Details
| Original language | English |
|---|---|
| Pages (from-to) | 903-906 |
| Number of pages | 4 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 7 |
| Issue number | 7 |
| Publication status | Published - 8 Apr 1997 |
| Externally published | Yes |
Abstract
The synthesis and identification in biological samples of the 1-O-acyl glucuronide 6 of the antiinflammatory drug ML-3000 is described. Starting with D-glucuronic acid γ-lactone, 2,3,4-tris(tert.-butyldimethysilyl) glucuronic acid trichloroethylester 4 was prepared (in seven steps) and subsequently coupled. with 1 under Mitsunobu conditions. Deprotection, i.e. removal of the trichloroethoxy group with zinc dust and desilylation with hydrofluoric acid in acetonitrile afforded a mixture of α- and β-6 which could be separated by preparative HPLC. The abundance of 6 in bile and plasma samples obtained from animal studies with the cynomolgus monkey and the rabbit following repeated administration of 1 could be demonstrated by LC-electrospray MS analysis.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Medicine
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Biology
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmaceutical Science
- Pharmacology, Toxicology and Pharmaceutics(all)
- Drug Discovery
- Biochemistry, Genetics and Molecular Biology(all)
- Clinical Biochemistry
- Chemistry(all)
- Organic Chemistry
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In: Bioorganic and Medicinal Chemistry Letters, Vol. 7, No. 7, 08.04.1997, p. 903-906.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Synthesis and biological identification of the acyl glucuronide of the antiinflammatory drug ML-3000
AU - Kirschning, Andreas
AU - Ries, Monika
AU - Domann, Silvie
AU - Martin, Wolfgang
AU - Albrecht, Wolfgang
AU - Arnold, Peter
AU - Laufer, Stefan
N1 - Funding information: Support by the Fonds der Chemischen Industrie is gratefully acknowledged.
PY - 1997/4/8
Y1 - 1997/4/8
N2 - The synthesis and identification in biological samples of the 1-O-acyl glucuronide 6 of the antiinflammatory drug ML-3000 is described. Starting with D-glucuronic acid γ-lactone, 2,3,4-tris(tert.-butyldimethysilyl) glucuronic acid trichloroethylester 4 was prepared (in seven steps) and subsequently coupled. with 1 under Mitsunobu conditions. Deprotection, i.e. removal of the trichloroethoxy group with zinc dust and desilylation with hydrofluoric acid in acetonitrile afforded a mixture of α- and β-6 which could be separated by preparative HPLC. The abundance of 6 in bile and plasma samples obtained from animal studies with the cynomolgus monkey and the rabbit following repeated administration of 1 could be demonstrated by LC-electrospray MS analysis.
AB - The synthesis and identification in biological samples of the 1-O-acyl glucuronide 6 of the antiinflammatory drug ML-3000 is described. Starting with D-glucuronic acid γ-lactone, 2,3,4-tris(tert.-butyldimethysilyl) glucuronic acid trichloroethylester 4 was prepared (in seven steps) and subsequently coupled. with 1 under Mitsunobu conditions. Deprotection, i.e. removal of the trichloroethoxy group with zinc dust and desilylation with hydrofluoric acid in acetonitrile afforded a mixture of α- and β-6 which could be separated by preparative HPLC. The abundance of 6 in bile and plasma samples obtained from animal studies with the cynomolgus monkey and the rabbit following repeated administration of 1 could be demonstrated by LC-electrospray MS analysis.
UR - http://www.scopus.com/inward/record.url?scp=0031002781&partnerID=8YFLogxK
U2 - 10.1016/S0960-894X(97)00123-6
DO - 10.1016/S0960-894X(97)00123-6
M3 - Article
AN - SCOPUS:0031002781
VL - 7
SP - 903
EP - 906
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 7
ER -