Synthesis of Methyl 1-O-(4-Hydroxymethamphetaminyl)-.ALPHA.-D-glucopyranouronate

Nakajima, Rika; Ono, Masahiro; Aiso, Sadakazu; Akita, Hiroyuki

doi:10.1248/cpb.53.684

Cited by 19 publications

(17 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Synthesis of 5 from 3 through 4 (Scheme 2) was based on a reported procedure [3]. Acylation of 4 was completed within 14 h at rt, and 5 was precipitated by using brine/water in 76% yield as a mixture of anomers (35/65, α/β).…”

Section: Resultsmentioning

confidence: 99%

“…Stereoselective β-O-glycosylation of morphine that contains secondary alcohol and tertiary amine has also been reported under Koenigs-Knorr conditions [8]. Stereoselective β-O-glycosylation of a phenol containing a tertiary amine with α-O-trichloroacetimidate glycosyl donor has also been reported [3]. However, stereoselective β-O-glycosylation of a substrate that contains a tertiary alcohol and a secondary amine has not been reported in literature to the best of our knowledge.…”

Section: Introductionmentioning

confidence: 87%

“…Therefore, a multi-step synthesis of 2 was designed as shown below. Based on a retro-synthetic analysis (Scheme 1), 2 could be prepared via O-glycosylation of 1 with the corresponding glucuronic acid derivative 7, which could in turn be prepared from D-(+)-glucurono-6,3-lactone (3) using a published procedure [3]. The successful synthesis of 2 critically would rely on how the O-glycosylation of 1 with 7 is taken.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Synthesis of Vildagliptin-β-<i>O</i>-Glucuronide

Lu¹,

Liu²,

Prashad³

et al. 2012

ACES

View full text Add to dashboard Cite

A linear 7-step synthesis of vildagliptin-β-O-glucuronide (2) starting from commercially available D-glucurono-6,3-lactone (3) was herein achieved with 11.3% overall yield. Efficient preparation of compound 6 in pure α form was obtained, which was proved critical to achieve high anomeric selectivity in β-O-glycosylation later. The direct β-O-glycosylation of vildagliptin (1) containing both a tertiary alcohol and a secondary amine was studied and achieved in good yield. The deprotection step to afford product was delicately executed to avoid hydrolysis of nitrile group. The target compound 2 was obtained after purification by reversed-phase C18 chromatography.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis of Vildagliptin-β-<i>O</i>-Glucuronide

Lu¹,

Liu²,

Prashad³

et al. 2012

ACES

View full text Add to dashboard Cite

show abstract

“…9) Pholedrine, p-hydroxymethamphetamine (p-OHMA) and methamphetamine (MA) hydrochloride were obtained from Sigma (St. Louis, MO, U.S.A.) and Dainippon Pharmaceutical (Osaka, Japan), respectively (Fig. 1).…”

Section: Methodsmentioning

confidence: 99%

Direct Determination of p-Hydroxymethamphetamine Glucuronide in Human Urine by High-Performance Liquid Chromatography

