Unusual radical 6-endo cyclization to carbocyclic-ENA and elucidation of its solution conformation by 600 MHz NMR and ab initio calculations.
In our previous paper (J. Am. Chem. Soc., 2007, 129, 8362), we reported the synthesis of 7-Me-Carba-LNA and 8-Me-Carba-ENA thymidine through 5-hexenyl or 6-heptenyl radical cyclization. Both 5-hexenyl and 6-heptenyl radical cyclized exclusively in the exo form, giving unwanted exocyclic C7-methyl group. In the present study, we showed that the regioselectivity of the 5-hexenyl radical cyclization could be favorably tuned by introduction of a hydroxyl group to the olefinic double bond, yielding about 9% of the 6-endo cyclization product. Possible pathways to give 6-endo cyclization product 9 compared to the intermediates responsible to give the 5-exo cyclization product 5 has been discussed. Based on this unique 6-endo cyclization strategy, a carbocyclic ENA modified thymidine (carba-ENA) has been successfully synthesized, which also enabled us to perform its full solution conformation analysis by using NMR (1H at 600 MHz) observables for the first time.
Zhou
Chuanzheng
C
Department of Bioorganic Chemistry, Box 581, Biomedical Center, Uppsala University, SE-751 23, Uppsala, Sweden.
Plashkevych
Oleksandr
O
Chattopadhyaya
Jyoti
J
D000475:Alkenes / Q000737:chemistry; D003500:Cyclization; D005030:Ethylenes / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation; D009696:Nucleic Acids / Q000737:chemistry*; D011789:Quantum Theory; D012996:Solutions; D013941:Thymine / Q000737:chemistry
D000475:Alkenes; D005030:Ethylenes; D005609:Free Radicals; D009696:Nucleic Acids; D012996:Solutions; C036216:ethylene; C117224:1-hexene; D013941:Thymine