Synthesis of C-N Natural Products: (-)-α-Kainic Acid (Helmchen), (+)-Tylophorine (Opatz), (-)-Lycoperine A (Rychnovsky), Fluvirucidine A₂ (Suh), Complanidine A (Sarpong)

Günter Helmchen of the Ruprecht-Karls-Universität Heidelberg set (Org. Lett. 2010, 12, 1108. DOI: 10.1021/ol1001076) the absolute configuration of 3 by Ir*-mediated coupling of 1 with 2. Diastereoselective Pauson-Khand cyclization then led to (-)-α-Kainic Acid (5).

Till Opatz, now at the Johannes Gutenberg-Universität Mainz, showed (Org. Lett. 2010, 12, 2140. DOI: 10.1021/ol100652b) that the product from the Dibal reduction of 6 could be condensed with the amine 7 without epimerization. Kim cyclization then directly delivered the pentacyclic alkaloid (+)-Tylophorine (9).

The interesting dimeric alkaloid Lycoperine A (13) was recently isolated from the Japanese club moss Lycopodium hamiltonii. Scott D. Rychnovsky of the University of California, Irvine prepared (Org. Lett. 2010, 12, 72. DOI: 10.1021/ol902389e) 12 by double alkylation of the bis-nitrile 11 with the enantiomerically-pure allylic bromide 10. While the projected reductive decyanation of 12 failed, hydrolysis followed by diastereoselective reductive amination successfully gave 13.

Retrosynthetic analysis of Fluvirucinine A₂ (16) could lead to an acyclic amino acid, that could be cyclized to the macrolactam. Young-Ger Suh of Seoul National University took (Org. Lett. 2010, 12, 2040. DOI: 10.1021/ol100521v) a different approach, building up the fourteen-membered ring system by two four-carbon ring expansions, beginning with an enantiomerically-pure piperidine precursor. The second of these enolate-based aza-Claisen ring expansions is illustrated in the conversion of 14 to 15.

Richmond Sarpong of the University of California, Berkeley faced (J. Am. Chem. Soc. 2010, 132, 5926. DOI: 10.1021/ja101893b) a different sort of challenge in the synthesis of the dimeric Lycopodium alkaloid Complanadine A (19). Even with established access to monomers such as 17 and its precursors, it was not clear how the 5-position of the pyridine ring could be selectively activated for bond formation. The solution to this dilemma was found in the work of Hartwig. Following that precedent, Ir-catalyzed activation of 17 converted it cleanly into the boronate 18, that could then be coupled with a pyridone triflate to complete the synthesis of 19.