Biocatalytic Synthesis of Chiral 1,2,3,4-Tetrahydroquinolines
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
Pioneering work goes back to 1985 when Crabb and co-workers reported about the fungus Cunninghamella elegans-catalyzed transformation of 1,2,3,4-tetrahydroquinoline, which produced N-benzoyl-1,2,3,4-tetrahydroquinolin-4-ol mystically (Crabb and Soilleux, 1985). The authors found that benzylic oxidation attacks C4 of the substrates to give further oxidized N-acetyl-1,2-dihydroquinolin-4(3H)-one as the only product after incubation of N-acetyl-1,2,3,4-tetrahydroquinoline with C. elegans cell strain. In principle, oxidation could occur at C4 in the heterocyclic ring and the methyl group in the toluoyl moiety with N-p-toluoyl-1,2,3,4-tetrahydroquinoline as the substrate; however, the highly selectively reaction occurred at C4 position to give N-(p-toluoy1)-1,2-dihydroquinolin-4(3H)-one as the only product, too. Surprisingly N-benzoyl-1,2,3,4-tetrahydroquinoline after incubation with C. elegans gave a mixture of N-benzoyl-1,2-dihydroquinolin-4(3H)-one 2c and N-benzoyl-1,2,3,4-tetrahydroquinolin-4-ol 3c in low yields, which shows that the reaction can be controlled in the first oxidation step (Scheme 19.1). Transformation of N-substituted THQs catalyzed by C. elegans cells.
Biotransformation of Sesquiterpenoids, Ionones, Damascones, Adamantanes, and Aromatic Compounds by Green Algae, Fungi, and Mammals
K. Hüsnü Can Başer, Gerhard Buchbauer in Handbook of Essential Oils, 2020
Twenty strains of filamentous fungi and four species of bacteria were screened initially by thin-layer chromatography for their biotransformation capacity of curdione (120). Mucor spinosus, Mucor polymorphosporus, Cunninghamella elegans, and Penicillium janthinellum were found to be able to biotransform curdione (120) to more polar metabolites. Incubation of curdione with M. spinosus, which was most potent strain to produce metabolites, for 4 days using potato medium gave five metabolites (134, 134a–134d) among which compounds 134c and 134d are new products (Ma et al., 2006) (Figure 23.46).
In silico molecular docking for assessing anti-fungal competency of hydroxychavicol, a phenolic compound of betel leaf (Piper betle L.) against COVID-19 associated maiming mycotic infections
Published in Drug Development and Industrial Pharmacy, 2022
Vinusri Sekar, Gnanam Ramasamy, Caroline Ravikumar
The virtual screening of the current recommended approved anti-fungal drugs for mycotic infections exhibited more binding affinity with the target Lanosterol 14 alpha demethylase of different fungal pathogens associated with COVID-19 infections, thereby assuring their anti-fungal efficacy. But, while considering their reported side effects and ADME profiling results, it was obvious that there is still a greater demand for safer and effective therapy for treating COVID-19 associated fungal infections. In the current study, the ADME profiling of the phytochemical hydroxychavicol ensured its drug- likeliness behavior besides its interaction with the target protein (Lanosterol 14 alpha demethylase) of nine different COVID-19 associated different opportunistic fungal pathogens such as Candida sp. (C. albicans, C. glabrata and C. tropicalis), Aspergillus fumigatus, Mucor sp. (Mucor circinelloides, Cunninghamella elegans and Rhizopus microsporus), Cryptococcus neoformans and Histoplasma capsulatum. The obtained results suggested the possibility of employing the hydroxychavicol in the treatment of COVID-19 associated mycotic infections. As per the reports mentioned earlier, the attempts can be realized based on the synergistic mode of treatment for mycotic infections by using already approved antifungal drugs and hydroxychavicol. In such cases, further drug–drug interaction studies have to be performed between the antifungal drugs and hydroxychavicol. This synergistic approach may lessen the possibility of incidence of side effects due to drugs and even may enhance the antifungal efficacy of drugs. Thus, the present preliminary study may direct the research attention on the phytochemical hydroxychavicol for treating COVID-19 associated fungal infections.
Oxidative biotransformation of stemofoline alkaloids
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2021
Manlika Phaya, Sirinrat Chalom, Kornkanok Ingkaninan, Kontad Ounnunkad, Nopakarn Chandet, Stephen G. Pyne, Pitchaya Mungkornasawakul
Cunninghamella elegans TISTR3370 was provided by the Thailand Institute of Scientific and Technological Research (TISTR). Microbial cultures were maintained on potato dextrose agar slants at 4 °C and transferred every 6 months to maintain viability. Prior to biotransformation, the fungus was precultivated on PDA in Petri dishes for 3 days at 30 °C.
Microbial biotransformation – an important tool for the study of drug metabolism
Published in Xenobiotica, 2019
Rhys Salter, Douglas C. Beshore, Steven L. Colletti, Liam Evans, Yong Gong, Roy Helmy, Yong Liu, Cheri M. Maciolek, Gary Martin, Natasa Pajkovic, Richard Phipps, James Small, Jonathan Steele, Ronald de Vries, Headley Williams, Iain J. Martin
The following strains are referred to in the Results section in terms of their ability to produce the targeted metabolites: SP7001 (Amycolatopsis sp.), SP7015 (Ascomycete fungus) SP7043 (Amycolatopsis lurida), SP7045 (Streptomyces sp.), SP7049 (Streptomyces rimosus), SP7050 (Streptomyces peucetius), SP7059 (Streptomyces sp.), SP7074 (Cunninghamella elegans). Compounds (6a) and (8a) underwent production-scale biotransformation to produce metabolites for purification that had been positively matched by LC-MS/MS comparison of screen-scale samples with a chemically synthesized standard (6b) or a biological reference sample (8b). Where multiple strains were deemed capable of producing a target metabolite, strain selection was made according to the yield of conversion to the target metabolite, as well as an assessment of the complexity of metabolite purification, e.g. taking the presence of any co-eluting endogenous products or non-target co-produced metabolites into consideration. Additionally, a pre-scaling confirmation step was performed to check reproduction of screening-scale results in shake-flasks, with the inclusion of a 48 h seed culture stage. Scaled-up reproduction was achieved by performing the biotransformation reactions in a sufficient number of 250 mL Erlenmeyer flasks containing 50 mL working volumes, inoculated from seed cultures prepared as used in the confirmation step. The simplicity of this approach is designed to negate potential transfer issues, a well-known liability associated with transferring processes from shaken flasks to stirred tank bioreactors. The required volume for the scaled-up biotransformation was estimated based on an approximation of the yield of conversion from the confirmation step. In the cases reported herein, the scale-up reactions were repeated at two and 6 L volumes to provide sufficient material from which a range of 5–50 mg of target metabolites at >90% purity could be obtained using the processing methods described below. Metabolite (7b) was purified directly from screening-derived materials.
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