Synthesis of the C₁₈‐Norditerpenoid Alkaloid Neofinaconitine: A Lesson in Convergent Synthesis Planning

Abstract

Hexacyclic framework: The total synthesis of the complex C18 -norditerpenoid alkaloid neofinaconitine has been achieved by a convergent approach. This remarkable synthesis featured two Diels-Alder cycloadditions and subsequent Mannich-type N-acyliminium and radical cyclizations to establish the unique hexacyclic core structure of the target molecule.

The 1α-hydroxy-A-rings of norditerpenoid alkaloids are twisted-boat conformers

“…2) was used for designing synthetic approaches starting with analogues of C/D-rings. 48 Apart from the popular drawings A and B, an uncommon depiction C1 was also used, 49,50 in which the relationship between the A/E/Ftricycle and C/D-bicycle are distinctly expressed, and these two cycles are clearly linked by bond C7-C8 and bond C10-C11 perhaps motivating retrosynthetic analysis. As the D-ring adopts a mono-attened boat conformation with C14 at the ap, thus depiction C1 is slightly revised to C2.…”

Recent Advances in the Chemistry of Saturated Annulated Nitrogen-Containing Polycyclic Compounds

“…Most of C 19 -diterpene alkaloids belong to the aconitine and lycoctonine types. The main representatives of C 20 -diterpene alkaloids correspond to atisine and napelline types [ 58 , 59 , 60 , 61 , 62 , 63 ]. Diterpene alkaloids exhibited a pronounced cytotoxic effect against human tumor cells (A-549, DU-145, MDA-MB-231, MCF-7, HER2, and KB) [ 64 , 65 ].…”