40341-58-0

Upstream product

• 186581-53-3 diazomethane 
• 41744-26-7 eupomatenoid 6 
• 917-54-4 methyllithium 
• 104-92-7 1-bromo-4-methoxy-benzene 
• 1056899-49-0 5-chloro-2-(4-methoxyphenyl)-3-methylbenzofuran 
• 66680-84-0 tributyl(propenyl)tin 
• 568593-05-5 2,3,5-tribromo-2,3-dihydrobenzofuran 
• 64150-67-0 2,3,5-tribromobenzofuran 
• 99660-97-6 dibromo-3,5 benzofuranne 
• 365448-06-2 5-bromo-2-(4-methoxyphenyl)-3-methylbenzo[b]furan 
• 365448-05-1 3,5-dibromo-2-(4-methoxyphenyl)benzo[b]furan 
• 23145-07-5 5-bromobenzofuran 
• 489422-80-2 3-bromo-2-(4-methoxyphenyl)-5-(prop-1-enyl)benzo[b]furan 
• 568593-04-4 2-(4-Methoxy-phenyl)-3-methyl-5-((E)-propenyl)-benzofuran 

Relevant academic research and scientific papers

Activity of neolignans isolated from Piper regnellii (Miq.) C. DC. var. pallescens (C. DC.) Yunck against Trypanosoma cruzi

The in vitro antiproliferative effects of 4 neolignans purified from the ethyl-acetate extract from leaves of Piper regnellii (Miq.) C. DC. var. pallescens (C. DC.) Yunck against Trypanosoma cruzi were investigated. These isolated compounds were identified through spectral analyses of UV, EI-MS, 1H-, 13C-NMR, H-H COSY, gNOE, HETCOR, and HMBC. The compounds eupomatenoid-5, eupomatenoid-6, and conocarpan showed considerable activity against epimastigote forms of T. cruzi, with 50% inhibition concentrations (IC50) of 7.0, 7.5, and 8.0 μg/ml respectively. After methylation, these compounds showed a lessened inhibitory activity to the growth of the protozoan, suggesting that loss of the hydroxyl group from their molecules reduces the activity. The compound eupomatenoid-3 showed lower activity than the hexane fraction. Eupomatenoid-5 was significantly more active than benznidazole, the antiparasitic drug of choice for treatment of Chagas' disease. The crude extract, hexane fraction, and eupomatenoid-5 caused no lysis in sheep blood at concentrations which inhibit the growth of epimastigote forms. The compound eupomatenoid-5 showed low cytotoxic effects against Vero cells. These results provide new perspectives on the development of novel drugs obtained from natural products with trypanocidal activity. However, the extracts and active compound isolated from P. regnellii var. pallescens should be further studied in animal models for in vivo efficacy.

Synthesis of potential allosteric modulators of Hsp90 by chemical glycosylation of Eupomatenoid-6

Hsp90 (Heat shock protein-90) is a chaperone protein and an established anti-apoptotic target in cancer therapy. Most of the known small-molecule inhibitors that have shown potent antitumor activity target the Hsp90 N-terminal domain and directly inhibit its ATP-ase activity. Many of these molecules display important secondary effects. A different approach to Hsp90 inhibition consists of targeting the protein C-terminal domain (CTD) and modulating its chaperone activity through allosteric effects. Using an original computational approach, allosteric hot-spots in the CTD have been recently identified that control interdomain communication. A combination of virtual and experimental screening enabled identification of a rhamnosylated benzofuran (Eupomatenoid-2) as a lead for further development. In this paper we describe glycodiversification of Eupomatenoid-2 using chemical glycosylation of the 2-(4′-hydroxyphenyl)benzofuran aglycon (a.k.a. Eupomatenoid-6). Glycosylation of the phenol by glycosyl bromides under basic conditions afforded the desired products in the gluco-, galacto-, and fuco-series. This approach failed in the manno- and rhamno-series. However, mannosylation and rhamnosylation of Eupomatenoid-6 could be obtained under carefully controlled acidic conditions, using O-benzoxazolyl imidate (OBox) donors. The glycosides obtained are currently under investigation as modulators of Hsp90 chaperone activity.

One-pot synthesis of benzofurans via palladium-catalyzed enolate arylation with o-bromophenols

(Chemical Equation Presented) A one-pot synthesis of benzofurans which utilizes a palladium-catalyzed enolate arylation is described. The process demonstrates broad substrate scope and provides differentially substituted benzofurans in moderate to excelle

Regioselective C-C bond formation reactions on 2,3-dibromo- and 2,3,5-tribromobenzofuran as an access to multiply substituted benzofurans. Total syntheses of eupomatenoids 3, 4, 5, 6, and 15

Regioselective C-C-bond formation reactions at 2,3-dibromobenzofuran (1) and 2,3,5-tribromobenzofuran (6) were studied. Pd-catalyzed Sonogashira and Negishi cross-coupling occurred with perfect regioselectivity at carbon atom C-2 to provide 2-substituted 3-bromobenzofurans (12, 14) and 3,5-dibromobenzofurans (17, 18) in 50-91% yield. A regioselective displacement of the bromine substituents in 3,5-dibromobenzofurans 18 was achieved by a halogen-metal exchange reaction at carbon atom C-3 and by a Nicatalyzed Kumada cross-coupling at C-5. The methodology was applied to the synthesis of eupomatenoids 3, 4, 5, 6, and 15 (5). The synthesis of these compounds was achieved in overall yields of up to 60%.

Synthesis of eupomatenoids by three consecutive transition metal-catalyzed cross-coupling reactions

Six different eupomatenoids (1a-c, 1f-h) were prepared from 2,3,5-tribromobenzofuran (2) in a concise and high-yielding synthetic sequence. The overall yields vary between 29 and 60% over four to six steps. Key to the success of the syntheses is the high

2,3-Disubstituted 2,3,5-trisubstituted benzofurans by regioselective Pd-catalyzed cross-coupling reactions; a short synthesis of eupomatenoid-15

2,3-Dibromobenzofuran (1) 2,3,5-tribromobenzofuran (2) undergo regioselective Sonogashira- Negishi-type cross-coupling reactions at the 2-position. Subsequent substitution reactions at C-3 are possible for the cross-coupling products obtained from compoun

LIGNANS FROM KRAMERIA IXINA

From a methylene chloride extract of the roots of Krameria ixina nine new neolignans/nor-neolignans besides 24-methylenecycloartanol and eight further lignan-type compounds already known from other Krameriaceae were isolated. Key Word Index - Krameria ixi