Synthesis (Stuttg). 2026 May;58(9):966-983. doi: 10.1055/a-2779-3222. Epub 2026 Jan 23.

ABSTRACT

1,1-disubstituted tetrahydroisoquinolines (THIQs) and tetrahydro-β-carbolines (THBCs) are key intermediates in the synthesis of various alkaloid natural products. These 1,1-disubstituted scaffolds are typically constructed via the Pictet-Spengler reaction. The asymmetric catalytic variant of this reaction enables access to stereochemically pure compounds with significant biological properties. This review focuses on recent progress in organocatalyzed and enzyme-catalyzed asymmetric Pictet-Spengler reactions to generate these 1,1-disubstituted motifs.

PMID:42807731 | PMC:PMC13618986 | DOI:10.1055/a-2779-3222