[Reaction of 3-hydroxy-dihydrosantonin with TsOH. A formal synthesis of dihydrocotunolide].
In connection with our another project a relatively large quantity of 5 was required. We, therefore, investigated the reaction of 3 with TsOH; this gave a diene mixture 7a, 7b, 6 and 5 in a ratio of 8:2:4:1. Almost the same 8:2:1 "equilibrium mixture" of the dienes 7a, 7b and 5 was also obtained when the purified samples of 5 and 7a were independently treated with TsOH under the same conditions. The above results suggest that the dienes might be produced in the following way; beta-elimination of H2O from 3 gives a homoannular diene 5. The protonation to the more electron-rich tetrasubstituted C4-C5 double bond of 5 from the less hindered alpha-side followed by the isomerization of the double bond gives 7a. 7b is formed via 7a and/or 5 by the double bond isomerizations. On the other hand, 6 is formed by concerted elimination of H2O between C3-OH and C6-H. As a result of these studies, the synthetic precursor of dihydrocostunolide 7b which was already prepared by Corey in 6 steps (ca. 7%) from santonin was synthesized in 3 steps (ca. 6%) from the latter.
Kawamata
T
T
Pharmaceutical Institute, School of Medicine, Keio University, Tokyo, Japan.
Takenaka
K
K
Tsuji
T
T
D000962:Antimalarials / Q000138:chemical synthesis*; D001557:Benzenesulfonates; D055598:Chemical Phenomena; D002621:Chemistry; D012500:Santonin / Q000031:analogs & derivatives*; D012717:Sesquiterpenes / Q000138:chemical synthesis*
C104087:3-hydroxydihydrosantonin; D000962:Antimalarials; D001557:Benzenesulfonates; D012717:Sesquiterpenes; C104088:dihydrocotunolide; D012500:Santonin; C029501:4-toluenesulfonic acid