Pictet-Spengler Cyclizationvs. Aminal Formation: Competing Reaction Pathways of Benzo[b][1,7]naphthyridines Controlled by the Configuration

Abstract

Diastereoisomeric benzo [b][1,7]naphthyridines 13a,b were synthesized in nine steps from l-DOPA employing a Lewis acid-catalyzed cyclization of N-(4-methylpent-3-enyl)-a-amino aldehydes as the key step. Under aprotic Pictet-Spengler conditions, compounds 13a,b undergo different reaction pathways depending on the relative configuration. Whereas trans,cis-diastereoisomer 13a yielded the desired Pictet-Spengler cyclization product albeit in very low yield, the corresponding concave-shaped all-cis-diastereoisomer 13b undergoes intramolecular aminal formation.

A novel isoquinoline alkaloid, DD-carboxypeptidase inhibitor, with antibacterial activity isolated from Streptomyces sp. 8812. Part II: Physicochemical properties and structure elucidation

“…To address in more depth the position of tautomeric equilibrium, we have performed the theoretical calculations of the 1 H, 13 C chemical shift and the geometry of all possible tautomers (see Supplementary Figure 2S) using the PCM protocol in the H 2 O box at the B3LYP/6-31/ +6(2d 18 ) basis set level. The chemical shift data are compiled in Supplementary Tables 1S-3S in the Supplementary materials along with the structures.…”