Alkyne [2 + 2 + 2]-Cyclotrimerization Approach for Synthesis of 6,7-Cyclopropylallocolchicinoids

Abstract

Employing a cobalt-catalyzed [2 + 2 + 2] alkyne cyclotrimerization as the final step, the short and efficient synthesis of cyclopropylallocolchicinoid and its analogues having functional group variations at C9 and/or C10 and C11 of ring C has been accomplished.

Colchicine Alkaloids and Synthetic Analogues: Current Progress and Perspectives

“…Several strategies have also been developed for the total synthesis of allocolchicine ( 2 ), which represents another biologically important colchicinoid (Scheme ). As key steps, the Diels–Alder reaction, , ene-yne metathesis, as well as transition-metal-catalyzed arylation and cycloaddition , reactions were exploited.…”

Total Synthesis of (±)-Allocolchicine and Its Analogues Using Co-Catalyzed Alkyne [2 + 2 + 2]-Cyclotrimerization

“…This led us to opt for an alternative route for the preparation of 3 , where we intended to employ Sonogashira cross-coupling at an elevated temperature to introduce the alkyne unit opted for previous synthesis. 14…”

“…13 We have recently documented the synthesis of a library focused on the cyclopropyl allocolchicinoids that have shown equipotent tubulin-binding ability when compared to the natural allocolchicine ( 1 ). 14 A large number of C ring-modified analogues of this cyclopropyl allocolchicinoids could be realized by virtue of using the alkyne [2 + 2 + 2]-cyclotrimerization 15,16 as the key reaction and importantly as the final event in our adopted approach. Given its simplicity and realization of a large number of analogues, especially with substituent alteration on ring C, we realized that adopting a similar cyclotrimerization approach will address the total synthesis of allocolchicine as well as the synthesis of ring C-modified allocolchicinoids.…”

Air‐Stable CpCoI–Phosphite–Fumarate Precatalyst in Cyclization Reactions: Comparing Different Methods of Energy Supply

“…Even today, this commercially available complex remains the catalyst of choice for many cobalt‐catalyzed cyclotrimerizations, although it usually requires significant amounts of energy for activation. Applications include the synthesis of natural products, especially those containing heterocyclic cores; examples for both include angucyclinones, (dehydro)tylophorine, (+)‐complanadine A, xylarinol A, and, recently, cyclopropylallocolchicinoid and (±)‐allocolchicine . Earlier reports on the photochemistry of CpCo(CO) 2 ( 1 ) discussing the possibility of the formation of clusters being regularly responsible for catalyzing the cyclotrimerizations have not been corroborated yet .…”