title: Unusual radical 6-endo cyclization to carbocyclic-ENA and elucidation of its solution conformation by 600 MHz NMR and ab initio calculations.
abstract: 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.
authors.affiliation: Department of Bioorganic Chemistry, Box 581, Biomedical Center, Uppsala University, SE-751 23, Uppsala, Sweden.
authors.forename: Chuanzheng
authors.initials: C
authors.lastname: Zhou
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Plashkevych
authors.forename: Jyoti
authors.initials: J
authors.lastname: Chattopadhyaya
mesh_terms: 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
chemical_list: D000475:Alkenes; D005030:Ethylenes; D005609:Free Radicals; D009696:Nucleic Acids; D012996:Solutions; C036216:ethylene; C117224:1-hexene; D013941:Thymine