Becauseawidearrayofnitrogen-??containingcompoundsexhibitbioactivity,thedevelopmentofnew methodsfortheformationofC?Nbondsisacentralchallengeinorganicchemistry.Furthermore, becausethetwomirror-??imageisomers(?enantiomers?)ofamoleculegenerallyhavedifferentbiological activityduetothe?handedness?ofthemoleculesoflife(e.g.,peptides,DNA,RNA,andcarbohydrates), thereisaneedinthebiomedicalcommunitytoefficientlygeneratecompoundsinstereoisomericallypure form.Finally,thedevelopmentofcatalyzedreactionsisdesirable,sincetheyoftenofferadvantagesfrom thestandpointsofefficiency/economy. Thisproposalisdirectedataddressingallthreeofthesechallenges,specifically,thediscoveryofnew methodsforthecatalyticandenantioselectivesynthesisofnitrogen-??containingcompounds.Inparticular, theresearchplandescribesthedevelopmentofthefirstphotoinduced,copper-??catalyzedmethodsforthe constructionofC?Nbonds.Thecouplingreactionsareanticipatedtoproceedunderunusuallymild conditions,tohavebroadapplicabilityforthegenerationofdiversefamiliesofnitrogen-??containing compounds,andtoproceedwithgoodstereoselectivity(whenapplicable).Furthermore,theresearch plandescribesmechanisticstudies(e.g.,stereochemical,massspectrometry,fluorometry,andelectron paramagneticresonancespectroscopy)thatwillprovideinsightintotheunusualreactionpathwayof thesephotoinduced,copper-??catalyzedC?Nbond-??formingreactions,whichlikelyproceedthrougha radicalintermediate.

Public Health Relevance

/RELEVANCE Thedevelopmentofefficientnewchemicalprocesseshasanimpactonawidearrayofdisciplinesthat requirethesynthesisoforganiccompounds(e.g.,biologicalchemistry,pharmaceuticalchemistry,and biology).Nitrogen-??containingcompoundshaveahighpropensitytobebioactive(e.g.,AbilifyTM, CrestorTM,CymbaltaTM,LipitorTM,NexiumTM,andPlavixTM);consequently,thediscoveryofnovel approachestothesynthesisofnitrogen-??containingcompounds,whichisthefocusofthisproposal,isan importantendeavorforthebiomedicalcommunity.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM109194-05S1
Application #
9743598
Study Section
Program Officer
Lees, Robert G
Project Start
2014-05-15
Project End
2022-05-31
Budget Start
2018-07-01
Budget End
2019-05-31
Support Year
5
Fiscal Year
2019
Total Cost
Indirect Cost
Name
California Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
009584210
City
Pasadena
State
CA
Country
United States
Zip Code
91125
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