Pd-catalyzed synthesis of multi-aryl
7-azaindoles using sequential
arylation of 5-bromo-6-chloro-3-iodo-1-methyl-1H-pyrrolo[2,3-b] pyridine is established. Four diverse aryl groups are
installed in a chemo-selective fashion providing a general method
to synthesize sterically encumbered compounds and extended 7-azaindoles
in 48–95% yields. Three-selective sequential arylations at
C-3, C-5, and C-6 via Suzuki–Miyaura cross-coupling followed
by direct C-2 arylation using a Pd catalyst and AgOTf as an additive
are highlights of the present work. Interestingly, the tetra-aryl
7-azaindoles showed aggregate-induced emission (AIE) making it potentially
useful as fluorophores in OLEDs, sensors, and bio-imaging tools.
The Schiff base 4-hydroxy-benzoic acid (4-diethylamino-2-hydroxy-benzylidene) hydrazide (SL) was synthesized and characterized. Its antioxidant activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging action. Being a potent antioxidant its binding ability to the transport protein bovine serum albumin (BSA) was studied using fluorescence quenching and circular dichroism (CD) studies. The binding distance has been calculated by fluorescence resonance energy transfer (FRET) to be 1.85 Å and the Stern-Volmer quenching constant has been calculated to be (3.23 ± 0.45) × 10(5) M(-1). Quantum chemical analysis was carried out for the Schiff base using DFT with B3LYP and 6-311G** and related to the experimentally obtained results. For a deeper understanding of the mechanism of the interaction, the experimental data were complemented by protein-Schiff base docking calculations using Argus Lab.
Synthesis of new efficient compounds is becoming urgent due to the resistance of organisms to drugs. Salen derivatives have interesting therapeutic and industrial applications. A coumarin based derivative of salen, 7-hydroxy-8-((E)-((2-((E)-((7-hydroxy-5-methyl-2-oxo-3,8a-dihydro-2
Sequence-specific C-arylation strategies have
important applications in medicinal and material research. These strategies
allow C–C bond formations in a regioselective manner to synthesize
large molecular libraries for studying structure–activity profiles.
The past decade has seen the development of single C–C bond
forming reactions using various transition-metal catalysts, cryogenic
metalation strategies, and metal-free methods. Sequential arylations
of heterocycles allow for the formation of multiaryl derivatives and
are a preferred choice over de novo synthetic routes. This perspective
sheds light on recent strategic advances to develop various sequential
synthetic routes for the multiarylation of heteroarenes. This perspective
addresses many challenges in optimizing sequential routes with respect
to catalysts, reaction parameters, and various strategies adopted
to obtain diversely arylated products.
There is a continuing demand of new inhibitors of HIV-1
Integrase
(HIV-1 IN) due to mutations of HIV-1. This study aims to develop the
synthesis of 3,6-diaryl 7-azaindoles and introspect the role of aryl
groups on the strand transfer (ST) inhibition of HIV-1 IN. An efficient
and chemo-selective one-pot method is established for the synthesis
of the unexplored diverse C3 → C6 diaryl 7-azaindoles starting
from 6-chloro-3-iodo-N-protected 7-azaindoles. Here
we report Pd2dba3/SPhos catalyzed synthesis
of eight selective C3 monoaryl 7-azaindoles (10a–h) and eight C3,C6-diaryl 7-azaindoles (11a–f, 12a,b) with yields in the ranges of 67–93%
and 43–88% respectively. The synthesized derivatives inhibit
the strand transfer (ST) activity of HIV-1 IN enzyme at 10 μM
dose with 11d and 11f exhibiting %ST inhibitions
of 72% and 71%, respectively. SAR studies indicate the para-substitution
on the C3 aryl ring and C6 aryl is essential for enhanced %ST inhibition. 11b,c, 11e–f, and 12b showed lower cytotoxicity (IC50 > 200 μM) against TZM-bl cells. Molecular docking of the
diaryl
7-azaindoles and Raltegravir (RAL), to the PFV-integrase
revealed favorable binding interactions.
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