SYNTHETIC STUDIES ON QUASSINOIDS - TOTAL SYNTHESIS OF (-)-CHAPARRINONE, (-)-GLAUCARUBOLONE, AND (+)-GLAUCARUBINONE

The total synthesis of (-)-chaparrinone (3), (-)-glaucarubolone (4), and (+)-glaucarubinone (5) is described. The synthesis features an intermolecular Diels-Alder reaction between dienophile 6 and (E)-4-methyl-3,5-hexadienoic acid (17) in 5.0 M lithium perchlorate-ethyl acetate. Diels-Alder adduct 16 is converted via a two-step process into tetracyclic lactone 10. Inversion of configuration at C(9) and installation of a DELTA11,12 olefin in 10 provide tetracyclic lactone 19. Incorporation of the ring C functionality into 19 followed by elaboration of the ring A 1beta-hydroxy-2-oxo-DELTA3,4 olefin unit and removal of the protecting groups on C(1) and C(12) hydroxyl groups affords pre-chaparrinone (41). Upon cleavage of the tert-butyldiphenylsilyl ether present in 41, the resultant hydroxymethyl group spontaneously closes to a C(8),C(11) bridged hemiketal giving rise to (-)-chaparrinone (3). Tetracyclic alcohol 38, an intermediate on the pathway to (-)-chaparrinone, serves as a starting point for the preparation of (-)-glaucarubolone (4). Incorporation of a C(15) hydroxyl group into 38 via tetracyclic dihydropyran 43 followed by introduction of the ring A functionality (cf. 50) and deprotection affords (-)-glaucarubolone (4). The transformation of 50 into (+)-glaucarubinone (5) features a novel reagent, (S)-(-)-5-ethyl-5-methyl-1,3-dioxolane-2,4-dione (54), for direct introduction of a C(15) alpha-hydroxy-alpha-methylbutyrate ester unit.