Modular Synthesis of Constrained Ethyl (cEt) Purine and Pyrimidine Nucleosides

Journal of Organic Chemistry

Volumn 80, Issue 10, 2015, Pages 5337-5343

  Blade, Helen ^a   Bradley, Derek ^a   Diorazio, Louis ^a   Evans, Timothy ^a   Hayter, Barry R ^a   Howell, Gareth P ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AROMATIC COMPOUNDS;

CHEMICAL EQUATIONS; COMPLEX CLASS; DIACETONE GLUCOSE; FUNCTIONALIZED; MODULAR SYNTHESIS; PROTECTING GROUP; PYRIMIDINE NUCLEOSIDES; SCALABLE APPROACH;

BIOMOLECULES;

ACETONYLACETONE; NUCLEOSIDE DERIVATIVE; PURINE DERIVATIVE; PYRIMIDINE DERIVATIVE; NUCLEOSIDE; PRODRUG; PURINE NUCLEOSIDE; PYRIMIDINE NUCLEOSIDE;

ALDOL REACTION; ARTICLE; CIS ISOMER; CRYSTALLIZATION; CYCLIZATION; GLYCOSIDATION; HYDROGENATION; MOLECULAR WEIGHT; OXIDATION; SOLVOLYSIS; STEREOCHEMISTRY; STEREOISOMERISM; SYNTHESIS; TRANS ISOMER; X RAY ANALYSIS; CHEMICAL STRUCTURE; CHEMISTRY;

MOLECULAR STRUCTURE; NUCLEOSIDES; PRODRUGS; PURINE NUCLEOSIDES; PYRIMIDINE NUCLEOSIDES;

EID: 84929591031     PISSN: 00223263     EISSN: 15206904     Source Type: Journal    
DOI: 10.1021/acs.joc.5b00607     Document Type: Article

References (22)

1. Tamm, I.; Dörken, B.; Hartmann, G. Lancet 2001, 358, 489 - 497
2. Seth, P. P.; Vasques, G.; Allerson, C. A.; Berdeja, A.; Gaus, H.; Kinberger, G. A.; Prakash, T. P.; Migawa, M. T.; Bhat, B.; Swayze, E. E. J. Org. Chem. 2010, 75, 1569 - 1581
3. Gibson, N. W. J. Publ.-R. Coll. Physicians Edinburgh 2014, 44, 196
4. Hong, D.; Kim, Y.; Younes, A.; Nemunaitis, J.; Fowler, N.; Hsu, J.; Zhou, T.; Fayad, L.; Zhang, N.; Piha-Paul, S.; Woessner, R.; Nadella, M. V.; Lawson, D.; Reimer, C.; Jo, M.; Schmidt, J.; Xiao, X.; Greenlee, S.; Hung, G.; Yamashita, M.; Blakey, D. C.; Monia, B. P.; Macleod, A. R.; Kurzrock, R. Cancer Res. 2014, 74, LB-227
5. Betson, M.; Allanson, N.; Wainwright, P. Org. Biomol. Chem. 2014, 12, 9291 - 9306
6. Salinas, J. C.; Migawa, M. T.; Merner, B. L.; Hanessian, S. J. Org. Chem. 2014, 79, 11651 - 11660
7. Seth, P. P.; Yu, J.; Allerson, C. R.; Berdeja, A.; Swayze, E. E. Bioorg. Med. Chem. Lett. 2011, 21, 1122 - 1125
8. Seth, P. P.; Siwkowski, A.; Allerson, C. R.; Vasquez, G.; Lee, S.; Prakash, T. P.; Kinberger, G.; Migawa, M. T.; Gaus, H.; Bhat, B.; Swayze, E. E. Nucleic Acids Symp. Ser. 2008, 52, 553 - 554
9. Vasquez, G. Patent WO 2009/143369 A2, 2009.
10. Swayze, E. E.; Seth, P. P. Patent WO 2007/090071 A2, 2007.
11. The 12 steps required to synthesize common intermediate 4 are counted only once.
12. Defects in the modular sugar core undergo net amplification upon conversion into oligonucleotide chains. For example, four nucleosides (A, G, C, and U) derived from a common sugar (S) building block containing x% of an anomalous sugar impurity (S∗) will each contain x% of the related nucleoside impurity (A∗, G∗, C∗, and U∗, respectively). When multiple (n) nucleosides are coupled into an oligonucleotide sequence, there will be a family of oligonucleotide impurities containing one (unspecified) anomalous nucleoside (A-G-C⋯)∗ present at a level of nx%. The exact identity, as well as the toxicology and efficacy, of specific impurities in this family requires careful consideration.
13. Merino, P. Chemical Synthesis of Nucleoside Analogues; Wiley: New York, 2013.
14. Butters, M.; Catterick, D.; Craig, A.; Curzons, A.; Dale, D.; Gillmore, A.; Green, S. P.; Marziano, I.; Sherlock, J.-P.; White, W. Chem. Rev. 2006, 106, 3002 - 3027
15. Koshkin, A. A.; Singh, S. K.; Nielsen, P.; Rajwanshi, V. K.; Kumar, R.; Meldgaard, M.; Olsen, C. E.; Wengel, J. Tetrahedron 1998, 54, 3607 - 3630
16. Enderlin, G.; Nielsen, P. J. Org. Chem. 2008, 73, 6891 - 6894
17. Turks, M.; Rodins, V.; Rolava, E.; Ostrovskis, P.; Belyakov, S. Carbohydr. Res. 2013, 375, 5 - 15
18. Fukuyama, K.; Ohrui, H.; Kuwahara, S. Org. Lett. 2015, 17, 828 - 831
19. Szeja, W. Carbohydr. Res. 1986, 158, 245 - 248
20. Vorbruggen, H.; Ruh-Pohlenz, C. Org. React. (Hoboken, NJ, U.S.) 2000, 55
21. Cipolla, L.; Airoldi, C.; Bini, D.; Gregori, M.; Marcelo, F.; Jiménez-Barbero, J.; Nicotra, F. Eur. J. Org. Chem. 2011, 128 - 136
22. In a manner consistent with the step-counting approach used previously (Scheme 1 and ref 11), the eight steps to common intermediate 11 are counted only once.