6714-14-3Relevant academic research and scientific papers
Synthesis of Nonracemic Pyrrolo-allocolchicinoids Exhibiting Potent Cytotoxic Activity
Shchegravina, Ekaterina S.,Knyazev, Dmitry I.,Beletskaya, Irina P.,Svirshchevskaya, Elena V.,Schmalz, Hans-Günther,Fedorov, Alexey Yu.
, p. 5620 - 5623 (2016)
An efficient eight-step semisynthetic approach towards nonracemic pyrrolo-allocolchicinoids starting from natural colchicine was developed by exploiting Pd-catalyzed domino Sonogashira coupling/5-endo-dig cyclization of a 2-iodo-trifluoroacetanilide intermediate to build up the heterocyclic ring system. The N-Me substitution of the pyrrole ring enhanced the antitumor activity of the prepared molecules by 2–3 orders of magnitude. Among the active compounds, the N-methylated colchicinoid exhibited powerful cytotoxic and antiproliferative properties at concentrations 1 nm.
A Facile Synthetic Approach to Nonracemic Substituted Pyrrolo-allocolchicinoids Starting from Natural Colchicine
Shchegravina, Ekaterina S.,Svirshchevskaya, Elena V.,Schmalz, Hans-Günther,Fedorov, Alexey Yu
, p. 1612 - 1622 (2019/03/26)
A six-step semisynthetic approach towards chiral nonracemic pyrrolo-allocolchicinoids starting from naturally occurring colchicine was developed. The synthetic scheme includes an electrocyclic tropolone ring contraction to afford allocolchicinic acid followed by the Curtius reaction, giving the corresponding aniline. The Sandmeyer reaction and copper-mediated hydrazination gave hydrazine-substituted allocolchicine. This was introduced into the Fischer indole synthesis, affording libraries of regioisomeric indole-based allocolchicine congeners.
