Abstract

Free-radical, generated from the 3'-phenylseleno nucleosides as the radical precursors 2-5, was efficiently trapped intramolecularly by an olefin or alkyne funtion anchored from the 5'-end by an ether function to give various [3.4.0]-cis-fused furo[2,3-c]pyrans 6-9 (16-34%) along with some reduced products (< 10%). Similar intramolecular radical trapping reaction with 5'-O-alpha,beta-ester-linked free radical precursor 10-12, under an identical reaction condition, gave [3.4.0]-cis-fused delta-lactones 13-15 in 10-53% yields without any trace of reduced products. The synthesis of [3.4.0]-cis-fused furo-pyrans 6-9 from 4-oxo-6-heptenyl radical formed from the precursor 2-5 and the transformations of 10-12 to delta-lactones 13-15, respectively, constitute first example of intramolecular 6-exo radical cyclization reaction involving the nucleophilic attack of endocyclic ring-radical to the electron-deficient exocyclic unsaturated chain. Smooth conversion of delta-lactones 14 and 15 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 nucleosides through free-radical cyclization and ring-opening sequence. The structures of furo[2,3-c]pyrans 6-9 and delta-lactones 13-15 have been firmly established by detailed 1D differential nOe experiments. Subsequently, we have also analyzed all 3J(HH) coupling constants at 500 MHz at 0-degrees, 20-degrees and 40-degrees-C to estimate all endocyclic dihedral angles using the Karplus-Altona algorithm. Temperature-independent 3J(HH) clearly show that furo[2,3-c]pyrans 6-9 and delta-lactones 13-15 have rigid conformations. Construction of molecular models using the endocyclic torsions of the pentose unit and various dihedral angles of the pyran of delta-lactone unit shows that the pyran ring in [3.4.0]-cis-fused furo-pyrans 6-9 are in chair conformation and the pentofuranose ring is in North conformation (Figs. 1A & 1B), while the delta-lactone ring in [3.4.0]-cis-fused delta-lactones 13-15 are in boat conformation and the pentofuranose ring is locked in South conformation (Figs. 1C & ID). The C*-alkyl substituents in the six-membered ring in both furo[2,3-c]pyrans 6-9 and in delta-lactones 13-15 are oriented however in an equatorial position. A comparison of interproton distances obtained from molecular models (Fig. 1A - D), based on 3J(HH) coupling constants, with those obtained from volumes and intensities of nOe and rOe crosspeaks in the NOESY and ROESY spectra supports the molecular models shown in Fig. 1.

Published in

Tetrahedron
1991, Volume: 47, number: 46, pages: 9675-9690
Publisher: PERGAMON-ELSEVIER SCIENCE LTD

UKÄ Subject classification

Organic Chemistry


Publication identifier

DOI: https://doi.org/10.1016/S0040-4020(01)91032-4

Permanent link to this page (URI)

https://res.slu.se/id/publ/83895