Organic Chemistry Portal
Organic Chemistry Highlights

Monday, April 30, 2018
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: Crinine (Tang), Codonopsinine (Jung), Gephyrotoxin 287C (Amat), Kopsone (Huang/Yu/Hong), Dendrobine (Chen), Actinophyllic Acid (Chen)

In an elegant illustration of enantioselective desymmetrization, Wenjung Tang of the Shanghai Institute of Organic Chemistry cyclized (Chem. Sci. 2017, 8, 6247. DOI: 10.1039/C7SC01859B) 1 to 2. The tricyclic phosphoramide 2 was readily carried on to the tetracyclic alkaloid crinine (3).

Young Hoon Jung of Sungkyunkwan University used (Tetrahedron 2017, 73, 4458. DOI: 10.1016/j.tet.2017.06.002) stoichiometric mercuric triflate to cyclize 4 to 5. The cyclization set the last stereogenic center of the alkaloid codonopsinine (6).

Gephyrotoxin 287C (10) is one of only two tricyclic alkaloids isolated the skin exudate of the Colombian poison dart frog Dendrobates histrionicus. En route to 10, Mercedes Amat of the University of Barcelona assembled (Org. Lett. 2017, 19, 6654. DOI: 10.1021/acs.orglett.7b03381) the central skeleton 9 by combining the enone 7 with the enantiomerically-pure amine 8.

Sha-Hua Huang of the Shanghai Institute of Technology, Zhi-Xiang Yu of Peking University and Ran Hong, also of the Shanghai Institute of Organic Chemistry, demonstrated (Angew. Chem. Int. Ed. 2017, 56, 11599. DOI: 10.1002/anie.201706018) the power of the intramolecular nitroso ene reaction by selectively oxidizing 11 to 12. The lactam 12 was readily carried on to the alkaloid kopsone (13).

David Y. K. Chen of Seoul National University found (Angew. Chem. Int. Ed. 2017, 56, 12250. DOI: 10.1002/anie.201705713) that the cascade cyclization of 14 to 15 could be carried out in a single pot, but that the catalysts had to be added sequentially. Further manipulation of 15 led to dendrobine 16.

Professor Chen also designed (Angew. Chem. Int. Ed. 2017, 56, 12277. DOI: 10.1002/anie.201706312) a total synthesis of actinophyllic acid (20). A key step was the Pd-catalyzed addition of 18 to 17 to give 19.

D. F. Taber, Org. Chem. Highlights 2018, April 30.