Kawamata T, Takenaka K, Tsuji T
Pharmaceutical Institute, School of Medicine, Keio University, Tokyo, Japan.
Yakugaku Zasshi. 1996 Sep;116(9):748-52. doi: 10.1248/yakushi1947.116.9_748.
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.
在我们的另一个项目中，需要相对大量的5。因此，我们研究了3与对甲苯磺酸（TsOH）的反应；这得到了二烯混合物7a、7b、6和5，其比例为8:2:4:1。当5和7a的纯化样品在相同条件下分别用TsOH处理时，也得到了几乎相同的二烯7a、7b和5的8:2:1“平衡混合物”。上述结果表明，二烯可能以下列方式生成；3的β-消除水得到一个同环二烯5。从空间位阻较小的α-侧对5中电子密度较高的四取代C4-C5双键进行质子化，随后双键异构化得到7a。7b通过7a和/或5的双键异构化形成。另一方面，6是由C3-OH和C6-H之间的水协同消除形成的。这些研究的结果是，二氢木香内酯7b的合成前体，Corey已经从山道年通过6步反应（约7%产率）制备得到，现在从山道年通过3步反应（约6%产率）合成得到。
