Organic Chemistry Portal
Organic Chemistry Highlights

Monday, May 11, 2015
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: Indolizidine 223AB (Cha), Lepadiformine (Kim), Kainic Acid (Fukuyama), Gephyrotoxin (Smith), Premarineosin A (Reynolds)

Jin Kun Cha of Wayne State University prepared (Org. Lett. 2014, 16, 6208. DOI: 10.1021/ol503136s) the allene 1 by SN2' coupling of a cyclopropanol with a propargylic tosylate. Silver-mediated cyclization converted 1 into 2, that was reduced with diimide to the Dendrobates alkaloid Indolizidine 223AB (3).

Sanghee Kim of Seoul National University observed (Chem. Eur. J. 2014, 20, 17433. DOI: 10.1002/chem.201404316) high diastereoselectivity in the Ireland-Claisen rearrangement of 4 to 5. The acid 5 was the key intermediate for the synthesis of the tunicate alkaloid Lepadiformine (6).

Tohru Fukuyama of Nagoya University also used (Eur. J. Org. Chem. 2014, 4823. DOI: 10.1002/ejoc.201402452) an ester enolate Claisen rearrangement to set the relative and absolute configuration of 7. Pd-catalyzed cyclization then led to 8, that was carried on to the excitatory amino acid-receptor agonist Kainic Acid (9).

Gephyrotoxin (12) was so named because it incorporates structural elements from two different classes of the Dendrobates alkaloids. Martin D. Smith of the University of Oxford envisioned (Angew. Chem. Int. Ed. 2014, 53, 13826. DOI: 10.1002/anie.201409038) the cascade cyclization of deprotected 10 to give, after reduction, the ketone 11.

Zhen Yang of the Peking University Shenzen Graduate School showed (Chem. Eur. J. 2014, 20, 12881. DOI: 10.1002/chem.201403756) that the Rh carbene derived from 13 readily cyclized to an imine. The facial selectivity of the addition of the Grignard reagent 14 to that imine depended on the temperature of the reaction. At room temperature, 15 was formed. At low temperature, the other diastereomer predominated. Ring-closing metathesis was used for the elaboration of 15 to the Stemona alkaloid Tuberostemospiroline (16).

Kevin A. Reynolds of Portland State University prepared (J. Org. Chem. 2014, 79, 11674. DOI: 10.1021/jo5023553) 19 by condensation of the pyrrole 17 with the aldehyde 18. The biosynthetic enzyme, that they had overexpressed, oxidized 19 to the antimalarial alkaloid Permarineosin A (20).

D. F. Taber, Org. Chem. Highlights 2015, May 11.