Access to oxetane-containing psico-nucleosides from 2-methyleneoxetanes: A role for neighboring group participation?

Yanke Liang, Nathan Hnatiuk, John M. Rowley, Bryan T. Whiting, Geoffrey W. Coates, Paul R. Rablen, Martha Morton, Amy R. Howell

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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 (Figure presented).

Original languageEnglish (US)
Pages (from-to)9962-9974
Number of pages13
JournalJournal of Organic Chemistry
Volume76
Issue number24
DOIs
StatePublished - Dec 16 2011

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Nucleosides
Carbonylation
Stereoselectivity
Epoxy Compounds
Lactones
Substrates
Biological Products
Antiviral Agents
oxetanocin
oxetane
2-methyleneoxetane
penitricin C

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Liang, Y., Hnatiuk, N., Rowley, J. M., Whiting, B. T., Coates, G. W., Rablen, P. R., ... Howell, A. R. (2011). Access to oxetane-containing psico-nucleosides from 2-methyleneoxetanes: A role for neighboring group participation? Journal of Organic Chemistry, 76(24), 9962-9974. https://doi.org/10.1021/jo201565h

Access to oxetane-containing psico-nucleosides from 2-methyleneoxetanes : A role for neighboring group participation? / Liang, Yanke; Hnatiuk, Nathan; Rowley, John M.; Whiting, Bryan T.; Coates, Geoffrey W.; Rablen, Paul R.; Morton, Martha; Howell, Amy R.

In: Journal of Organic Chemistry, Vol. 76, No. 24, 16.12.2011, p. 9962-9974.

Research output: Contribution to journalArticle

Liang, Y, Hnatiuk, N, Rowley, JM, Whiting, BT, Coates, GW, Rablen, PR, Morton, M & Howell, AR 2011, 'Access to oxetane-containing psico-nucleosides from 2-methyleneoxetanes: A role for neighboring group participation?', Journal of Organic Chemistry, vol. 76, no. 24, pp. 9962-9974. https://doi.org/10.1021/jo201565h
Liang, Yanke ; Hnatiuk, Nathan ; Rowley, John M. ; Whiting, Bryan T. ; Coates, Geoffrey W. ; Rablen, Paul R. ; Morton, Martha ; Howell, Amy R. / Access to oxetane-containing psico-nucleosides from 2-methyleneoxetanes : A role for neighboring group participation?. In: Journal of Organic Chemistry. 2011 ; Vol. 76, No. 24. pp. 9962-9974.
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