Nakajima

Morishita

Aiso

et al. 2006

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

Drug abuse has recently become a serious worldwide problem and is increasing rapidly. Illicit drugs are stimulants, marijuana, cocaine, heroin and tranquilizers, among which methamphetamine (MA) is the most frequently abused drug in Japan. Arrests for violation of the Stimulant Drug Control Law are now on the verge of 20000/year. MA addiction is evidenced by the detection of unchanged MA as well as metabolite amphetamine (AP), thus MA analysis in urine samples has been employed routinely as a standard screening test using thin layer chromatography (TLC), 1) followed by gas chromatography/mass spectrometry (GC/MS).2) MA is metabolized either by hydroxylation of the aromatic ring or demethylation of the side chain. It has been reported that the metabolites of MA in urine were excreted as the unchanged (18-27%), free and conjugated forms of p-hydroxymethamphetamine (p-OHMA; 14-16%) and AP (2-3%) (Fig. 1). 3)It has been reported in the literature that the analysis of conjugated forms of p-OHMA in the urine samples of MA abusers used to be carried out by comparing the ratios of free p-OHMA to total p-OHMA before and after hydrolysis with b-glucuronidase or HCl treatment. [4][5][6][7][8] In the present paper, we describe the development and optimization of the method for the direct determination of intact p-OHMA glucuronide (p-OHMAG). Even in a case where the concentration of AP present in the urine is too low to be determined, it has been reported that the levels of p-OHMA and its conjugated form excreted in the urine were much higher than AP. We are thus convinced that a simultaneous determination of p-OHMAG, p-OHMA and MA in the urine of MA abusers could be unambiguous evidence of the ingestion of MA. ExperimentalMaterials and Reagents p-Hydroxymethamphetamine glucuronide (p-OHMAG) was synthesized from 4-hydroxyphenylacetic acid methyl ester according to the method developed in our laboratory.9) Pholedrine, p-hydroxymethamphetamine (p-OHMA) and methamphetamine (MA) hydrochloride were obtained from Sigma (St. Louis, MO, U.S.A.) and Dainippon Pharmaceutical (Osaka, Japan), respectively (Fig. 1). Sodium 1-dodecanesulfonate (ion pair grade) was purchased from Tokyo Kasei Kogyo (Tokyo, Japan). Methanol and acetonitrile were of HPLC grade, and all other reagents were of analytical grade.Standard solutions: the concentrations of a standard solution were set in the vicinity of the limits of quantification (LOQ). Stock solutions were prepared by dissolving appropriate amounts of p-OHMAG, p-OHMA and MA in distilled water and were kept frozen until use, then diluted appropriately prior to use.Distilled and deionized water prepared with Elix (Millipore, Tokyo) was used throughout this investigation.Sep-Pak ® Light C18 cartridges (reversed-phase monofunctional silane, 130 mg) were obtained from Waters Corp. (Milford, MA, U.S.A.).A drug free urine sample collected from a healthy subject in our laboratory was used to make blank and spiked urine samples containing standard solutions. The urine samples of MA abusers were obtained f...

show abstract

“…10, 12, 15 Brown et al 15 used a tri-Oisobutyryl protected trichloroacetimidate as glucuronidating agent. However, we found that use of the tri-O-acetyltrichloroacetimidate 3 16 provided the most practical route to useful Methyl (4-acetamidophenyl-2,3,4-tri-O-acetyl-β-D-glucopyranosid)uronate 4 was obtained using the glucuronide donor 3, paracetamol and BF 3 .OEt 2 in dichloromethane. Base hydrolysis of 4 was achieved using 2 equivalents of K 2 CO 3 in 5:5:1 MeOH:THF:H 2 O.…”

mentioning

confidence: 99%

Preparation and characterisation of solid state forms of paracetamol-O-glucuronide

Hayes

Eccles

Lawrence

et al. 2012

Carbohydrate Research

View full text Add to dashboard Cite

Synthesis of Methyl 1-O-(4-Hydroxymethamphetaminyl)-.ALPHA.-D-glucopyranouronate

Cited by 19 publications

References 6 publications

Synthesis of Vildagliptin-β-<i>O</i>-Glucuronide

Synthesis of Vildagliptin-β-<i>O</i>-Glucuronide

Direct Determination of p-Hydroxymethamphetamine Glucuronide in Human Urine by High-Performance Liquid Chromatography

Preparation and characterisation of solid state forms of paracetamol-O-glucuronide

Contact Info

Product

Resources

About

Synthesis of Methyl 1-O-(4-Hydroxymethamphetaminyl)-.ALPHA.-D-glucopyranouronate

Cited by 19 publications

References 6 publications

Synthesis of Vildagliptin-β-&lt;i&gt;O&lt;/i&gt;-Glucuronide

Synthesis of Vildagliptin-β-&lt;i&gt;O&lt;/i&gt;-Glucuronide

Direct Determination of p-Hydroxymethamphetamine Glucuronide in Human Urine by High-Performance Liquid Chromatography

Preparation and characterisation of solid state forms of paracetamol-O-glucuronide

Contact Info

Product

Resources

About

Synthesis of Vildagliptin-β-<i>O</i>-Glucuronide

Synthesis of Vildagliptin-β-<i>O</i>-Glucuronide