69309-19-9Relevant academic research and scientific papers
Natural product derived antiprotozoal agents: Synthesis, biological evaluation, and structure-activity relationships of novel chromene and chromane derivatives
Harel, Dipak,Schepmann, Dirk,Prinz, Helge,Brun, Reto,Schmidt, Thomas J.,Wünsch, Bernhard
, p. 7442 - 7448 (2013/10/21)
Various natural products with the chromane and chromene scaffold exhibit high antiprotozoal activity. The natural product encecalin (7) served as key intermediate for the synthesis of different ethers 9, amides 11, and amines 12. The chromane analogues 14 and the phenols 15 were obtained by reductive amination of ketones 13 and 6, respectively. Angelate 3, ethers 9, and amides 11 did not show considerable antiprotozoal activity. However, the chromene and chromane derived amines 12, 14, and 15 revealed promising antiprotozoal activity and represent novel lead compounds. Whereas benzylamine 12a and α-methylbenzylamine 12g were active against P. falciparum with IC 50 values in the range of chloroquine, the analogous phenols 15a and 15b were unexpectedly 10- to 25-fold more potent than chloroquine with selectivity indexes of 6760 and 1818, respectively. The phenylbutylamine 14d based on the chromane scaffold has promising activity against T. brucei rhodesiense and L. donovani.
Encecalol angelate, an unstable chromene from Ageratum conyzoides L.: Total synthesis and investigation of its antiprotozoal activity
Harel, Dipak,Khalid, Sami A.,Kaiser, Marcel,Brun, Reto,Wuensch, Bernhard,Schmidt, Thomas J.
, p. 620 - 625 (2012/06/01)
Ethnopharmacological relevance: In agreement with ethnomedicinal reports, the dichloromethane extract of Ageratum conyzoides L. (Asteraceae) was recently shown to be of considerable activity against Trypanosoma brucei rhodesiense, the etiologic agent of East African Human Trypanosomiasis (East African Sleeping Sickness). Isolated compounds, namely, methoxylated flavonoids as well as the chromene derivative encecalol methyl ether, were less active than the crude extract. The activity of the extract was found to decrease considerably while stored in solution. An unstable compound was detected in the fresh extract by HPLC, which was converted rapidly into the encecalol methyl ether while stored in methanolic solution. This compound, deemed to represent a constituent with antitrypanosomal activity, could not be isolated from the extract in intact form. Aim of the study: To elucidate the structure of this unstable compound and to investigate its potential role in the antitrypanosomal activity of the total extract. Materials and Methods: UHPLC/ESI-qQTOF MSMS and NMR data of the degraded product indicated its chemical identity as encecalol angelate (1) which was therefore prepared by total synthesis via a linear six steps synthesis, starting from resorcinol and 2-methylbut-3-en-2-ol. Results: Total synthesis, in an overall yield of 15%, led to pure 1, which was chromatographically and spectroscopically identical with the natural product. The compound degraded in methanol with a half-life of approximately 6 h to yield encecalol methyl ether (2). The antiprotozoal activity of synthetic encecalol angelate against T. brucei rhodesiense as well as T. cruzi, Leishmania donovani and Plasmodium falciparum was investigated and found to be quite low. Conclusions: The synthetic approach applied here for the first time also provides access to the related bioactive chromenes encecalin (7) and encecalol (8) with improved yields compared with reported methods. Encecalol angelate, however, is most likely not responsible for the high antitrypanosomal activity of the freshly prepared dichloromethane extract of A. conyzoides.
Synthesis of Naturally Occurring p-Hydroxyacetophenone Derivatives, III
Bohlmann, Ferdinand,Stoehr, Frank-Michael
, p. 185 - 191 (2007/10/02)
Starting with different p-hydroxyacetophenone dervatives ten naturally occurring compounds have been synthesized.The synthesis of the vinyl chromene 18 gave unexpected difficulties as the dehydration of the corresponding alcohol was not successful.However
