20628-09-5Relevant articles and documents
Enantioselective synthesis of encecaline-derived potent antimalarial agents
Harel, Dipak,Schepmann, Dirk,Brun, Reto,Schmidt, Thomas J.,Wuensch, Bernhard
, p. 7342 - 7349 (2013)
The high antiplasmodial activity of racemic benzylamines rac-1 and rac-2 stimulated the synthesis of pure enantiomers. Ellman's chiral sulfinamides (S)-6 and (R)-6 were used as chiral auxiliaries. Condensation of prochiral ketone 5 with enantiomerically pure sulfinamides (S)-6 and (R)-6 and subsequent NaBH 4 reduction provided predominantly unlike configured diastereomers (S,R)-8 and (R,S)-8 (ratio unlike-8: like-8 = 90:10). The same transformation of phenol 4 led to the diastereomeric sulfinamides (S,R)-12 and (S,S)-12 in the ratio 60:40. Acid hydrolysis of the diastereomerically pure sulfinamides followed by monobenzylation yielded the enantiomerically pure benzylamines (R)-1, (S)-1, (R)-2 and (S)-2. The enantiomeric purity of the products was proven by chiral HPLC and the absolute configuration by CD-spectroscopy. Generally, benzylamines with (R)-configuration show higher antiplasmodial activity than their corresponding (S)-configured enantiomers. Phenol (R)-2 represents a very potent lead against P. falciparum, with an IC50 value of only 0.026 μM against the NF54 strain. The very high eudismic ratio of 34 indicates the enantioselective interaction of phenol (R)-2 with a particular target protein of P. falciparum.
The oligomerization and acylation of precocene I
Fraga, Braulio M.,Cabrera, Inmaculada
, p. 8078 - 8084 (2016)
The oligomerization of precocene I with Br?nsted and Lewis acids has been studied. In this way, the reaction of this chromene with HCl/MeOH gave two dimers, a trimer, a linear tetramer and a mixture of pentamers, whilst with FeCl3/HOAc a dimer and six cyclic tetramers were obtained. The cyclization of linear tetramers occurs between C-4? and C-6 or, in lower yield, between C-4? and C-8. In the formation of linear tetramers the C-8 functionalization was not detected, which could indicate that it occurs during the cyclization process. Moreover, oxidative one-electron coupling reactions were also observed in the treatment of precocene I with FeCl3/HOAc. On the other hand, the reaction of precocene I with FeCl3/Ac2O produced 6-acylation leading to the natural chromene encecalin.
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.
experimental part, 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.
Cyclization of o-(3-hydroxy-3-methylbutynyl)-phenols with boron tribromide to 4-bromo-2,2-dimethylchromenes and their electroreduction to 2,2-dimethylchromenes
Tsukayama, Masao
, p. 1131 - 1142 (2007/10/03)
Cyclization of o-(3-hydroxy-3-methylbutynyl)phenols (2) with boron tribromide gave easily 4-bromo-2,2-dimethylchromenes (3). Electrolytic reduction of 3 at a Hg-pool electrode afforded the corresponding 2,2-dimethylchromenes (6) in high yields.
Bentonitic Earth Catalyzed Rearrangement of Aryl 1,1-Dimethyl-propargyl Ethers. Synthesis of 2,2-Dimethyl-2H-1-benzopyrans
Cruz-Almanza, Raymundo,Perez-Flores, Francisco,Brena, Leonardo,Tapia, Eva,Ojeda, Reyna,Fuentes, Aidee
, p. 219 - 222 (2007/10/02)
Mexican Bentonitic earth (Tonsil) catalyzed the Claisen rearrangement of aryl 1,1-dimethylpropargyl ethers under mild conditions to provide 2,2-dimethyl-2H-1-benzopyrans.The synthesis of encecalin 2f and desmethoxyencecalin 2i, two biologically active products among other natural products (2b, 2e) was performed by this procedure.
A New Electrosynthesis of 2,2-Dimethylchromenes from 2-(1-Bromo-1-methylethyl)benzofurans
Tsukayama, Masao,Utsumi, Hideyuki,Kunugi, Akira
, p. 615 - 616 (2007/10/02)
Electrolytic reduction of 2-(1-bromo-1-methylethyl)benzofurans in acetonitrile affords the corresponding 2,2-dimethylchromenes in good yields even in the absence of a proton donor and comprises the cleavage of a carbon-bromine bond followed by ring expansion.
PHOTOCHEMISTRY OF 7-ACETOXYBENZOPYRAN DERIVATIVES. SYNTHESIS OF EUPATORIOCHROMENE AND ENCECALIN
Miranda, Miguel A.,Primo, Jaime,Tormos, Rosa
, p. 7593 - 7600 (2007/10/02)
The photolysis of the 7-acetoxybenzopyran derivatives 1a-5a has been carried out.Chromen 1a was found to undergo extensive photopolymerization.Chromanone 2a underwent a rather inefficient photo-Fries rearrangement to the 6- and 8- acetyl derivatives 2b and 2c.Diacetoxychromene 3a gave the unsaturated ketone 8 as the main product, besides its deacetylation analogue 9 and chromanone 11.Diacetoxychroman 4a afforded a mixture of four C-acetyl products: 1b, 1c, 2b and 2c, together with chromene 1a and chromanone 2a.Finally, irradiation of chroman 5a gave rise to a mixture of the two possible photo-Fries products 5b (43percent) and 5c (52percent).The mechanistic implications of the above results are discussed, with special emphasis on the photoreactivity of the phenyl ester as compared with that of the pyran ring, the enol ester and the benzyl ester moieties.The synthetic applications of these transformations are illustrated with the preparation of eupatoriochromene 1b and encecalin 1e.
HETEROCYCLES FROM DIACETYL PHENOLS: SYNTHESIS OF BENZODIPYRANS, ACETYLCHROMENES AND PYRANOBENZISOXAZOLES
Banerji, Asoke,Kalena, Govind P.
, p. 711 - 718 (2007/10/02)
Novel and facile syntheses of benzodipyrans, acetylchromenes and pyranolbenzisoxazoles from 2,4- and 4,6-diacetylresorcinols have been described.Regioselective condensations and reductions have been used as the key steps.
Acylation of 2,2-Dimathyl-2H-chromenes
Yamaguchi, Seiji,Yamamoto, Satoru,Abe, Shoichi,Kawase, Yoshiyuki
, p. 442 - 445 (2007/10/02)
Orientation in acylation reactions of 2,2-dimethyl-2H-chromenes was studied.Five acetylchromenes were obtained with two methods and six formylchromenes were obtained with a third method.Demethylation of four acyl-methoxy-substituted chromenes gave the corresponding acylchromenols. 2,2-Dimethyl-2H-chromene-6-carboxylic acid (anofinic acid) was also obtained by oxidation of 6-formylchromene.
