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Oxidative functionalization of a halimane diterpenoid achieved by fungal transformation

Authors:

Monteiro, Afif Felix 1, 2 ;  Righetto, Gabriela Marinho 3 ;  Simoes, Laura Vilar 2 ;  de Almeida, Larissa Costa 4 ;  Costa-Lotufo, Leticia Veras 4 ;  Baratella da Cunha Camargo, Ilana Lopes 3 ; Castro-Gamboa, Ian 2


Abstract:

Regio and stereoselective activation of sp3 CH bonds remain one of the major advantages of biocatalysis over traditional chemocatalytic methods. Herein, we describe the oxy-functionalization of halimane diterpenoid 1 by whole cells of three filamentous fungi, aiming to obtain derivatives with desirable biological properties. After incubating 1 with Fusarium oxysporum, Myrothecium verrucaria, and Rhinocladiella similis at different concentrations and incubation times, four known (3, 5, 6, and 7) and three new (2, 4, and 8) halimane derivatives were obtained and characterized. F. oxysporum catalyzed the hydroxylation of positions C-2 (2) and C-7 (4), while R. similis simultaneously mediated the 2-oxo-functionalization and the hydration of 13,14-(CC)double bond belonging to an α,β-unsaturated carbonyl system (8). Compounds 1–7 were non-cytotoxic against HCT-116 and MCF-7 cancer cell lines at tested concentrations. However, substrate 1 displayed moderate reduction ability against biofilm produced by Staphylococcus epidermidis ATCC35984 (84% at 1.6 mM), and this effect was retained to some extent by derivatives 4 and 7. These results emphasize the prominent potential of filamentous fungi associated with the microbiota of medicinal plants as versatile catalysts for singularly useful reactions through their complex enzymatic machinery, as well as the high susceptibility of halimane-diterpenoid substrates.


1   Institute of Chemistry, University of São Paulo – USP, CP 780, BR-13560970 Sao Carlos, SP – Brazil

2    Institute of Chemistry; São Paulo State University – UNESP; Nucleus of Bioassays, Biosynthesis and Ecophysiology of Natural Produtos – NuBBE; Department of Organic Chemistry; Francisco Degni 55, BR-14800900 Araraquara, SP – Brazil

3   Sao Carlos Institute of  Physics, University of Sao Paulo – USP, POB 369, BR-13556097 Sao Carlos, SP – Brazil

4   Instituto de  Ciencias Biomedicas, University of Sao Paulo – USP, Av Lineu Prestes 1524, BR-05508900 Sao Paulo, SP – Brazil


Link to article:   https://www.sciencedirect.com/science/article/pii/S0045206818312963?via%3Dihub