Synthesis and biological activity of derivatives of ubiquinone: photoaffinity analogues containing the 4-azido-2-nitroanilino group.
The photoaffinity analogues of ubiquinone 2,3-dimethoxy-5-methyl-6-[2-[1-oxo-3-(4-azido-2-nitroanilino) propoxy]-3-methylbutyl]-1,4-benzoquinone (2'-ANAP-Q-1) and 2,3-dimethoxy-5-methyl-6-[3-[1-oxo-3-(4-azido-2-nitroanilino) propoxy]-3-methylbutyl]-1,4-benzoquinone (3'-ANAP-Q-1) have been synthesized. The required intermediate alcohols 2,3-dimethoxy-5-methyl-6-(2-hydroxy-3-methylbutyl)-1,4-benzoquinone and 2,3-dimethoxy-5-methyl-6-(3-hydroxy-3-methylbutyl)-1,4-benzoquinone were prepared in good yield from ubiquinone 1 by hydration of the side-chain double bond via hydroboration or acid catalysis, respectively. These alcohols were then coupled with 3-(4-azido-2-nitroanilino)propanoic acid, with p-toluenesulfonyl chloride in dry pyridine, to give 2'- and 3'-ANAP-Q-1. The synthetic methods presented should be of general utility in the preparation of derivatives of ubiquinone in which a reactive or reporter group is relatively close to the ubiquinone ring. By use of membrane vesicles prepared from a ubi-men-strain of Escherichia coli described previously [Wallace, B., & Young, I. G. (1977) Biochim. Biophys. Acta 461, 84-100], it has been shown that 2'- and 3'-ANAP-Q-1 substitute for ubiquinone 8 in the NADH, succinate, and D-lactate oxidase systems. Thus, these compounds may be of value in labeling respiratory chain proteins that interact with ubiquinone.
Campbell
H D
HD
Rogers
B L
BL
Young
I G
IG
D000345:Affinity Labels / Q000138:chemical synthesis*; D004926:Escherichia coli / Q000201:enzymology; D007202:Indicators and Reagents; D007700:Kinetics; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases / Q000378:metabolism; D013329:Structure-Activity Relationship; D014451:Ubiquinone / Q000031:analogs & derivatives*
D000345:Affinity Labels; D007202:Indicators and Reagents; D014451:Ubiquinone; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases