Synthesis of furo[2,3-c]pyran-β-d-nucleosides by radical-cyclization & their conformational analysis by 500 mhz 1h-nmr spectroscopy

Free-radical, generated from the 3*-phenylseleno nucleosides as the radical precursors 2 - 5. was ejiciently trapped intramolecularly by an olefin or alkyne Jtntion anchored from the 5*-end by an ether function to give various (3.4.0)-cis-fusedfuro(23-clpyrans 6 - 9 (16-348) along with some reduced products (~10%). Similar intramolecular radical trappingreaction with S-0-a&ester-linkedf raa%cal precursor IO - 12. under an idendcal reaction condition, gave (3.4.0)-cis-fused Glactones 13 - 15 in IO-5346 yields without any trace of reduced products. The synthesis of (3.4.0)-cis-fused furo-pyrans 6 - 9 from I-oxod-heptenyl radical formed from the precursor 2 - 5 and the transformations of 10 - I2 to Glactones I3 - 15. respectively. constitute first example of intramolecular 6-exe radical cyclization reaction involving the nucleophilic attack of endocyclic ring-radical to the electron-deficient exocyclic unsaturated chain. Smooth conversion of Glactones 14 and IS to the ring-opened C-branched erythro derivatives 16 (95%) and 17 (94%). respectively, upon treatment with diluted aqueous ammonia have provided a new methodology for diastereospecific synthesis of 3-C-branched nucleosi&s throughfree-r&cat cyclisation and ring-opentng sequence. The structures offuro(23-clpyrans 6 - 9 and Glactones 13 - IS have been firmly established by &tailed ID differential nOe experiments. Subsequently, w have also analyzed all 3JBB coupling constants at 500 MHz at 0 9 20" and 40 "c to estimate all et&cyclic dihedral angles using the Karplus-Altona algorithm. Temperature-independent 3JBB clearly show thatfiuo(2,3-clpyrans 6 - 9 and Glactones 13 - IS have rigid conformations. Construction of molecular models using the en&cyclic torsions of the pentose wdt and various dihedral angles of the pyran or Glactone unit shows that the pyran ring in (3.4.0)-cis-furedfwo-pyrans 6 - 9 are in chair conformation and the pentofuranose ring is in North conformation (Figs. IA & 1B). while the S-lactone ring in (3.4.0)-cis-fused Glactones 13 - I5 are in boat conformation and the pentofuranose ring is locked in South conformation (Figs. 1C & ID). The C*-alkyl substituents in the sin-membered ring in both fwo(23-clpyrans 6 - 9 and in Glactones I3 - 15 are oriented however in an equatorial position. A comparison.of interproton distances obtained from molecular models (Fig. IA - D).. based on .'JRB coupling constants, with those obtainedfrom volumes and intensities of nOe and roe crosspeaks in the NOESY and ROESY spectra supports the molecular models shown in Fig. 1.