Sequential ring-closing metathesis and nitrone cycloaddition on glucose-derived substrates: a divergent approach to analogues of spiroannulated carbanucleosides and conformationally locked nucleosides

Sahabuddin, S., Roy, A., Drew, M.G.B., Roy, B.G., Achari, B. and Mandal, S.B. (2006) Sequential ring-closing metathesis and nitrone cycloaddition on glucose-derived substrates: a divergent approach to analogues of spiroannulated carbanucleosides and conformationally locked nucleosides. Journal of Organic Chemistry, 71 (16). pp. 5980-5992. ISSN 0022-3263 doi: 10.1021/jo0606554

Abstract/Summary

The carbohydrate-derived substrate 3-C-allyl-1,2: 5,6-di-O-isopropylidene-alpha-D-allofuranose was judiciously manipulated for preparing suitable synthons, which could be converted to a variety of isoxazolidino-spirocycles and -tricycles through the application of ring-closing metathesis (RCM) and intramolecular nitrone cycloaddition (INC) reactions. Cleavage of the isoxazolidine rings of some of these derivatives by tranfer hydrogenolysis followed by coupling of the generated amino functionalities with 5-amino-4,6-dichloropyrimidine furnished the corresponding chloropyrimidine nucleosides, which were elaborated to spiroannulated carbanucleosides and conformationally locked bicyclo[2.2.1] heptane/ oxa-bicyclo[3.2.1]octane nucleosides. However, use of higher temperature for the cyclization of one of the chloropyrimidines led to the dimethylaminopurine analogue as a sole product, formed via nucleophilic displacement of the chloro group by dimethylamine generated from DMF.