Short Total Synthesis of (+)-Colletotryptins B-D and Mucronatin B Derivative.

The short and first total synthesis of (+)-colletotryptins B-D, ent-colletotryptin A, and diastereomer of mucronatin B, which are a group of natural 3-(indol-2-yl)-3-(indol-3-yl)-1,2-propanediol (IIPDO) analogues containing two stereogenic centers at the C8' and C9' positions, isolated from endophytic fungus Colletotrichum sp. SC1355 and Tetrapterys mucronata, respectively, has been successfully accomplished in two and three steps with overall yields ranging from 28 to 54%. Key features of this synthesis include an innovative Bi(OTf)3-catalyzed stereoselective transindolylation of (S)-3,3'-di(1H-indol-3-yl)propane-1,2-diol. The operational simplicity, environmentally friendly catalyst, and broad functional group tolerance of this modular strategy render it suitable for adoption in both academic and industrial settings.

FeCl3·6H2O as a Mild Catalyst for Nucleophilic Substitution of Symmetrical Bis(indoyl)methanes.

In this paper, unsymmetrical bis(indolyl)methane (BIM) and 3-alkylindole derivatives are smoothly synthesized from symmetrical BIMs with a variety of nucleophiles including heteroaromatic/aromatic compounds, allylsilane and alkynylsilane. FeCl3·6H2O is found to be a mild and highly effective catalyst for this nucleophilic substitution reaction in which N-methyl-2-phenylindole behaves as a good leaving group in the Csp3-Csp2 bond cleavage reaction. The operational ease, nonexpensive and environmentally friendly catalyst, mild reaction conditions, broad functional group tolerance, and scalability of this reaction strategy are advantages of the present procedure.

Short Total Synthesis of (±)-Gelliusine E and 2,3'-Bis(indolyl)ethylamines via PTSA-Catalyzed Transindolylation.

A first and short total synthesis of the marine sponge 2,3'-bis(indolyl)ethylamine (2,3'-BIEA) alkaloid (±)-gelliusine E was performed in both a three-step divergent approach and a one-pot three-component approach with an overall yield of up to 58%. A key feature of the novel strategy is PTSA-catalyzed transindolylation of the readily synthesized 3,3'-BIEAs with tryptamine derivatives. The structure of the isolated natural product is revised as protonated (±)-gelliusine E (4'). By design, this modular route allows the rapid synthesis of other members of the 2,3'-BIEA family, for example, (±)-6,6'-bis-(debromo)-gelliusine F and analogues with step economy, operational simplicity, and reduced waste. Furthermore, their cytotoxicity in breast cancer cells was investigated.

Bi(OTf)3-Catalyzed One-Step Catalytic Synthesis of N-Boc or N-Cbz Protected α-Branched Amines.

In this paper, N-Boc and N-Cbz protected α-branched amines are synthesized directly from commercially available aromatic/heteroaromatic compounds, aldehydes, and tert-butyl or benzyl carbamate bearing a variety of substituents. Bismuth(III) triflate is found to be a highly effective catalyst for this one-pot, three-component coupling reaction. In addition, the use of mild reaction conditions, low catalytic loading, easy removal of the N-protective group, and one-step synthesis under "open-flask" are advantages of the present procedure.

Metal- and solvent-free synthesis of aniline- and phenol-based triarylmethanes via Brönsted acidic ionic liquid catalyzed Friedel-Crafts reaction.

A beneficial, scalable and efficient methodology for the synthesis of aniline-based triarylmethanes has been established through the double Friedel-Crafts reaction of commercial aldehydes and primary, secondary or tertiary anilines using Brönsted acidic ionic liquid as a powerful catalyst, namely [bsmim][NTf2]. This protocol was successfully performed under metal- and solvent-free conditions with a broad range of substrates, giving the corresponding aniline-based triarylmethane products in good to excellent yields (up to 99%). In addition, alternative aromatic nucleophiles such as phenols and electron-rich arenes were also studied using this useful approach to achieve a diversity of triarylmethane derivatives in high to excellent yields.

Involvement of p38 MAPK and ATF-2 signaling pathway in anti-inflammatory effect of a novel compound bis[(5-methyl)2-furyl](4-nitrophenyl)methane on lipopolysaccharide-stimulated macrophages.

