Amidoximes and Oximes: Synthesis, Structure, and Their Key Role as NO Donors.

Tanya Sahyoun,Raphaël Schneider,Axelle Arrault

doi:10.3390/molecules24132470

Abstract

Nitric oxide (NO) is naturally synthesized in the human body and presents many beneficial biological effects; in particular on the cardiovascular system. Recently; many researchers tried to develop external sources to increase the NO level in the body; for example by using amidoximes and oximes which can be oxidized in vivo and release NO. In this review; the classical methods and most recent advances for the synthesis of both amidoximes and oximes are presented first. The isomers of amidoximes and oximes and their stabilities will also be described; (Z)-amidoximes and (Z)-oximes being usually the most energetically favorable isomers. This manuscript details also the biomimetic and biological pathways involved in the oxidation of amidoximes and oximes. The key role played by cytochrome P450 or other dihydronicotinamide-adenine dinucleotide phosphate (NADPH)-dependent reductase pathways is demonstrated. Finally, amidoximes and oximes exhibit important effects on the relaxation of both aortic and tracheal rings alongside with other effects as the decrease of the arterial pressure and of the thrombi formation

Highlights

IntroductionOximes and amidoximes (oximes in which one of the substituents is an amino grouIpn) r(eFcigenutreye1a) rhsa, voexigmaeinseadndhiagmh iidnotexriemste.s T(ohxeisme ecsominpwouhincdhsoanree oufsuthaellysuebasstyitutoenstysnitshaensizaemainndo gwreorueps)tu(Fdiigeudrien1m) ahnayvedigffaeirneendt fiheigldhs isnutcehreasst.cTohoerdseincaotimonpo[1u]nodrsmaareteurisaulsalclhyeemaissytrtyo[2sy,3n]tbhuestiazlesoanfodr wtheerier nsutumdeieroduisnbmioalongyicdailffaecrteivnittifeies.ldMs osruecohvears, tchoeoradminidaotixoinm[e1f]uonrctmioanteirsiaolfstecnhuemseidstarsyb[i2o,3is]obsutetraolfsoa fcoarrbthoexiyrlnicuamciedr,oaunsdbitohleorgeicaarel ascotmiveitsieusc.cMesosrfeuol veexra,mthpeleasmoifddorxuimg ecafnudnicdtiaotnesisexohftiebnituinsgedcaarsdbioiotoisnoiscteorr oafnaticaartrhbroixtiyclpicraocpiedr,taiensdctohnetraeinairnegsothmeeasmucidceosxsifmuel emxaomieptyl.es of drug candidates exhibiting cardiotonic or antiarthritic properties containing the amidoxime moiety
Amidoximes and oximes have poorly been studied in the literature regarding their isomerism
Many cytochrome P450 (CYP450) isoforms have been identified as responsible of the oxidations of these products like CYP4501A1, CYP4502B1, and CYP4502E1 [5,63]. These results demonstrate that NOS are not optimal for the evaluation of the NO release from amidoximes

Summary

Introduction

Oximes and amidoximes (oximes in which one of the substituents is an amino grouIpn) r(eFcigenutreye1a) rhsa, voexigmaeinseadndhiagmh iidnotexriemste.s T(ohxeisme ecsominpwouhincdhsoanree oufsuthaellysuebasstyitutoenstysnitshaensizaemainndo gwreorueps)tu(Fdiigeudrien1m) ahnayvedigffaeirneendt fiheigldhs isnutcehreasst.cTohoerdseincaotimonpo[1u]nodrsmaareteurisaulsalclhyeemaissytrtyo[2sy,3n]tbhuestiazlesoanfodr wtheerier nsutumdeieroduisnbmioalongyicdailffaecrteivnittifeies.ldMs osruecohvears, tchoeoradminidaotixoinm[e1f]uonrctmioanteirsiaolfstecnhuemseidstarsyb[i2o,3is]obsutetraolfsoa fcoarrbthoexiyrlnicuamciedr,oaunsdbitohleorgeicaarel ascotmiveitsieusc.cMesosrfeuol veexra,mthpeleasmoifddorxuimg ecafnudnicdtiaotnesisexohftiebnituinsgedcaarsdbioiotoisnoiscteorr oafnaticaartrhbroixtiyclpicraocpiedr,taiensdctohnetraeinairnegsothmeeasmucidceosxsifmuel emxaomieptyl.es of drug candidates exhibiting cardiotonic or antiarthritic properties containing the amidoxime moiety. Amidoximes and oximes have poorly been studied in the literature regarding their isomerism. Acc3o.1r.dSinyngthteosisthofeAlmitiedroaxtimuerse, amidoximes and oximes are compounds synthesized in high yields. The attack of hydroxylamine on nitriles is the mostly used method since Tiemann showed that mixing a nitrile with hydroxylamine hydrochloride and sodium carbonate in an alcohol produces the corresponding amidoxime after several hours of heating at 60–80 °C [31]. Via this method, amidoximes are generally prepared in high yield, up to 98% (entry 1) [32]. Amidoximes were obtained in lower yields (35–63%) after passing 1-alkoxyadenine derivatives through Amberlite IRA 402 column and heating the eluate at 30–40◦C for 7–48 h [48]

Synthesis of Oximes

Oxidation by Chemicals and Biomimetics

Findings

Conclusions