Toró András, Deslongchamps Pierre
Laboratoire de Synthèse Organique, Institut de Pharmacologie, Université de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada.
J Org Chem. 2003 Sep 5;68(18):6847-52. doi: 10.1021/jo034123o.
(+)-anhydrochatancin was synthesized while attempting an enantioselective total synthesis of (+)-chatancin. The presented route constitutes the furanophane approach, one of the two ways of proposed biosynthesis which may involve transannular Diels-Alder (TADA) reaction to link this diterpene biogenetically to the furanocembranoids. Highlights of the synthetic work include the assembly of chiral, acyclic, trisubstituted furan 28 via a coupling of aldehyde 10 and dilithiofuroic acid 11, a macrocyclization to furanophane 29E via ring-closing metathesis, a TADA reaction to reach tetracyclic intermediate 4, and a hydride shift mediated oxygen transposition as a final rearrangement to the target. Unfortunately, the strongly acidic condition required for the last step allows only the isolation of anhydrochatancin 30 due to the acid sensitivity of chatancin 1.
在尝试对（+）-查坦辛进行对映选择性全合成时，合成了（+）-脱水查坦辛。所展示的路线构成了呋喃环烷方法，这是所提出的生物合成的两种方式之一，其中可能涉及分子内狄尔斯-阿尔德（TADA）反应，从而将这种二萜生物合成地连接到呋喃类西松烷。合成工作的亮点包括通过醛10和二锂呋喃甲酸11的偶联组装手性、无环、三取代呋喃28，通过闭环复分解反应大环化至呋喃环烷29E，通过TADA反应得到四环中间体4，以及通过氢化物转移介导的氧迁移作为最终重排得到目标产物。不幸的是，由于查坦辛1对酸敏感，最后一步所需的强酸性条件仅能分离出脱水查坦辛30。
