Organic Chemistry Portal
Organic Chemistry Highlights

Monday, November 20, 2017
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: Strictamine (Gaich), Strictamine (Snyder), Corymine (Sun/Li), Lycodoline (Fan), Mitomycin K (Yang), Lasubine I (Takayama)

Tanja Gaich of the University of Konstanz showed (Chem. Eur. J. 2017, 23, 3938. DOI: 10.1002/chem.201605361) that alkylation of 1 with 2 followed by Stevens [2,3]-sigmatropic rearrangement delivered 3. The amine 3 could be carried on to strictamine (4).

Scott A. Snyder of the University of Chicago developed (Org. Lett. 2017, 19, 1004. DOI: 10.1021/acs.orglett.6b03839) a complementary route to strictamine (4). The indole 5, prepared by asymmetric propargylation, was cyclized to the amine 6.

Deqian Sun and Chaozhong Li of the Shanghai Institute of Organic Chemistry envisioned (Angew. Chem. Int. Ed. 2017, 56, 7484. DOI: 10.1002/anie.201704086) a route to corymine 9 via the allene 8. The eight-membered ring of 8 was prepared by contraction of the more readily prepared twelve-membered ring of 7.

Building on the work of Kraus, Chun-An Fan of Lanzhou University showed (J. Am. Chem. Soc. 2017, 139, 7095. DOI: 10.1021/jacs.7b03280) that the bridgehead enone from Pd oxidation of the silyl enol ether derived from 10 could be trapped by acetate. Reductive amination of that product with 11 led to 12, presumably via β-elimination of the acetate. The diol 12 was readily cyclized to lycodoline 13, that in turn was carried on to several other alkaloids.

Dan Yang of the University of Hong Kong devised (Angew. Chem. Int. Ed. 2017, 56, 5886. DOI: 10.1002/anie.201701895) the enantioselective cyclization of 14 to 15. The single stereogenic center of 15 was used to direct the several stereogenic centers of mitomycin K (16).

Hiromitsu Takayama of Chiba University found (Tetrahedron Lett. 2017, 58, 223. DOI: 10.1016/j.tetlet.2016.12.008) that the t-butyl sulfonyl protecting group of 17 was best for the organocatalyzed enantioselective cyclization to 18. Deprotection followed by further cyclization led to lasubine I (19).

D. F. Taber, Org. Chem. Highlights 2017, November 20.