Journal of Medicinal Chemistry p. 2787 - 2797 (1991)
Update date:2022-07-29
Topics:
Peterson, Mark L.
Vince, Robert
The synthesis of several novel carbocyclic purine nucleosides that incorporate a nitrogen in place of carbon 3 of the cyclopentyl moiety are described.These analogues are all derived from the key stereochemically defined intermediate N-(tert-butoxycarbonyl)-O-<(4-methoxyphenyl)diphenylmethyl>-trans-4-hydroxy-D-prolinol (19), which was accessible in 61.1percent overall yield for a five-step sequence starting from cis-4-hydroxy-D-proline.The heterocyclic bases, 6-chloropurine and 2-amino-6-chloropurine, are efficiently introduced onto the pyrrolidine ring via a Mitsunobu-type coupling procedure with triphenylphosphine and diethyl azodicarboxylate.Standard transformations and removal of protecting groups gave the cis-adenine (26), hypoxanthine (27), 2,6-diaminopurine (28), and guanine (29) D-prolinol derivatives.In addition, a related sequence from trans-4-hydroxy-L-proline provided the enantiomeric L-prolinol guanine derivative (36).Lastly, the 6-(dimethylamino)purine analogue, 37, was coupled to N-(benzyloxycarbonyl)-p-methoxy-L-phenylalanine to provide, after deprotection, the novel puromycin-like analogue 39.The analogues 26-29, 36, and 39 were all evaluated for antitumor and, except for 39, for antiviral activity.These compounds failed to appreciably inhibit the growth of P388 mouse leukemia cells in vitro at concentrations up to 100 μg/mL.In addition, they did not exhibit noticeable activity against the human immunodeficiency virus or herpes simplex virus type 1 at concentrations as high as 100 μM.The adenine analogue, 26, did, however, prove to be a substrate for adenosine deaminase.It possessed an affinity for the enzyme only 50percent less than that of adenosine with a Ki = 85 μM.
View MoreJiangyin Tenghua Import&Export Co.,Ltd.
Contact:+86-510-86263875
Address:Room 402-B,9 Yanling Road, Jiangyin,Jiangsu, China
Contact:+86-27-87204219, +86-27-87215023
Address:2402, HuiGu Space-time Building, 8 Forest Road, East Lake Hi-Tech Development Zone
Hangzhou Maytime Bio-Tech Co.,Ltd.
website:http://www.maytime.com.cn
Contact:+86-571-88925295 88920965
Address:NO.2-1701 Ganghui Central Ningwei Street, Xiaoshan Hangzhou Zhejiang China
Beijing Huikang Boyuan Chemical Tech Co.,LTD
Contact:+86-10-68862197
Address:No.7 Haiying Road,Science City,Fengtai District,Beijing,China
Ceresking Ecology & Technology co.,ltd
Contact:86 22 66218397
Address:Room 1613, Zheshang Mansion, No. 1988, Yingbin Avenue, Binhai New District, Tianjin,China.
Doi:10.1002/jhet.631
(2011)Doi:10.1039/c5gc01930c
(2016)Doi:10.1021/acs.inorgchem.9b02608
(2019)Doi:10.1002/anie.201104870
(2011)Doi:10.1039/c1dt11279a
(2012)Doi:10.1007/s11164-011-0426-4
(2012)