Solid-phase synthesis and spectral properties of 2-alkylthio-6H-pyrano[2,3-f]benzimidazole-6-ones: a combinatorial approach for 2-alkylthioimidazocoumarins.
The solid-phase synthesis of 2-alkylthio-6H-pyrano[2,3-f]benzimidazole-6-ones (2-alkylthioimidazocoumarins) is described. 7-Fluoro-4-methyl-6-nitro-2-oxo-2H-1-benzopyran-3-carboxylic acid was coupled to Rink amide resin via its carboxyl group. The resin-bound scaffold then underwent aromatic nucleophilic substitution with primary amines, followed by reduction of the nitro group with tin (II) chloride. Subsequent cyclization of the o-dianilino intermediates with thiocarbonyldiimidazole (TCD) afforded resin-bound 1,3-dihydro-2-thioxo-6H-pyrano[2,3-f]benzimidazole-6-ones, which were then S-alkylated with alkyl halides in the presence of N,N-diisopropylethylamine (DIEA). The desired products were obtained in good yield with high purity after trifluoroacetic acid cleavage. The unique spectral properties of 2-alkylthioimidazocoumarins indicate that they may be useful in photodynamic therapy.
Song
Aimin
A
Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis Cancer Center, 4501 X Street, Sacramento, California 95817, USA.
Zhang
Jinhua
J
Lebrilla
Carlito B
CB
Lam
Kit S
KS
D000478:Alkylation; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D013057:Spectrum Analysis; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D001562:Benzimidazoles; D003374:Coumarins; D013438:Sulfhydryl Compounds; C030123:coumarin; C031000:benzimidazole