Organic Chemistry Portal
Organic Chemistry Highlights

Monday, May 8, 2017
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: (-)-Tashiromine (Jacobsen), (+)-Neostenine (Sato/Chida), (-)-Sclerotiamide (Sun/Li), (+)-Minfiensine (Jiao), (+)-Conolidine (Fujii/Ohno), (+)-Peganumine A (Zhu)

Indolizidines, as exemplified by (-)-tashiromine (3), and quinolizidines are found in many natural products. Eric N. Jacobsen of Harvard University developed (J. Am. Chem. Soc. 2016, 138, 14848. DOI: 10.1021/jacs.6b09736) a general enantioselective route to these ring systems, illustrated by the organocatalyzed Sakurai cyclization of 1 to 2.

(+)-Neostenine (6), isolated from Stemona tuberosa, shows significant antitussive activity. Takaaki Sato and Noritaka Chida of Keio University closed (Chem. Eur. J. 2016, 22, 3300. DOI: 10.1002/chem.201600058) the seven-membered ring of 6 by iodide exchange of 4 followed by intramolecular alkylation.

(-)-Sclerotiamide (9), isolated from Aspergillus sclerotiorum, is the first non peptide-based natural product activator of caseinolytic protease P. Deqian Sun and Chaozhong Li of the Shanghai Institute of Organic Chemistry assembled (Angew. Chem. Int. Ed. 2016, 55, 10435. DOI: 10.1002/anie.201604754) 9 via the oxidative cyclization of 7 to 8.

The compact pentacyclic alklaloid (+)-minfiensine (12), isolated from the Nigerian tree Strychnos minfiensis, showed significant anticancer activity. En route to 12, Lei Jiao of Tsinghua University effected (Angew. Chem. Int. Ed. 2016, 55, 8090. DOI: 10.1002/anie.201602771) the enantioselective dearomative cyclization of 10 to 11.

(+)-Conolidine (15) was isolated from the small flowering plant Tabernaemontana divaricata, cultivated in China for the treatment of eye diseases. Nobutaka Fujii and Hiroaki Ohno of Kyoto University established (J. Org. Chem. 2016, 81, 5690. DOI: 10.1021/acs.joc.6b00720) two of the four rings of 15 by the Au-catalyzed enantioselective cascade cyclization of 13 to 14.

(+)-Peganumine A (19), isolated from the Syrian rue Peganum harmala, shows selective cytotoxic activity. Jieping Zhu of the Ecole Polytechnique Fédérale de Lausanne prepared (J. Am. Chem. Soc. 2016, 138, 11148. DOI: 10.1021/jacs.6b07846) the prochiral ketone 17 by cyclizing the isonitrile 16 with hydroxylamine. Addition of the tryptamine 18 in the presence of an organocatalyst delivered (+)-peganumine A (19).

D. F. Taber, Org. Chem. Highlights 2017, May 8.