Development of optically pure pyrethroid-like fluorescent substrates for carboxylesterases

Huang, Huazhang, Stok, Jeanette E., Stoutamire, Donald W., Gee, Shirley J. and Hammock, Bruce D. (2005) Development of optically pure pyrethroid-like fluorescent substrates for carboxylesterases. Chemical Research in Toxicology, 18 3: 516-527. doi:10.1021/tx049773h

Author Huang, Huazhang
Stok, Jeanette E.
Stoutamire, Donald W.
Gee, Shirley J.
Hammock, Bruce D.
Title Development of optically pure pyrethroid-like fluorescent substrates for carboxylesterases
Journal name Chemical Research in Toxicology   Check publisher's open access policy
ISSN 0893-228X
Publication date 2005
Year available 2005
Sub-type Article (original research)
DOI 10.1021/tx049773h
Volume 18
Issue 3
Start page 516
End page 527
Total pages 12
Place of publication Washington D.C., U.S.A
Publisher American Chemical Society
Language eng
Subject 03 Chemical Sciences
0305 Organic Chemistry
0304 Medicinal and Biomolecular Chemistry
Abstract Pyrethroids are now the world's most extensively used insecticides. One of the common metabolic routes of pyrethroid insecticides in living systems is hydrolysis by carboxylesterases, and this hydrolysis may be stereospecific since most pyrethroid insecticides have chiral centers. In previous studies, pyrethroid-like fluorescent substrates have been shown to be hydrolyzed in a fashion similar to actual pyrethroids. It is important to synthesize the stereoisomers of pyrethroid-like fluorescent substrates to study the stereointeraction between carboxylesterases and these substrates. In this study, an effective synthetic method for preparing optically enriched (R)- and (S)-α-2-hydroxy-2-(6-methoxy-2-naphthyl)acetonitrile was developed. With this alcohol, an efficient synthetic route for preparation of optically pure cypermethrin and fenvalerate analogues was provided. Identification of these stereoisomers was determined based on GC, HPLC, 1H NMR, and X-ray crystallography. In addition, stereointeraction between carboxylesterases and chiral fluorescent substrates indicated that (i) stereospecificity of recombinant mouse liver carboxylesterases (NCBI accession nos. BAC36707 and NM_133960) varied significantly (up to 300-fold difference) with different stereoisomers of cypermethrin and fenvalerate analogues; (ii) on the basis of Vmax, the sensitivity of this analytical method, using a single stereoisomer of cypermethrin analogues instead of a mixture of eight stereosiomers, could be enhanced by 4−6 times for detection of these carboxylesterases; and (iii) possible usage of these carboxylesterases for chiral synthesis is discussed.
Keyword Pyrethroids
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Chemistry and Molecular Biosciences
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