David StC. Black

Synthesis, Reactivity and Biological Activity of Benzimidazoles

Benzimidazole is a biologically important scaffold which displays important biological activities. Recent progress in the synthesis and bioactivity of benzimidazoles is reviewed. New synthetic procedures, including microwave-assisted synthesis, solid phase synthesis, natural product synthesis, and synthesis of bisbenzimidazoles are briefly described. Functionalization and cyclization reactions of benzimidazoles lead to a wide variety of novel benzimidazole structures. Selected bioactivity, such as anti-infective, anti-inflammatory, antitumor and receptor agonist/antagonist activities are presented.

Synthesis and metal complexes of symmetrically N-substituted bispidinones

Abstract The symmetrically substituted bispidinones (9–23) were prepared by the Mannich reaction. The bispidinone (28) can be used to generate the diaminoethyl derivative (25) and the diphenoxy ether (32). The crystal structure of the glycinic bispidinone (20) is reported. Metal complexes of bispidinones (4), (35–54) were prepared with copper, palladium and platinum.

Substitution, oxidation and addition reactions at C-7 of activated indoles

Abstract 4,6-Dimethoxy-2,3-diphenylindole (1) undergoes acylation, bromination, oxidative coupling and acid-catalysed addition to aldehydes at C-7 to produce a range of 7-substituted indoles (3–11), the indolo-isatin (6), the 7,7′-bi-indolyls (14), (16), (18), and the 7,7′-di-indolylmethanes (20–31). Addition to cyclopentanone gave compound (32), while Michael addition to α,β-unsaturated ketones gave compound (33) and the non-benzenoid double adduct (34). Related reactions led to the formation of the ring-fused indoles (39) and (41). Some reactions of the related indole diester (2) are also reported.

Design, synthesis, and evaluation of fimbrolide-nitric oxide donor hybrids as antimicrobial agents.

Fimbrolides from marine algae have shown promising activity against quorum sensing (QS), a chief regulatory and communication system in bacteria controlling biofilm formation and virulence factor. Nitric oxide (NO) at sublethal concentration has also been reported to induce dispersal of bacterial biofilms and increase their susceptibility toward standard biocides and antibiotics. Therefore, the combination of QS inhibitors and NO donors has the potential to control the development of biofilm and promote their dispersion via a nonbactericidal mechanism. Inspired by these ideas, novel fimbrolide-NO donor hybrid compounds were designed and synthesized. Fimbrolide-NO hybrids 6b, 6f, and 14a were found to be particularly effective as antimicrobials compared to the nonhybrid natural fimbrolides as revealed by bioluminescent P. aeruginosa QS reporter assays and biofilm inhibition assays. Significantly, these fimbrolide-NO hybrids represent the first dual-action antimicrobial agent based on the baterial QS inhibition and NO signaling.

A direct synthesis of pyrrolophenanthridone alkaloids

Abstract Pyrrolophenanthridone alkaloids were easily synthesized by palladium acetate catalyzed arylation of N-acylindolines (5a-c) followed by dehydrogenation.

Calix[4]indoles: New Macrocyclic Tetra(indolylmethylene) Compounds with 2,7-Linkages

Abstract Some 7-hydroxymethyl-3-aryl-4,6-dimethoxyindoles 1 undergo acid catalysed cyclotetramerisation in addition to cyclotrimerisation to give the calix[4]indoles 3 as well as the calix[3]indoles 2 : the tetramers 3, which display a 1,3-alternate cube-like structure, can also be obtained by the acid catalysed dimerisation of 7-hydroxymethyl-2,7′-diindolylmethanes 7.

Palladium-catalysed intramolecular cyclisation of 7-halo-N-allyl-indoles

Abstract The N-allyl substituted-7-bromo-indoles (4–9) and the N-propargyl-7-bromo-indole(10) were prepared from the 7-bromo-indole (3). Compounds (4) and (7) undergo palladium-catalysed cyclisation to the pyrroloquinolines (11) and (13). Similar reactions of compounds (5), (6), (8) and (10) led to unstable cyclisation products, whilst compound (9) did not react. An attempt to prepare the 7-iodo analog of compound (3) resulted in formation of the 7,7′-bi-indolyl (2).

Reactions of ninhydrin with activated anilines : formation of indole derivatives

Abstract In benzene, ninhydrin undergoes electrophilic substitution at C2 of 3,5-dimethoxyaniline, leading to the indeno[1,2-b]indole (7), which can in turn be transformed into the fused indole derivatives (9), (17) and (19), the indolenines (15) and (16), the indolone (18), and the dihydroindole (8). The corresponding reaction in water undergoes electrophilic substitution at C4 to give compound (11)

Acid-catalysed reaction of activated indoles with methyl ketones

Abstract 4,6-Dimethoxy-3-methylindole can be converted by treatment with acetone or acetophenones in methanolic hydrochloric acid into ring-fused indoles in good yields.

Postulated electrocyclic reactions leading to endiandric acid and related natural products

It is postulated that racemic endiandric acid is formed from a phenyl polyene acid (2; n= 0) in three successive electrocyclic reactions: this is supported by the additional isolation from E. introrsa of the related racemic acids (7; n= 1) and (8).