18374-79-3Relevant academic research and scientific papers
Enzymatic hydroxylation of an unactivated methylene C-H bond guided by molecular dynamics simulations
Narayan, Alison R. H.,Jimnez-Oss, Gonzalo,Liu, Peng,Negretti, Solymar,Zhao, Wanxiang,Gilbert, Michael M.,Ramabhadran, Raghunath O.,Yang, Yun-Fang,Furan, Lawrence R.,Li, Zhe,Podust, Larissa M.,Montgomery, John,Houk,Sherman, David H.
, p. 653 - 660 (2015)
The hallmark of enzymes from secondary metabolic pathways is the pairing of powerful reactivity with exquisite site selectivity. The application of these biocatalytic tools in organic synthesis, however, remains under-utilized due to limitations in substrate scope and scalability. Here, we report how the reactivity of a monooxygenase (PikC) from the pikromycin pathway is modified through computationally guided protein and substrate engineering, and applied to the oxidation of unactivated methylene C-H bonds. Molecular dynamics and quantum mechanical calculations were used to develop a predictive model for substrate scope, site selectivity and stereoselectivity of PikC-mediated C-H oxidation. A suite of menthol derivatives was screened computationally and evaluated through in vitro reactions, where each substrate adhered to the predicted models for selectivity and conversion to product. This platform was also expanded beyond menthol-based substrates to the selective hydroxylation of a variety of substrate cores ranging from cyclic to fused bicyclic and bridged bicyclic compounds.
Hydroxylation of (+)-menthol by Macrophomina phaseolina
Musharraf, Syed Ghulam,Ahmed, Muhammad Arif,Ali, Rahat Azher,Choudhary, Muhammad Iqbal
experimental part, p. 77 - 82 (2012/04/11)
Biotransformation of (+)-menthol with Macrophomina phaseolina led to hydroxylations at C-1, C-2, C-6, C-7, C-8 and C-9, with the C-8 position being preferentially oxidized. The resulting metabolites were identified as 8-hydroxymenthol (2), 6R-hydroxymenthol (3), 1R-hydroxymenthol (4), 9-hydroxymenthol (5), 2R,8-dihydroxymenthol (6), 8S,9-dihydroxymenthol (7), 6R,8-dihydroxymenthol (8), 1R,8-dihydroxymenthol (9) and 7,8-dihydroxymenthol (10). Metabolites 6-10 are described here for the first time. Their structures were characterized by spectroscopic analysis.
Fungal transformation of (1R,2S,5R)-(-)-menthol by Cephalosporium aphidicola
Atta-ur-Rahman,Yaqoob, Muhammad,Farooq, Afgan,Anjum, Shazia,Asif, Fahim,Choudhary, M. Iqbal
, p. 1340 - 1342 (2007/10/03)
Incubation of (1R,2S,5R)-(-)-menthol (1) with Cephalosporium aphidicola for 12 days yielded the six oxidized metabolites: 10-acetoxymenthol (2), 7- hydroxymenthol (3), 4α-hydroxymenthol (4), 3α-hydroxymenthol (5), 9- hydroxymenthol (6), and 10-hydroxymenthol (7). The structures of the novel compounds 2, 4, 5, and 7 were assigned by interpretation of their spectral data.
