ABSTRACT
Described herein is the enantioselective syntheses of (+)- and (-)-rishirilideâ B from the corresponding optically active ß-substituted tetralones, which were obtained by oxidative kinetic resolution based on α-hydroxylation in the presence of a chiral guanidine-bisurea bifunctional organocatalyst. Benzylic oxidation of the tetralones at C1 followed by regioselective isomerization of the oxabenzonorbornadiene structure led to rishirilideâ B. Our findings lead to the revision of the previously proposed (2R,3R,4R) absolute configuration of (+)-rishirilideâ B to (2S,3S,4S).
Subject(s)
Anthracenes/chemical synthesis , Organic Chemicals/chemistry , Anthracenes/chemistry , Boron Compounds/chemistry , Carbon-13 Magnetic Resonance Spectroscopy , Catalysis , Chromatography, High Pressure Liquid , Crystallography, X-Ray , Hydroxylation , Kinetics , Molecular Structure , Oxidation-Reduction , Proton Magnetic Resonance Spectroscopy , Stereoisomerism , Tetralones/chemistryABSTRACT
Novel guanidine-bisurea bifunctional organocatalysts 5 bearing a chiral pyrrolidine moiety on guanidine were designed with the guidance of DFT calculations. The resulting organocatalysts 5 were examined for α-hydroxylation of tetralone-derived ß-keto esters, and good selectivity was obtained with 5j bearing a methoxymethyl ether-containing chiral pyrrolidine moiety.
Subject(s)
Guanidines/chemistry , Pyrrolidines/chemistry , Tetralones/chemistry , Urea/analogs & derivatives , Catalysis , Hydroxylation , Quantum Theory , StereoisomerismABSTRACT
Dehydroxymethylepoxyquinomycin (DHMEQ, 1) is well known to inhibit nuclear factor-kappa B (NF-κB), which is closely associated with immune, inflammatory, and apoptotic processes as an inducible transcription factor. The inhibitory effect seems to be the result of the ring opening of an epoxide of 1 with Cys(38) of p65. We have synthesized an analog 4 containing a cyclopropanated quinol skeleton and examined its ability to inhibit NF-κB. Surprisingly, 4 showed no remarkable NF-κB inhibitory activity as determined through expression of cyclooxygenase-2 (COX-2) in an RAW264.7 macrophage cell line.