Microbial reduction of coumarin, psoralen, and xanthyletin by Glomerella cingulata

Microbial transformation of coumarin, psoralen, and xanthyletin was performed with the fungus Glomerella cingulata. The main reaction pathways involved reduction at α,β-unsaturated δ-lactone ring on coumarin analogue. Coumarin was metabolized by G. cingulata to give the corresponding reduced acid, hydrocoumaric acid. In the biotransformation of psoralen, two reduced metabolites, 6,7-furano-hydrocoumaric acid, and 6,7-furano-o-hydrocoumaryl alcohol were isolated from the incubation of psoralen. Xanthyletin was converted to reduced products 9,9-dimethyl-6,7-pyrano-hydrocoumaric acid and 9,9-dimethyl-6,7-pyrano-o-hydrocoumaryl alcohol by G. cingulata. The structures of the new compounds were characterized using spectroscopic techniques. In addition, all of compounds including methyl ester derivatives of the metabolites were tested for the β-secretase (BACE1) inhibitory activity in vitro. 6,7-Furano-hydrocoumaric acid methyl ester was shown to possess BACE1 inhibitory activity, and an IC₅₀ value was 0.84 ± 0.06 mM.     

Gold(I)-Catalyzed Benzylic C(sp3)−H Functionalizations: Divergent Synthesis of Indole[a]- and [b]-Fused Polycycles**

Phenyl azides substituted by an (alkylphenyl)ethynyl group facilitate benzylic sp³(C−H) functionalization in the presence of a JohnPhosAu catalyst, resulting in indole-fused tetra- and pentacycles via divergent N- or C-cyclization. The chemoselectivity is influenced depending on the counter-anion, the electron density of the α-imino gold(I) carbene, and the alkyl groups stabilizing the benzylic carbocation originating from a 1,5-hydride shift. An isotopic labeling experiment demonstrates the involvement of an indolylgold(I) species resulting from a tautomerization that is much faster than the deauration. The formation of a benzylic sp³(C−H) functionalization leading to an indole-fused seven-membered ring is also demonstrated.