文摘
Two candidate photoaffinity probes are designed from 4-substitutedquinazolines known tobe potent insecticides/acaricides and NADH:ubiquinone oxidoreductaseinhibitors acting at ornear the rotenone site.4-(11-Azidoundecyl-2-amino)quinazoline, based on theundecylaminoanalog SAN 548A as a prototype, was synthesized in 18% overall yieldfrom ethyl 10-undecenoate by oxidation of the terminal double bond, reductiveamination, coupling to4-chloroquinazoline, and functional group manipulation of the terminalethyl ester to an alcohol,a mesylate and finally nucleophilic displacement with azide ions.4-(4-(3-(Trifluoromethyl)-3H-diazirin-3-yl)phenethoxy)quinazoline [the(trifluoromethyl)diazirinyl analog of fenazaquininsecticide/acaricide] was prepared from 4-bromophenethyl alcohol in31% overall yield by firstintroducing the trifluoromethylketone moiety followed by its conversionto the (trifluoromethyl)diazirine and finally coupling to 4-chloroquinazoline as above.Both candidate photoaffinityprobes have the inhibitory potency of rotenone (IC50 of3-4 nM in each case). Theazidoundecylamino compound has inadequate photoreactivity whereas thatof the (trifluoromethyl)diazirinyl analog is ideal at 350 nm. Radiosynthesis ofthe latter photoaffinity ligandincluded introduction of the diazirinyl moiety as the carbeneprecursor, oxidation of (trifluoromethyl)diazirinylphenethyl alcohol to the corresponding acid withJones' reagent, andreduction of the phenacetyl chloride intermediate with sodiumborotritide to incorporate tritium.
