477-27-0Relevant articles and documents
Synthesis and antiproliferative screening of novel analogs of regioselectively demethylated colchicine and thiocolchicine
Czerwonka, Dominika,Huczyński, Adam,Katrusiak, Andrzej,Maj, Ewa,Sobczak, Szymon,Wietrzyk, Joanna
supporting information, (2020/03/17)
Colchicine, a pseudoalkaloid isolated from Colchicum autumnale, has been identified as a potent anticancer agent because of its strong antimitotic activity. It was shown that colchicine modifications by regioselective demethylation affected its biological properties. For demethylated colchicine analogs, 10-demethylcolchicine (colchiceine, 1) and 1-demethylthiocolchicine (3), a series of 12 colchicine derivatives including 5 novel esters (2b-c and 4b-d) and 4 carbonates (2e-f and 4e- f) were synthesized. The antiproliferative activity assay, together with in silico evaluation of physicochemical properties, confirmed attractive biological profiles for all obtained compounds. The substitutions of H-donor and H-acceptor sites at C1 in thiocolchicine position provide an efficient control of the hydration affinity and solubility, as demonstrated for anhydrate 3, hemihydrate 4e and monohydrate 4a.
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.
Enantioselective total synthesis of (-)-colchicine, (+)-demecolcinone and metacolchicine: Determination of the absolute configurations of the latter two alkaloids
Chen, Bo,Liu, Xin,Hu, Ya-Jian,Zhang, Dong-Mei,Deng, Lijuan,Lu, Jieyu,Min, Long,Ye, Wen-Cai,Li, Chuang-Chuang
, p. 4961 - 4966 (2017/07/10)
Here, we describe a concise, enantioselective, and scalable synthesis of (-)-colchicine (9.2% overall yield, >99% ee). Moreover, we have also achieved the first syntheses of (+)-demecolcinone and metacolchicine, and determined their absolute configurations. The challenging tricyclic 6-7-7 core of colchicinoids was efficiently introduced using an intramolecular oxidopyrylium-mediated [5 + 2] cycloaddition reaction. Notably, the synthesized colchicinoid 23 exhibited potent inhibitory activity toward the cell growth of human cancer cell lines (IC50 = ～3.0 nM), and greater inhibitory activity towards microtubule assembly than colchicine, making it a promising lead in the search for novel anticancer agents.
