Abstmc~ Chid synthesis of canadensolide has been achieved by using the Sharpless kinetic resolution of the 2-fnrylcarbmol derivative(l1). followed by its oxidative conversion into the corresponding pyrauoue(l2) as key reactions.
Canadesolide (l), au antibiotic isolated from Penicillin cunadense,* has a unique structnral feature related to avenaciolide (2), isoavenaciolide Q), and ethisolide (4) (Figure ). Its relative stereochemistry has been determined by the total synthesis of its racemate in 1975 by Yoshikoshi and his co-workers.~ Although a number of syntheses of canadensolide have been reported to date,3-5 only two chiral syntheses have been achieved with the use of glucose as a chiral starting materialPJ 0 1 2 3 R=CsH17 4 R=C2HS I 8 9 Scheme 1. Thus the Sharpless kinetic resolution employing titanium tetra-isopropoxide, Ldiisopropyl tartrate, and reti-butyl hydroperoxide was applied to the racemic Sa. Although the absolute configuration of the recovered chiral5a could not be determined at this stage, its enantiomeric excess was only 55% e.e. based on the NMR analysis of the conesponding Masher's ester. In order to improve the optical purity of the resolved starting material in this reaction, the protecting groups of the substituents on the furan ring were exchanged and the kinetic resolution was again attempted. The results obtained were summarized in Table with conversion yields and enantiomeric excesses. Although the Shsrpless kinetic resolution of SC afforded the resolved SC in 44% yield with 62% e.e., such protecting groups were found to be unsuitable in later stage of its further conversion into canadensolide. Table. Kinetic Resolution of 5 Using TBHP, Ti(O'Pr),, and L-(+)-DIPT a substrate 5 slow-reacting enantiomer R' RZ TBHP (equiv.) yield (%)b e.e.( %)' a MOM TBS 2.0 32 55 b MOM SEM 3.0 54 31 C TBS AC 0.7 44 62 ' The reaction was cmied out by using TBHP, Ti(O'Pr)d (1.0 equiv.), and L-(+)-DIPT (1.2 cquiv.) in CH$lz at -2YC in the presence of 3A molecular sieves. b Isolated yields based on racmic 5. ' Determined by 'H NMR analysis of the corresponding MTPA ester.
Since all the attempts for the Sharpless kinetic resolution of trisubstituted 2-furylcarbmols gave the unsatisfactory results in terms of optical purity, we decided to introduce the exo-methylene function of the "I-