Tetramic acids and indole derivatives from amino acid β-keto esters

We report the activity of a synthetic arylomycin derivative against clinical isolates of coagulase-negative staphylococci (CoNS). Against many important CoNS, e.g. S. epidermidis, S. haemolyticus, S. lugdunensis, and S. hominis, we find that the arylomycin has activity equal to or greater than that of vancomycin, the antibiotic most commonly used to treat CoNS infections.

other polycyclic indole derivatives

None of the foregoing patents describes the indole derivatives ..
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Practical Methodologies for the Synthesis of Indoles ..

We report the first examples of a “BN-fused” indole, and we demonstrate that this new family of unnatural indole derivatives undergoes electrophilic aromatic substitution (EAS) reactions with the same regioselectivity as its organic analogue. Competition experiments reveal that N-t-Bu-BN-indole is more nucleophilic in EAS reactions than its carbonaceous counterpart. X-Ray structural analysis between BN indole and classic indole highlights significant differences in bond distances, in particular for bonds associated with the boron atom.

preparation of indole derivatives is a ..

Indole is one of the most ubiquitous heterocyclic motifs in nature. Due to the abundance of biologically active indole derivatives, the indole ring system has become an important structural component in drug discovery efforts. Consequently, the synthesis and functionalization of indoles has been a major focus in research, the expansion of the chemical space of accessible indole structures being one of the goals. An alternative approach to expand structural diversity is “elemental isosterism”. To this end, the BN/CC isosterism has recently emerged as a viable strategy to create biomimetic analogues of common structural units in organic molecules (e.g., olefin, benzene, and indene). Despite the recent advances in this area, the elemental isosterism of the biologically important indole has remained virtually unexplored. To date, the only BN-substituted indoles are phenylenediamine-type heterocycles containing an external BN unit as illustrated in 1 ()., To the best of our knowledge, electrophilic aromatic substitution (EAS), a crucial reaction of the biochemistry of indoles has not been demonstrated with these phenylenediamine-type BN indoles. Herein we report the first example of a “BN-fused” indole (e.g., heterocycle 2 in ), and we demonstrate that this new BN indole undergoes EAS reactions with the same regioselectivity as its organic analogue, N-t-Bu-indole 3.

chemical and pharmacological activity of important indole derivatives in ..
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or indole, in particular derivatives that ..

Herein, we would like to report a novel, straightforward, and one-pot synthesis of highly substituted 2-amino (hetero)-indole-3-carboxamides. 2-Amino-indole-3-carboxamides in the past have been synthesized by several step processes, for example, by [3,3]-sigmatropic rearrangement and intramololecular cyclization from N-arylhydroxamic acids and malononitrile, by nucleophilic aromatic substitution reaction with malondinitrile or cyanoaceticacid esters, followed by reduction (eq 1, ), or by a four-component reaction of pyridine or 3-picoline, chloroacetonitrile, malononitrile, and aromatic aldehydes, by the Nenitzescu reaction of primary ketene aminals and 1,4-benzo-quinones, by the reaction of 2-haloanilines and substituted acetonitriles, and other methods. Our synthetic approach involves a nucleophilic aromatic substitution reaction of a suitable o-halo-nitro-(hetero)aromate with a cyanoacetamide and a subsequent reductive cyclization. To the best of our knowledge, no such transformation has been described in a one-pot manner. Together with our recently described experimentally very simple one-pot access to hundreds of cyanoacetamides, we believe this is a valuable procedure of general interest to medicinal and organic chemists.

NMR Chemical Shifts of Common Laboratory Solvents …

We report the synthesis, stability and polymerase recognition of nucleoside analogs bearing single bromo- or cyano-derivatized phenyl rings and find that both modifications generally stabilize base pair formation to a greater extent than methyl or fluoro substitution.

Chapter 33 - Toxicology INTRODUCTION

The short reaction times suggest the initial formation of monoallylated products followed by a second N-allylation in most cases and cyclisation, although the exact order of these two steps is not apparent. Evidence for the formation of the N,N'-diallylated products was observed, e.g., by mass spectral analysis of reaction mixtures, but such products were never isolated. After 5 s reaction time, the red diindolone heterocycles 710 were already produced, an indication of the ease of the cascade processes. After 1 h reaction time, there was no evidence for the presence of the monoallylindigo products, and the spiro compounds were present in minor quantities. Instead, a greater proportion of the red diindolones was produced. After 3 h reaction time the spiro compounds 12–16 and azepinodiindolones 1718 predominate with a corresponding loss of the monoallylindigos and diindolones. This includes the more sterically demanding cinnamyl bromide and 1-bromo-2-butene which also gave rise to spiro heterocycles (16 and 15 respectively), the latter reported here for the first time. The products arising from oxidative cleavage, the N-allylisatins, are diminished under these optimised conditions, and appear to arise only after longer reaction times. The proposed mechanism for the formation of spiro derivatives 1216 was previously reported [].