Organic Chemistry Portal
Organic Chemistry Highlights

Monday, November 19, 2018
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: Lentiginosine (Orthaber/Samec), Sparteine (Breuning), Pancracine (Cossío), Akuammiline (Garg), Parvineostemonine (Gaich), Huperzine R (Yokoshima/Fukuyama)

Lentiginosine (3), isolated from the spotted locoweed Astragalus lentiginosus, has amyloglycosidase inhibitory activity. Andreas Orthaber of Uppsala University and Joseph S. M. Samec of Stockholm University showed that the free alcohol 1, prepared from D-galactose, could be cyclized directly to pyrrolidine 2, that was readily carried on to 3 (Chem. Eur. J. 2018, 24, 3488. DOI: 10.1002/chem.201705164).

(-)-Sparteine (6) is a particularly effective mediator of enantioselective metalation. Matthias Breuning of the University of Bayreuth developed an inside-out approach to 6 and related alkaloids, based on the diastereoselective reduction of 4 to 5 (Angew. Chem. Int. Ed. 2018, 57, 2432. DOI: 10.1002/anie.201712852). Peter O'Brien of the University of York described a complementary route to 6 (Angew. Chem. Int. Ed. 2018, 57, 223. DOI: 10.1002/anie.201710261) (not illustrated).

Fernando P. Cossío of the University of the Basque Country devised the organocatalyzed assembly of 9 by the addition of 7 to 8. The lactam 9 could be carried on by reduction and cyclization to the Amaryllidaceae alkaloid pancracine (10) (Angew. Chem. Int. Ed. 2018, 57, 668. DOI: 10.1002/anie.201708952).

The indole alkalkoid akuammiline (13) was isolated almost 100 years ago from the dogbane Picralima klaineana Pierre. The cyclization of 11 to 12 was a key early step in the first total synthesis of 13, by Neil K. Garg of UCLA (J. Am. Chem. Soc. 2018, 140, 6483. DOI: 10.1021/jacs.8b03404).

Parvineostemonine (17) was isolated from the medicinal root of the vine Stemona parviflora. Tanja Gaich of the University of Konstanz established a practical route to 17, based on the assembly of 16 by the diastereoselective dearomatizing addition of enantiomerically pure 15 to 14 (Chem. Eur. J. 2018, 24, 3994. DOI: 10.1002/chem.201800365).

Huperzine R (20), isolated from the club moss Lycopodium serratum, contains two interconnected medium rings. Satoshi Yokoshima and Tohru Fukuyama of Nagoya University solved this problem by cyclizing 18 to 19, five- and six-membered ring formation, followed by cleavage of the central bond (Org. Lett. 2018, 20, 119. DOI: 10.1021/acs.orglett.7b03555).

D. F. Taber, Org. Chem. Highlights 2018, November 19.