Organic Chemistry Portal
Organic Chemistry Highlights

Monday, November 24, 2014
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: Penaresidin A (Subba Reddy), Allokainic Acid (Saicic), Sedacryptine (Rutjes), Lepistine (Yokoshima/Fukuyama), Septicine (Hanessian), Lyconadin C (Dai)

Penaresidin A (3), isolated from the Okinawan marine sponge Penares sp., is a potent activator of actomyosin ATPase. B.V. Subba Reddy of the Indian Institute of Chemical Technology prepared (Tetrahedron Lett. 2014, 55, 49. DOI: 10.1016/j.tetlet.2013.10.095) the azetidine ring of 3 by mesylation of the hydroxy sulfonamide 2 followed by cyclization.

Allokainic Acid (6) has become a useful tool for neurological studies. Radomir N. Saicic of the University of Belgrade found (Org. Lett. 2014, 16, 34. DOI: 10.1021/ol4028557) that the Tsuji-Trost cyclization of 4 to 5 proceeded with high diastereoselectivity, presumably by way of the enamine of the aldehyde.

Floris P. J. T. Rutjes of Radboud University Nijmegen prepared (Org. Lett. 2014, 16, 2038. DOI: 10.1021/ol500633u) the starting material 7 for (-)-Sedacryptine (9) via an enantioselective Mannich addition. The reagent of choice for the Aza-Achmatowicz rearrangement of 7 to 8 proved to be mCPBA.

The intriguing tricyclic alkaloid (-)-Lepistine (12) was isolated from the mushroom Clitocybe fasciculate. En route to the first-ever synthesis of 12, Satoshi Yokoshima and Tohru Fukuyama of Nagoya University cyclized (Org. Lett. 2014, 16, 2862. DOI: 10.1021/ol5010033) the glycidol-derived sulfonamide 10 to the azacycle 11.

(+)-Septicine (15) is the biogenetic precursor to the phenanthrene alkaloid (+)-Tylophorine. Stephen Hanessian of the Université de Montréal prepared (Org. Lett. 2014, 16, 232. DOI: 10.1021/ol403229q) 15 by condensing the proline-derived ketone 13 with the aldehyde 14.

Mingji Dai of Purdue University elaborated (Angew. Chem. Int. Ed. 2014, 53, 3922. DOI: 10.1002/anie.201400416) the amine 19 to the enone 20 by intramolecular Mannich alkylation followed by methylenation and allylic oxidation. Condensation with the sulfoxide 21 then delivered Lyconadin C (22).

D. F. Taber, Org. Chem. Highlights 2014, November 24.