Access to oxetane-containing psico-nucleosides from 2-methyleneoxetanes: a role for neighboring group participation?
The first psico-oxetanocin analogue of the powerful antiviral natural product, oxetanocin A, has been readily synthesized from cis-2-butene-1,4-diol. Key 2-methyleneoxetane precursors were derived from β-lactones prepared by the carbonylation of epoxides. F(+)-mediated nucleobase incorporation provided the corresponding nucleosides in good yield but with low diastereoselectivity. Surprisingly, attempted exploitation of anchimeric assistance to increase the selectivity was not fruitful. A range of 2-methyleneoxetane and related 2-methylenetetrahydrofuran substrates was prepared to explore the basis for this. With one exception, these substrates also showed little stereoselectivity in nucleobase incorporation. Computational studies were undertaken to examine if neighboring group participation involving fused [4.2.0] or [4.3.0] intermediates is favorable.
Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269-3060, USA.
Yanke
Y
Liang
Nathan
N
Hnatiuk
John M
JM
Rowley
Bryan T
BT
Whiting
Geoffrey W
GW
Coates
Paul R
PR
Rablen
Martha
M
Morton
Amy R
AR
Howell
D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D000998:Antiviral Agents / Q000138:chemical synthesis*; D002072:Butylene Glycols / Q000737:chemistry; D004852:Epoxy Compounds / Q000737:chemistry*; D004988:Ethers, Cyclic / Q000737:chemistry*; D005461:Fluorine / Q000737:chemistry; D005663:Furans / Q000138:chemical synthesis; D006801:Humans; D007783:Lactones / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry*; D013237:Stereoisomerism
C527427:2-methyleneoxetane; D000998:Antiviral Agents; D002072:Butylene Glycols; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D005663:Furans; D007783:Lactones; D009705:Nucleosides; C051061:oxetanocin; C042544:penitricin C; D005461:Fluorine; D000225:Adenine