one

【CA登记号】118-00-3

【分子式】C₁₀H₁₃N₅O₅

【分子量】283.24392

【元素组成】C 42.41% H 4.63% N 24.73% O 28.24%

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：(II)

The acetylation of guanine (I) or guanosine (II) with acetic anhydride gives the diacetyl guanine (III), which is condensed with 1,4-diacetoxy-2-oxabutane (IV) by means of TsOH to yield N,O-diacetyl acyclovir (V). Finally, this compound is deacetylated with NH3, NaOH or pyrrolidine at room temperature, or also with refluxing glycol.

参考文献中间体

合成目标

【1】 Gao, H.; Mitra, A.K.; Synthesis of acyclovir, ganciclovir and their prodrugs: A review. Synthesis 2000, 3, 329.

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)	10352	2-Amino-1,9-dihydro-6H-purin-6-one; Guanine	73-40-5	C₅H₅N₅O	详情	详情
(II)	38958	Guanosine; 2-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one	118-00-3	C₁₀H₁₃N₅O₅	详情	详情
(III)	29161	N-(9-acetyl-6-oxo-6,9-dihydro-1H-purin-2-yl)acetamide; N2,9-Diacetylguanine	3056-33-5	C₉H₉N₅O₃	详情	详情
(IV)	46052	[2-(acetoxy)ethoxy]methyl acetate		C₇H₁₂O₅	详情	详情
(V)	10784	2-[[2-(acetamido)-6-oxo-1,6-dihydro-9H-purin-9-yl]methoxy]ethyl acetate; Acetic acid 2-(2-acetamido-6-oxo-1,6-dihydro-purin-9-ylmethoxy)-ethyl ester	75128-73-3	C₁₂H₁₅N₅O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The intermediate iodopurine (IX) was prepared as follows. Acetylation of guanosine (I) afforded the triacetate ester (II). Subsequent chlorination of (II) to the 6-chloropurine (III) was accomplished by treatment with phosphoryl chloride and N,N-dimethylaniline. Diazotization of (III) with isoamyl nitrite in the presence of CuI furnished the 6-chloro-2-iodopurine (IV). Displacement of the 6-chloro group of (IV) in liquid ammonia with concomitant ammonolysis of the acetate esters gave rise to the 6-amino derivative (V). The dioxolane ketal (VI) was then formed by treatment of (V) with 2,2-dimethoxypropane in the presence of p-toluenesulfonic acid. After oxidation of the primary alcohol of (VI) with alkaline KMnO4 to give (VII), its ketal hydrolysis using 50% formic acid produced the carboxylic acid (VIII). The required N-ethyl amide (IX) was then obtained by esterification with SOCl2/EtOH, followed by treatment with liquid ethylamine.

参考文献中间体

合成目标

【1】 Linden, J.M.; MacDonald, T.; Glover, D.K.; Beller, G.A. (University of Virginia); Induction of pharmacological stress with adenosine receptor agonists. JP 2003502433; WO 0078774 .

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)	38958	Guanosine; 2-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one	118-00-3	C₁₀H₁₃N₅O₅	详情	详情
(II)	38959	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate		C₁₆H₁₉N₅O₈	详情	详情
(III)	22299	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(2-amino-6-chloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate		C₁₆H₁₈ClN₅O₇	详情	详情
(IV)	59471	(2R,3R,4R,5R)-4-(acetyloxy)-2-[(acetyloxy)methyl]-5-(6-chloro-2-iodo-9H-purin-9-yl)tetrahydro-3-furanyl acetate		C₁₆H₁₆ClIN₄O₇	详情	详情
(V)	22396	(2R,3R,4S,5R)-2-(6-amino-2-iodo-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol	35109-88-7	C₁₀H₁₂IN₅O₄	详情	详情
(VI)	22397	[(3aR,4R,6R,6aR)-6-(6-amino-2-iodo-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methanol		C₁₃H₁₆IN₅O₄	详情	详情
(VII)	22398	(3aR,4S,6R,6aR)-6-(6-amino-2-iodo-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carboxylic acid		C₁₃H₁₄IN₅O₅	详情	详情
(VIII)	22399	(2S,3S,4R,5R)-5-(6-amino-2-iodo-9H-purin-9-yl)-3,4-dihydroxytetrahydro-2-furancarboxylic acid		C₁₀H₁₀IN₅O₅	详情	详情
(IX)	22401	(2S,3S,4R,5R)-5-(6-amino-2-iodo-9H-purin-9-yl)-N-ethyl-3,4-dihydroxytetrahydro-2-furancarboxamide		C₁₂H₁₅IN₆O₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Guanosine (I) was protected as the triacetate ester (II) and then chlorinated with POCl3 in the presence of dimethylaniline and tetraethylammonium chloride to give the 6-chloro derivative (III). Diazotization of (III) with tert-butyl nitrite, followed by a modified Sandmeyer reaction provided dichloro purine (IV). Substitution of the 6-chloro of (IV) by 2,2-diphenylethylamine (V) in the presence of diisopropylethylamine in refluxing isopropanol furnished the chloroadenosine derivative (VI), and subsequent removal of the acetate protecting groups of (VI) by hydrolysis with Na2CO3 in aqueous MeOH yielded the adenosine derivative (VII).

参考文献中间体

合成目标

【1】 Gregson, M.; Ayres, B.E.; Ewan, G.B.; Ellis, F.; Knight, J. (Glaxo Wellcome plc); 2,6-Diaminopurine derivs.. EP 0680488; JP 1996505864; US 5925624; WO 9417090 .
【2】 Keeling, S.E.; et al.; The discovery and synthesis of highly potent, A2A receptor agonists. Bioorg Med Chem Lett 2000, 10, 4, 403.

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)	38958	Guanosine; 2-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one	118-00-3	C₁₀H₁₃N₅O₅	详情	详情
(II)	38959	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate		C₁₆H₁₉N₅O₈	详情	详情
(III)	22299	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(2-amino-6-chloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate		C₁₆H₁₈ClN₅O₇	详情	详情
(IV)	25228	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(2,6-dichloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate		C₁₆H₁₆Cl₂N₄O₇	详情	详情
(V)	38962	2,2-diphenylethylamine; 2,2-diphenyl-1-ethanamine	3963-62-0	C₁₄H₁₅N	详情	详情
(VI)	38960	(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-[2-chloro-6-[(2,2-diphenylethyl)amino]-9H-purin-9-yl]tetrahydro-3-furanyl acetate		C₃₀H₃₀ClN₅O₇	详情	详情
(VII)	38961	(2R,3R,4S,5R)-2-[2-chloro-6-[(2,2-diphenylethyl)amino]-9H-purin-9-yl]-5-(hydroxymethyl)tetrahydro-3,4-furandiol		C₂₄H₂₄ClN₅O₄	详情	详情

Extended Information