546-09-8

Reductive late-stage functionalization of gibberellic acid is reported using three fluoroarylborane Lewis acids; (B(C6F5)3, B(3,5-C6H3(CF3)2), and B(2,4,6-C6H2F3)3) in combination with a tertiary silane and a borane (HBCat) reductant. In each case, C–O bond activation occurs, and different products are obtained depending on the reductant and catalyst employed.

The invention provides a novel, general, and facile strategy for the creation of small molecules with high structural and stereochemical complexity. Aspects of the methods include ring system distortion reactions that are systematically applied to rapidly convert readily available natural products to structurally complex compounds with diverse molecular architectures. Through evaluation of chemical properties including fraction of sp3 carbons, ClogP, and the number of stereogenic centers, these compounds are shown to be significantly more complex and diverse than those in standard screening collections. This approach is demonstrated with natural products (gibberellic acid, adrenosterone, and quinine) from three different structural classes, and methods are described for the application of this strategy to any suitable natural product.

It has been shown by the methods of 1H NMR and high-performance liquid chromatography with recording of UV spectra that in aqueous solutions of gibberellin A3, via gibberellenic acid, an unstable conjugated triene having λmax 326 nm is formed which is readily converted into allogibberic acid and is isolated as a mixture (1:2) with this acid.In the 1H NMR spectrum of the triene, confirming its structure, spin-spin coupling both of the H-5 proton and of the protons of the methyl group with all the H-1, H-2, and the H-3 protons is observed.The precursor of allogibberic acid has been ascribed the structure of (-)-13-hydroxy-19,20-dinorgibberella-1,3,9,16-tetraen-7-oic acid with a conjugated 1,3,9-trienic system.