The use of cyclopentenones in the synthesis of novel carbocycles

• Main Author: Burke, Mark Richard
• Published: Queen's University Belfast 1996
• Subjects: 547.6
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.486045

4-Substituted cyclopentenones are key intermediates in the preparation of an array of highly functionalised cyclopentanes including most importantly in the project, carbocyclic nucleosides which display interesting biological activity. With the discovery that one stereoisomer exhibits generally more biological activity than the opposite stereoisomer and the escalating demand for new drugs to be enantiomerically pure, has led to the principal use ofenzymes in the development of routes to chiral carbocyclic nucleosides. The 1,4-diacetate was prepared via 3,4-diacetoh.)'cyclopentene using a modified method proposed by Deardorff and Mylesl . Following the limited success of this preparation, an alternative approach was adopted. An alternative approach to 1,4diacetoxycyclopentene used the photoaddition of singlet Oh.')'gen to the substrate cyclopentadiene, followed by protection. Elaboration ofthe 1,4-diacetate was attempted to afford various cyclopentenones via asymmetric hydrolysis, followed a photoaddition of methanol to the enone and a Mitsunobu reaction to afford the desired carbocyclic nucleoside. Selective deprotection of the silyl protecting group furnished a carbocyclic nucleoside analogue, which could be used for further elaboration to an array ofinteresting carbocyclic compounds. E),'olution ofthe project led to the synthesis ofseveral chir~l 4-alkyl-8-alkoxy-2-oxa-3aza- bicydo[3.3 .O]oct~3-en-6-Qnes. Further expansion of the tert-butyldimethylsilyl protected bicyclo-Qctenone to the bis-isoxazoline and symmetrical hydroxymethyl cyclopentanone diol were investigated with an array of chemical manipulations.