Microbiological oxygenation of acylated 1-adamantanamines. Stereochemistry and structural determinations

Herr, Milton E.; Johnson, Roy A.; Murray, H. C.; Reineke, L. M.; Fonken, Gunther S.

doi:10.1021/jo01272a037

Cited by 15 publications

(17 citation statements)

References 2 publications

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“…We think at this stage that the benzo-y-pyrone part of the molecule interacts with the binding site of the enzyme, possibly via the carbonyl group, and exposes ring B to the hydroxylating site of the microbial enzyme. The lack of hydroxylation of benzoylated azocycloalkanes, adamantanmines and hydroquinoline in the aromatic ring was also observed with incubations using Sporotiichum sulfurescens (Herr et al 1968, Johnson et al 1968a, 1968 b, 1 9 6 8~) 1969). Furthermore, our studies show that the 3',4'-dihydroxylated metabolites were formed by hydroxylation of the initially formed 4'-hydroxyflavonoids.…”

Section: Discussionmentioning

confidence: 81%

Microbiological transformation of flavone and isoflavone

Ibrahim

Abul-Hajj

1990

Xenobiotica

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1. Flavone and isoflavone were subjected to microbial transformation studies. Screening with 80 fungal species showed that flavone was transformed by a large number of microorganisms and in higher yields than isoflavone. 2. Large-scale fermentations of flavone followed by isolation and characterization of metabolites using spectroscopic analysis showed the formation of 4'-hydroxyflavone, 3',4'-dihydroxyflavone and two cleavage products identified as o-hydroxyphenyl-hydroxymethyl ketone and 1-(o-hydroxyphenyl)-1,2-ethanediol. However, fermentation of isoflavone gave only 4'-hydroxyisoflavone and 3',4'-dihydroxyisoflavone.

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Section: Discussionmentioning

confidence: 81%

Microbiological transformation of flavone and isoflavone

Ibrahim

Abul-Hajj

1990

Xenobiotica

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“…These were generated in greater quantities via a whole‐cell oxidation system. The two products were isolated in a pure form after extraction and silica gel chromatography (the products are highly soluble in aqueous solution) . These were identified as 4‐hydroxy‐N‐(1‐adamantyl)acetamide, 12 a , and 3‐hydroxy‐N‐(1‐adamantyl)acetamide, 12 b , using their NMR spectra (Scheme , Figure S5(k), Figure S5(l)).…”

Section: Resultsmentioning

confidence: 99%

“…The oxidation of adamantane derivatives is of great interest as they are building blocks for more complex drug molecules and polymers. Microbial oxidative biotransformations of adamantane, 1 , 2‐adamantanone, 4 , adamantanols, 2 and 3 , and related substrates including the acetate esters are possible using different bacteria, including Streptomyces, and fungi including Basidiomycota , Absidia cylindrospora and Beauveria (Sporotrichum ) sulfurescens . Certain P450 enzymes and their mutants have also been reported to oxidise adamantane based substrates including CYP101 A1 and CYP101D2 though at lower activities than the turnover of the esters reported here …”

Section: Discussionmentioning

confidence: 99%

The Use of Directing Groups Enables the Selective and Efficient Biocatalytic Oxidation of Unactivated Adamantyl C‐H Bonds

et al. 2016

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Adamantane, 1‐ and 2‐adamantanol and 2‐adamantanone, were poor substrates for the cytochrome P450 enzyme CYP101B1. The CYP101B1 catalysed oxidation of 1‐adamantyl methyl ketone, and methyl 2‐(1‐adamantyl acetate), were more active generating a majority of the 4‐hydroxy metabolite. Substrate engineering using acetate and isobutyrate ester directing groups significantly increased the affinity, activity and coupling efficiency of CYP101B1 for the esters compared to the parent adamantanols, resulting in enhanced product formation rates (720 to 1350 nmol.(nmol‐P450)−1.min−1). The majority of the turnovers were selective for C−H bond hydroxylation with 4‐hydroxy‐1‐adamantyl isobutyrate and the 5‐hydroxy‐2‐adamantyl esters being generated as the sole majority product, 97 %, with high total turnover numbers, ranging from 4130 to 16500. In addition N‐(1‐adamantyl)acetamide, was oxidised by CYP101B1 whereas 1‐adamantylamine, was not. Whole‐cell biocatalytic reactions were used to generate the products in good yield. Overall the use of ester protecting groups and the modification of the amine to an amide enabled the more efficient and selective biocatalytic oxidation of adamantane frameworks.

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“…The choice of the particular strains -Cunninghamella echinulata (American Type Culture Collection, ATCC 9244), Thammostylum (helicostylum) piriforme (ATCC 8992), Trametes (Pycnoporus) sanguinea (ATCC 14622), Trametes (Pycnoporus) cinnabarina (ATCC 14623), Sporotrichum sulfurescens (ATCC 7159), and Curvularia lunata (ATCC 12017) -was based on previous reports in the literature with respect to specific biotransformations. For example, T. (helicostylum) piriforme (ATCC 8992) is known for 14α-hydroxylations of steroids 14 and S. sulfurescens was used to hydroxylate monocyclic alcohols 15 , perhydroquinolines 16 , and N-acyladamantanamines 17 . In 1959 Holmlund and coworkers 18 observed hydroxylation of tetracycline derivatives by C. lunata, which is also known for hydroxylations of steroids 19 FIG.…”

Section: Discussionmentioning

confidence: 99%

Biotransformations of morphine alkaloids by fungi: N-demethylations, oxidations, and reductions

Chaudhary

Leisch

Moudrá

et al. 2009

Collect. Czech. Chem. Commun.

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Morphine alkaloids and some of its derivatives (morphine, codeine, thebaine, oripavine, hydrocodone, and oxycodone) were subjected to fermentations with six fungal strains. The alkaloids were transformed to a variety of products via biological oxidations, reductions, and oxidative demethylations. The strain Cunninghamella echinulata proved to be the most effective for demethylations of all of the above compounds, except for morphine. The time profile of the conversion of 3-[ 14 CH 3 ]thebaine to 3-[ 14 CH 3 ]northebaine by C. echinulata cultures was also determined.

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Microbiological oxygenation of acylated 1-adamantanamines. Stereochemistry and structural determinations

Cited by 15 publications

References 2 publications

Microbiological transformation of flavone and isoflavone

Microbiological transformation of flavone and isoflavone

The Use of Directing Groups Enables the Selective and Efficient Biocatalytic Oxidation of Unactivated Adamantyl C‐H Bonds

Biotransformations of morphine alkaloids by fungi: N-demethylations, oxidations, and reductions

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