[reaction: see text]. The IMDA reaction of 9 leads with good stereoselectivity to exo-adduct 10b. The functionalized ABC-ring core in 10 is well suited for the convergent synthesis of analogues of himbacine, a naturally occurring M2 selective muscarine receptor antagonist, as illustrated with the further synthesis of the dehydro-derivative 5.

The intramolecular Diels−Alder reaction of bromo-substituted nonatrienoate 24 leads to a mixture of the anti-adducts 25a and 25b, in which the trans-fused lactone 25b, the result of an expected exo-addition, predominates (6.2:1 stereoselectivity). Further introduction of a 2,6-transdisubstituted piperidine ring (26 and 27) via palladium catalyzed cross-coupling reactions (Stille and Sonogashira) affords intermediates that are easily transformed into dehydrohimbacine derivatives 14a, 14b, 15a, and 15b. Binding affinity studies for the muscarine receptors M 1 , M 2 , M 3 , and M 4 show that 15a possesses a 18-fold selectivity for the M 2 relative to the M 1 receptor, but with concomittant loss in affinity compared to the naturally occurring (+)-himbacine (1), a recognized muscarinic receptor antagonist.