A new methodology for the synthesis of carbofuranoses and related carbanucleosides

Carbocyclic nucleosides (carbanucleosides) are mimetics of natural nucleosides and have been the subject of intense research in recent years. Many analogues of carbanucleosides have exhibited potent anti-viral and anti-tumour properties. Thus, there is a continuing interest for synthetic methodologies to access carbanucleosides analogues in enantiomerically pure form. (Fig. 14249) This thesis describes the development of a novel approach for the enantiospecific synthesis of carbafuranose analogues and the conversion of the synthesised carbafuranoses into the corresponding carbanucleosides. The core of the methodology concerns the construction of the cyclopentane moiety of the carbanucleoside by a Brook rearrangement-mediated domino carbacyclisation. Hence, the coupling of a lithio-tert-butyldimethyl-1,3-dithiane linchpin with chiral symmetric bis-epoxide substrates led to highly functionalised spiro-thioketals which could be converted to a range of carbafuranose analogues in straightforward transformations. The symmetric bis-epoxide building blocks were synthesised from arabitol, which is available in both enantiomeric forms. The hetereonucleobase of the carbanucleoside was then introduced to the suitably protected cycloalkanols to afford the corresponding carbanucleoside targets.