Methodological Development and Applications of Tryptamine-Ynamide Cyclizations in Synthesizing Core Skeletons of Indole Alkaloids

Abstract

Over the past two decades, synthetic strategies for synthesizing the skeletons of various indole alkaloids based on tryptamine-ynamide have been continuously developed and applied to the total syntheses or formal total syntheses of related molecules. In this synopsis, we summarized the cyclization pathways of tryptamine-ynamide under different catalytic conditions, emphasizing the reaction mechanism and applications in the syntheses of indole alkaloids.

One-Pot Reaction Sequence: N-Acylation/Pictet–Spengler Reaction/Intramolecular [4 + 2] Cycloaddition/Aromatization in the Synthesis of β-Carboline Alkaloid Analogues

“…Such pathways often involve Bischler–Napieralski or Pictet–Spengler reactions as the central step of the whole sequence. Recent syntheses, which include the aza-Friedel–Crafts reaction as the main step, should be mentioned here as well. , Usually, the first two reactions mentioned above, crucial in the formation of the β-carboline fragment, demand elevated temperatures, and various acidic or organometallic catalysts . These methods, though effective, may pose challenges such as the synthesis and application of complex or difficult to access reagents, , multistage protocols, diastereoselectivity issues, , and a complex apparatus design.…”

Investigation of UV Light-Promoted Synthesis of α-Sulfonyl Amides from N-Sulfonyl Ynamides

“…Due to the presence of a nitrogen atombearing an electron-withdrawing substituentdirectly linked to their carbon–carbon triple bond, ynamides behave as activated polarized alkynes that show unique reactivity and stability. These compounds are currently known as powerful synthetic intermediates for elegant construction of versatile N- containing molecules. , Regarding the direct synthesis of α-sulfonyl amides, only a few reports involve the use of ynamides as substrates (Scheme ). Wudl described in 2006 that ynamide A can undergo upon heating the N-to-C thermal migration of the tosyl group leading to a ketenimine intermediate that can be hydrated to give the α-tosylated amide A′ (Scheme a).…”