Activated macrophages produce various pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) and cyclooxygenase (COX)-2-derived prostaglandin E2 (PGE2) during inflammatory response. However, overproduction of NO and PGE2 appears to be involved in pathogenesis of various inflammatory diseases. Therefore, inhibition of NO and PGE2 production might be useful for the treatment of inflammatory-related diseases. In this study, the bis[(5-methyl)2-furyl](4-nitrophenyl)methane or BFNM was evaluated for the anti-inflammatory activity and mechanism of action in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage. BFNM inhibited NO and PGE2 production in a concentration-dependent manner and down-regulated the expression of iNOS and COX-2 at mRNA and protein levels. BFNM suppressed nuclear translocation of NF-κB p65 subunit only very slightly, and failed to decrease NF-κB DNA binding activity. In contrast, the compound significantly reduced phosphorylation of p38 MAPK and ATF-2, a component of AP-1 known to be involved in the transcriptional regulation of iNOS and COX-2, in a dose-dependent manner in LPS-induced cells. Collectively, these results suggest that BFNM has an anti-inflammatory effect in RAW 264.7 macrophages, at least in part, by suppression of NO and PGE2 production. The inhibitory effect of BFNM is mediated mainly via the p38 MAPK/ATF-2 signaling pathway. Thus, BFNM would be a lead compound for the development of novel anti-inflammatory agents.

Green synthesis and anti-inflammatory studies of a series of 1,1-bis(heteroaryl)alkane derivatives.

Molecular iodine has been used as an efficient catalyst for a double Friedel-Crafts reaction of various heteroarenes, i.e. 2-methylfuran, 2-ethylfuran, 2-methylthiophene, pyrrole, N-methylpyrrole and indole, using aldehydes as alkylating agents under "open-flask" conditions with toluene or water as the reaction media. In the presence of 10 mol% iodine in toluene at room temperature, both aliphatic and aromatic aldehydes reacted smoothly to give the corresponding bis(heteroaryl)alkanes in good to excellent yields. Interestingly, with water as the solvent, the bis(heteroaryl)alkane adducts were obtained in moderate to good yields. The use of mild reaction conditions, low catalyst loadings, and eco-friendly reagents in a single step synthesis are the advantages of the present procedure. In an effort to discover novel non-steroidal anti-inflammatory agents, the synthesized bis(heteroaryl)alkanes were evaluated for the anti-inflammatory activity in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage model. These compounds (50 µM) significantly inhibited NO production and did not exhibit significant cytotoxic effects on macrophage cells. Among them, bis[(5-methyl)2-furyl](4-nitrophenyl) methane exhibited the most potent inhibition of NO with IC50 value of 42.4 ± 1.9, which is similar to that of the positive control, aminoguanidine (43.3 ± 2.5 µM). Thus, the bis[(5-methyl)2-furyl](4-nitrophenyl) methane could be considered a lead compound for the development of novel anti-inflammatory agents.

A direct catalytic asymmetric Mannich-type reaction via a dinuclear zinc catalyst: synthesis of either anti- or syn-alpha-hydroxy-beta-amino ketones.

The use of imines bearing a hydrolyzable nitrogen substituent in direct asymmetric Mannich reactions with alpha-hydroxyketones is developed. Previous work focused on the use of N-arylimines or nonenolizable imines, and the latter with only methoxy-substituted alpha-hydroxyacetophenones. Using a dinuclear catalyst devised from 2,6-di-(S)-2'-diphenylhydroxymethylpyrrolidino-N-methyl)-4-methylphenol and diethylzinc, a broad array of hydroxyacetylated aromatics, including phenyl, 2-furyl, 1-naphthyl, and 2-naphthyl, react well. In addition, the reactions focused on the use of enolizable imines. With the N-diphenylphosphinoyl, the reactions are anti selective with enantiomeric excesses ranging from 83 to 99%, except for the reaction of the 2-methoxy-2'-hydroxyacetylbenzene. With the N-Boc-imines, the reactions were syn selective with enantiomeric excesses from 90 to 94%. The dependence of the diastereoselectivity on the nature of the N-substituent presumably arises from the steric demands of the diphenylphosphinoyl group.