This paper reports a retrosynthetic analysis that led to the conception of a synthetic strategy for the construction of ryanodol(2). The preparation of a key diene, i.e., spirolactone dienone 47 (19 + 31 -, 33 + 48 + 49 + 52 + 47). and its Diels-Alder reaction with methyl vinyl ketone are reported.Key words: strategy, synthesis, ryanodol, diterpene.PIERRE DESLONGCHAMPS, A N D R~ B~L A N G E R , DANIEL J. F. BERNEY, HANS-JUERG BORSCHBERG, ROBERT BROUSSEAU, ALAIN DOUTHEAU, ROBERT DURAND, HAJIME KATAYAMA, RICHARD LAPALME, DOMINIQUE M. LETURC, CHUN-CHEN LIAO, FREDERICK N. MACLACHLAN, JEAN-PIERRE MAFFRAND, FABRIZIO MARAZZA, ROBERT MARTINO, CLAUDE MOREAU, LUC RUEST, LOUISELLE SAINT-LAURENT, ROGER SAINTONGE et PIERRE SOUCY Can. J . Chem. 68, 115 (1990).On rapporte l'analyse rCtrosynthCtique qui a conduit a la conception d'une strattgie menant a la synthkse du ryanodol(2). On dkcrit la synthkse du dikne-clC, la spirolactone diCnone 47 (19+ 31 + 33+ 48+ 4 9 4 52-47), et sa rCaction de Diels-Alder avec la mtthylvinylcCtone.Mots cles : stratkgie, synthkse, ryanodol, diterpkne.Ryanodine (I), a natural product isolated from Ryania speciosa Vahl, is the ester of pyrrole a-carboxylic acid and the complex diterpene (+)-ryanodol(2) (1) (Scheme 1). The structure of ryanodine including its absolute configuration was elucidated by Wiesner et al. at the University of New Brunswick (2). This work constitutes one of the most brilliant accomplishments in structure elucidation using chemical degradation, and remains a classic piece. The X-ray analysis of thep-bromobenzyl ether 3 of ryanodol was carried out by Srivastava and Przybylska (3). The original assignment of Wiesner was confirmed except for a minor point; the X-ray analysis revealed that the configuration of the isopropyl and tertiary hydroxyl groups at C2 had to be reversed and is as indicated in structures 1-3. ' We completed a total synthesis of (+)-ryanodol in 1979. This work was published in a preliminary form (4) and we now wish to report our investigation in detail. In Part I (this paper), we explain our general synthetic strategy (5, 6) and describe the preliminary experiments leading to the discovery of a very convenient unsymmetrical diene, which was needed for the construction of a key tricyclic intermediate via a Diels-Alder cycloaddition. Parts 11-IV describe the remaining work (see accompanying papers).
General strategyRyanodol, a C20H3208 compound, is a pentacyclic diterpene, which has a ring skeleton consisting of 14 carbons and one oxygen atom. Thus, four rings (A, B, C, and E) are carbocyclic whereas the fifth one (ring D) contains an oxygen atom. There is an isopropyl group as well as a tertiary methyl group in ring A, a tertiary methyl group in ring B, and an equatorially oriented secondary methyl group in ring C. In addition, there are five tertiary hydroxyl groups, one of which is part of a hemi-ketal function at one of the junctions of ring D and ring E (cf. C15), and two secondary hydroxyl groups, one in ring A (a-oriented) and one in ring C (a-oriented...