Part I. Synthesis of cytochrome P450-CAM substrate analogues towards developing cytochrome P450-CAM as an enzyme-based model system for mechanistic studies of important types of P450 reactions. Part II. Diels-Alder approach towards the synthesis of 2,3-disubstituted anthracene derivatives for luminescence spectroscopy characterization: Synthesis towards fluorescent sensors.

摘要

Part I. Camphor analogues in which the normal site of hydroxylation is modified have been prepared in an effort to develop cytochrome P450-CAM as a versatile, enzyme-based model system for mechanistic studies of important types of P450 reactions. The (1R)-5-exo-methoxycamphor (2--15a) camphor analogue has been prepared to examine O-dealkylation by P450-CAM. The camphor analogues, 1-((8-iodooctylthio)methyl)-7,7-dimethylbicyclo[2.2.1]heptan-2-one (3--15) and 1-((10-iodooctylthio)methyl)-7,7-dimethyl-bicyclo[2.2.1]heptan-2-one (3--17), have been prepared for coupling to a bipyridine derivative in an effort to deliver electrons to the heme iron center by photoinjection. The (1R)- and (1S)-5-oximecamphor (4--7) analogues have been synthesized to investigate the mechanism in the second step in the synthesis of the essential biomolecule nitric oxide (NO·) in which NO· is produced from NG-hydroxy-L-arginine by nitric oxide synthase. Preliminary evidence with (1R)-5-oximecamphor suggests that the reactive intermediate for P450-CAM catalysis has been changed from compound I to possibly the ferric-hydroperoxide species.;Part II. Recently, we have investigated the fluorescent aromatic compound anthracene as a possible chemical dye. The Diels-Alder approach has been examined for formation of 2,3-disubstituted anthracene derivatives that have the potential to be tethered to a fiber optic. The desired Diels-Alder adduct 30 was prepared by reaction of diester diene 29 and 1,4-naphthoquinone. The Diels-Alder adduct was readily converted into the "tetherable" anthracene derivative, monoester 34. Luminescent spectroscopy indicated that 34 has maintained the basic fluorescent properties of the anthracene upon derivatization.