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Model Studies on Peroxidic Glutathione Transferase (GST) Inhibitors: C5‐Methylated 1,2,4‐Trioxanes with C6‐Acrylate Side Chains
Author(s) -
Griesbeck Axel G.,
Maaßen Andreas,
Bräutigam Maria,
Pietsch Markus
Publication year - 2015
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201500326
Subject(s) - chemistry , trioxane , catalysis , substrate (aquarium) , singlet oxygen , glutathione , allylic rearrangement , lewis acids and bases , side chain , porphyrin , medicinal chemistry , organic chemistry , stereochemistry , oxygen , enzyme , polymerization , geology , polymer , oceanography
Abstract The 1,2‐hydroxy hydroperoxide 7 was obtained with high threo diastereoselectivity from the ester‐conjugated allylic alcohol 6 through a porphyrin‐sensitized singlet oxygen ene reaction. Compound 7 was used as substrate for peroxy(trans)acetalization with aldehydes, orthoesters, and acetals, catalyzed by boron and indium Lewis acids, as well as by PPTS as a Brønsted acid catalyst (for trioxane 10 ). The 1,2,4‐trioxane 8 was formed with high diasteroselectivity with all‐equatorially positioned substitutents at C‐3, C‐5, and C‐6. Additionally, perorthoester 9 was obtained by indium(III)‐catalyzed condensation of an orthoester with the hydroperoxide 7 . The new compounds 8 and 9 exhibited moderate inhibition of human placental glutathione transferase (GST), comparable to that shown by the 5‐unsubstituted model trioxane 11 .