无溶剂、无催化剂条件下α-腺嘌呤阿拉伯糖苷的合成
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摘要
为了发展有效合成α-腺嘌呤阿拉伯糖苷的方法,以1,2,3,5-四-O-乙酰基-β-D-阿拉伯糖和6-氯嘌呤为原料,在微波辐射和无溶剂、无催化剂条件下反应得到中间体9-α-D-(2',3',5'-三-O-乙酰基)阿拉伯呋喃糖基-6-氯嘌呤,收率85%。该中间体物在Na2CO3催化下脱除乙酰基,然后"一锅"加入饱和的NH3/CH3OH溶液氨解,以90%的收率得到α-腺嘌呤阿拉伯糖苷。关键中间体9-α-D-(2',3',5'-三-O-乙酰基)阿拉伯呋喃糖基-6-氯嘌呤的合成反应规模可以扩大到100 g。类似地合成α-2-氟腺嘌呤阿拉伯糖苷和α-2-氨基腺嘌呤阿拉伯糖苷。
In order to develop the efficient synthesis of α-adenine arabinoside,the key intermediate 9-α-D-( 2',3',5'-tri-O-acetyl)-6-chloropurineside was obtained in 85% yield from the condensation of 6-chloropurine and 1,2,3,5-tetra-O-acetatyl-β-D-arabinose under solvent-and catalyst-free conditions with microwave irradiation. α-Adenine arabinoside was synthesized from the intermediate via deacetylation catalyzed by Na2 CO3,followed by aminolysis in saturated NH3/CH3 OH in one pot. The intermediate was obtained in consist yield even on a 100 g scale. The analogues α-2-fluoroadenine arabinoside and α-2-aminoadenine arabinoside were obtained via similar method.
In order to develop the efficient synthesis of α-adenine arabinoside,the key intermediate 9-α-D-( 2',3',5'-tri-O-acetyl)-6-chloropurineside was obtained in 85% yield from the condensation of 6-chloropurine and 1,2,3,5-tetra-O-acetatyl-β-D-arabinose under solvent-and catalyst-free conditions with microwave irradiation. α-Adenine arabinoside was synthesized from the intermediate via deacetylation catalyzed by Na2 CO3,followed by aminolysis in saturated NH3/CH3 OH in one pot. The intermediate was obtained in consist yield even on a 100 g scale. The analogues α-2-fluoroadenine arabinoside and α-2-aminoadenine arabinoside were obtained via similar method.
引文
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[2] Revankar G R,Huffman J H,Allen L B,et al. Synthesis and Antiviral Activity of Certain 5'-Monophosphates of 9-DArabinofuranosyladenine and 9-D-Arabinofuranosylhypoxanthine[J]. J Med Chem,1975,18(7):721-726.
[3]Thomas H J,Montgomery J A. 7-Glycosylpurines.Ⅱ. Arabinofuranosides of Hypoxanthine and Adenine[J]. J Org Chem,1966,31(5):1413-1416
[4]York J L. Effect of the Structure of the Glycon on the Acid-catalyzed Hydrolysis of Adenine Nucleosides[J]. J Org Chem,1981,46(10):2171-2173.
[5]Lee W W,Benitez A,Goodman L,et al. Potential Anticancer Agent:Synthesis of theβ-Anomer of 9-(D-Arabinofuranosyl)Adenine[J]. J Am Chem Soc,1960,82(10):2648-2649.
[6]Bookser B C,Raffaele N B. High-Throughput Five Minute Microwave Accelerated Glycosylation Approach to the Synthesis of Nucleoside Libraries[J]. J Org Chem,2007,72(1):173-179.
[7]Qu G R,Han S H,Zhang Z G,et al. Microwave-assisted Regioselective Synthesis of Acyclic Nucleosides Through an Alkylating Reaction with 2-Axa-1,4-butanediol Diacetate[J]. Can J Chem,2006,84(5):819-824.
[8]Montgomery J A,Laseter A G,Shortnacy A T,et al. Nucleosides of 2-Azapurines. 7H-Imidazo[4,5-d]-1,2,3-triazines[J]. J Med Chem,1975,18(6):564-567.
[9]Janeba Z,Francom P,Robins M J. Efficient Syntheses of 2-Chloro-2-deoxyadenosine(Cladribine)from 2-Deoxyguanosine[J]. J Org Chem,2003,68(3):989-992.