Organic Chemistry Portal
Organic Chemistry Highlights

Monday, April 19, 2021
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: Myrifabral B (Stoltz), Chilocorine C (Snyder), Stemofoline (Huang), Haliclonin A (Ishihara), Daphnezomine B (Li), Haouamine A (Chen)

Myrifabal B (3), isolated from the Chinese seaweed Myrioneuron faberi, showed anti-hepatitis C activity. Brian M. Stoltz of Caltech set the tricyclic core of 3 by the intramolecular Mannich cyclization of 1 to 2 (Chem. Sci. 2020, 11, 10802. DOI: 10.1039/D0SC01141J).

Chilocorine C (7) is one of an extensive family of ladybug alkaloids. Scott A. Snyder of the University of Chicago assembled the piperidine core 6 of 7 by the oxidative coupling of the amino acid 4 with the ketene silyl acetal 5, followed by reduction (J. Am. Chem. Soc. 2020, 142, 12027. DOI: 10.1021/jacs.0c04914).

Stemofoline (10), from Stemona japonica of Southeast Asia, reversed the multidrug resistance of certain types of cancer. En route to 10, Pei-Qiang Huang of Xiamen University cyclized the lactam 8 to the bridgehead bromide 9 (Nature Commun. 2020, 11, 5314. DOI: 10.1038/s41467-020-19163-4).

Haliclonin A (14), isolated from the marine sponge Haliclona sp. collected in Korean waters, displayed antimicrobial and anticancer activity. In the course of a synthesis of 14, Jun Ishihara of Nagasaki University devised the radical intramolecular cyclization of the selenocarbamate 11, with tandem alkylation by the allyl stannane 12, leading to the lactam 13 (Org. Lett. 2020, 22, 5046. DOI: 10.1021/acs.orglett.0c01627).

Daphnezomine B (17), from the Japanese shrub Daphniphyllum humile, showed significant activity against murine lymphoma L1210 cells. A key step in the synthesis of 17 reported by Chao Li of the National Institute of Biological Sciences, Beijing was the reductive cyclization of the diene 15 to the tetracyclic ketone 16 (J. Am. Chem. Soc. 2020, 142, 15240. DOI: 10.1021/jacs.0c06717).

Haouamine A (20), isolated from the Mediterranean tunicate Aplidium haouarianum, had remarkable activity against human colon carcinoma cells. David Y.-K. Chen of Seoul National University prepared the 11-membered ring of 20 by the iodide-mediated cyclization of 18 to 19 (Chem. Sci. 2020, 11, 8132. DOI: 10.1039/D0SC02299C). Hirokazu Tsukamoto of the Yokohama University of Pharmacy reported an alternative approach to 20 (Chem. Eur. J. 2020, 26, 12528. DOI: 10.1002/chem.202001756).

D. F. Taber, Org. Chem. Highlights 2021, April 19.