Citation: Sun Zhidong, Zhu Yunlong, Huang Haiyang, Song Xianrong, Xiao Qiang. Studies on the Total Synthesis of iso-L-Cystidine[J]. Chinese Journal of Organic Chemistry, ;2016, 36(11): 2729-2734. doi: 10.6023/cjoc201605036 shu

Studies on the Total Synthesis of iso-L-Cystidine

1.
Key Laboratory of Organic Chemistry in Jiangxi Province, Institute of Organic Chemistry, Jiangxi Science & Technology Normal University, Nanchang 330013

Corresponding author: Xiao Qiang, xiaoqiang@tsinghua.org.cn
Received Date: 19 May 2016
Revised Date: 4 July 2016

Fund Project: National Natural Science Foundation of China 21462019the Bureau of Science & Technology of Jiangxi Province 20143ACB20012the New Century Excellent Talents in University 11-1000

Figures(3)

In order to systematic study the biological effects of isonucleoside incorporated oligonucleotides, an efficient synthetic process for iso-L-cystidine was investigated in present paper. Using L-ribose as starting material, iso-L-cystidine was obtained in 9 steps and 28.5% overall yield. The key step was the regioselective nucleophilic substitution of 5-O-triphenylmethane-2, 3-O-cyclic sulfate with uracil. After extensive optimization, it was found that using cesium carbonate as base can improve significantly the N-1 glycosidic bond formation and reduce the side reactions. At the same time, a N-1, N-3 doublic 1-deoxyribose substituted iso-L-uridine was identified for the first time. The present reported synthetic process has the merits of mild reaction conditions, easy purified intermediates and high overall yield, which could be used as a general synthetic approach for the preparation other related isonucleoside.
- nucleosides,
- total synthesis,
- glycosidation,
- nucleophilic substitution,
- isonucleosides
1. [1]
  Jordheim, L. P.; Durantel, D.; Zoulim, F.; Dumontet, C. Nat. Rev. Drug Discovery 2013, 12, 447.
  (b) Zhou, X.-X.; Littler, E. Curr. Top. Med. Chem. 2006, 6, 851.
  (c) Huryn, D. M.; Okabe, M. Chem. Rev. 1992, 92, 1745.
  (d) Wu, Y.-W.; Jiang, Y.-Y.; Fu, H.; Yang, J.; Zhao, Y.-F. Chin. J. Org. Chem. 2003, 23, 1091 (in Chinese). (吴耀文, 蒋宇扬, 付华, 杨杰, 赵玉芬, 有机化学, 2003, 23, 1091.)
  (e) Fan, X.-S.; Zhang, X.-Y.; Wang, X.; Qu, G.-R. Chin. J. Org. Chem. 2008, 28, 1888 (in Chinese). (范学森, 张新迎, 王霞, 渠桂荣, 有机化学, 2008, 28, 1888.)
2. [2]
  Montgomery, J. A.; Clayton, S. D.; Thomas, H. J. J. Org. Chem. 1975, 40, 1923.
  (b) Montgomery, J. A.; Thomas, H. J. J. Org. Chem. 1978, 43, 541.
3. [3]
  Bloch, A.; Robins, M. J.; McCarthy, J. R. J. Med. Chem. 1967, 10, 908.
  (b) Nair, V.; Jahnke, T. S. Antimicrob. Agents Chemother. 1995, 39, 1017.
4. [4]
  Nair, V.; Piotrowska, D. G.; Okello, M.; Vadakkan, J. Nucleos Nucleot. Nucl. 2007, 26, 687.
  (b) Chun, B. K.; Vadakkan, J. J.; Nair, V. Nucleosides, Nucleotides, Nucleic Acid 2005, 24, 725.
  (c) Chi, G. C.; Neamati, N.; Nair, V. Bioorg. Med. Chem. Lett. 2004, 14, 4815.
  (d) Tian, X.-B.; Zhang, L.; Min, J.-M.; Zhang, L.-H.; Lu, Y.; Jiang, R.-W.; Zheng, Q.-T. Chem. Res. Chin. Univ. 2001, 17, 178.
  (e) Song, Y.; Yang, R.; Ding, H.; Sun, Q.; Xiao, Q.; Ju, Y. Synthesis-Stuttgart 2011, 1213.
5. [5]
  Cai, B.; Yang, X.; Sun, L.; Fan, X.; Li, L.; Jin, H.; Wu, Y.; Guan, Z.; Zhang, L.; Zhang, L.; Yang, Z. Org. Biomol. Chem. 2014, 12, 8866. doi: 10.1039/C4OB01525H
6. [6]
  Huang, Y.; Chen, Z.; Chen, Y.; Zhang, H.; Zhang, Y.; Zhao, Y.; Yang, Z.; Zhang, L. Bioconjugate Chem. 2013, 24, 951. doi: 10.1021/bc300642u
7. [7]
  Okello, M, Nair, V. Chem. Synth. Nucleoside Analogues 2013, 317.
8. [8]
  Purdy, D. F.; Zintek, L. B.; Nair, V. Nucleosides Nucleotides 1994, 13, 109. doi: 10.1080/15257779408013230
9. [9]
  Bennek, J. A.; Gray, G. R. J. Org. Chem. 1987, 52, 892. doi: 10.1021/jo00381a030
10. [10]
  CCDC 1474741 (5) contain the supplementary crystallographic data for this paper.
11. [11]
  Dijkstra, G.; Kruizinga, W. H.; Kellogg, R. M. J. Org. Chem. 1987, 52, 4230.
  (b) Ostrowicki, A.; Koepp, E.; Vögtle, F. Macrocycles 1992, 37.
  (c) Galli, C. Org. Prep. Proced. Int. 1992, 24, 285.
  (d) Huang, H.-Y.; Sun, Z.-D.; Gong, Z.-W.; Xiao, Q.; Chen, X. Adv. Mater. Res. 2014, 997, 193.
12. [12]
  Freeman, G. A.; Selleseth, D. W.; Rideout, J. L.; Harvey, R. J. Nucleosides Nucleotides Nucleic Acid 2000, 19, 155.
  (b) Verheggen, I.; Aerschot, A. V.; Toppet, S.; Snoeck, R.; Janssen, G.; Balzarini, J.; Clercq, E. D.; Herdewijn, P. J. Med. Chem., 1993, 36, 2033.
13. [13]
  Blackburn, M.; Gait, M.; Loakes, D. Nucleic Acids in Chemistry and Biology, Ed.:Williams, D., Cambridge, UK, 2006.
14. [14]
  Yu, H.-W.; Zhang, L.-R.; Zhou, J.-C.; Ma, L.-T.; Zhang, L.-H. Bioorg. Med. Chem. 1996, 4, 609. doi: 10.1016/0968-0896(96)00048-X
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沈阳化工大学材料科学与工程学院沈阳 110142