A convenient new synthesis of quaternary ammonium glucuronides of drug molecules

Iddon, Lisa; Bragg, Ryan A.; Harding, John; Stachulski, Andrew V.

doi:10.1016/j.tet.2009.10.113

Cited by 7 publications

(11 citation statements)

References 32 publications

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“…As such, the work put forth further expands the substrate scope and synthetic potential of enhanced OleDs and presents a complement to conventional synthetic strategies to access quaternary amino-N-glycosides. [11] …”

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confidence: 99%

“…Likewise, although sugar conjugation is known to influence small-molecule mechanisms, potency, and ADMET, [1a, e, 20] a lack of practical synthetic or chemoenzymatic access has limited studies to probe the fundamental properties of quaternary N-glycosides. [10,11] Our discovery offers a convenient new model for GT-catalyzed tertiary-amine N-glycosylation and a potential complementary synthetic platform for efficient one-step synthesis of quaternary N-glycosides. In a similar fashion, the discovery that OleD Loki is an efficient catalyst for hydroxamate glycosyl ester synthesis further extends the demonstrated synthetic utility of this permissive catalyst.…”

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confidence: 99%

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OleD Loki as a Catalyst for Tertiary Amine and Hydroxamate Glycosylation

et al. 2017

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We describe the ability of an engineered glycosyltransferase (OleD Loki) to catalyze the N-glycosylation of tertiary-amine-containing drugs and trichostatin hydroxamate glycosyl ester formation. As such, this study highlights the first bacterial model catalyst for tertiary-amine N-glycosylation and further expands the substrate scope and synthetic potential of engineered OleDs. In addition, this work could open the door to the discovery of similar capabilities among other permissive bacterial glycosyltransferases.

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confidence: 99%

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OleD Loki as a Catalyst for Tertiary Amine and Hydroxamate Glycosylation

et al. 2017

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“…The successful preparation of zwitterionic [ 13 CD 3 ]‐asenapine N + ‐glucuronide 28 is shown in Scheme and began with N ‐desmethylasenapine 4 . Because of the potential of transacylation with acylated hemiacetals, glucuronidation of 4 was best accomplished with triisobutyl hemiacetal 26 . Reaction of 26 in toluene at 50 °C for 18 h gave 27 in near quantitative yield.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of stable isotope‐labeled metabolites of asenapine

Kuethe

2012

Labelled Comp Radiopharmac

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The stable isotope‐labeled synthesis of four of the major metabolites of asenapine is described. The synthesis of [13CD3]‐asenapine N‐oxide proceeded in two synthetic steps. Preparation of [13CD3]‐asenapine 11‐hydroxysulfate and [13C6]‐N‐desmethylasenapine paralleled established synthetic protocols with effective utilization of labeled precursors. The synthesis of [13CD3]‐asenapine N+‐glucuronide was achieved in three chemical steps followed by purification.

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“…Hence, the biosynthetic method presented in this paper shows a viable alternative to isolation from a biological matrix for the generation of an N + -glucuronide, should further pharmacological assessments be required. Recent literature has also demonstrated advances in purely synthetic approaches to the production of quarternary N + -glucuronides [18].…”

Section: Structural Characterisation Of Human Metabolite M3 By 1 H Nmmentioning

confidence: 99%