Tapentadol的不对称合成的开题报告.docxVIP

Tapentadol的不对称合成的开题报告

Title:AsymmetricSynthesisofTapentadol

Introduction:

Tapentadolisapotentanalgesicmedicationusedtotreatmoderatetosevereacutepain.Itisacentrallyactingsyntheticanalgesicthathasbothnorepinephrinereuptakeinhibitionandμ-opioidreceptoragonismactivities.ThedrugismarketedunderthetradenameNucynta,anditschemicalstructureconsistsoftwostereoisomers,(R)-and(S)-tapentadol.Amongthetwostereoisomers,(R)-tapentadolpossessesmorepotentanalgesiceffectsrelativeto(S)-tapentadol.Inaddition,(R)-tapentadolhasalowerriskofabuseanddependencepotentialthanotheropioids.Consequently,itiscrucialtodevelopefficientmethodsfortheasymmetricsynthesisoftapentadoltoproduceits(R)-stereoisomerinhighyieldandpurity.

Objectives:

Themainobjectiveofthisresearchistodevelopanefficientandstraightforwardmethodfortheasymmetricsynthesisoftapentadol,whichyieldssignificantquantitiesof(R)-tapentadolinhighpurity.

Methodology:

Theasymmetricsynthesisoftapentadolcanbeachievedusingavarietyofchiralauxiliariesorcatalysts.SomeofthecommonlyusedchemicalcatalystsincludePd,Ru,andRh,amongothers.Alternativeapproachesinvolveusingchiralauxiliariessuchasenantiomericallypureaminoacids,forexample,L-prolineorL-tryptophan,whichcanselectivelygenerate(R)-or(S)-enantiomers.Inthisstudy,weproposetouseL-prolineasthechiralauxiliaryfortheasymmetricsynthesisoftapentadol.Thesyntheticprocedurewillinvolvethefollowingsteps;

Step1:AcylationofL-prolinewithasuitableacidchloride,suchas3,4-dimethoxybenzoylchloride.ThisstepformsanN-acyl-L-prolineintermediate.

Step2:Nucleophilicadditionoftheintermediatewiththeappropriatealkylatingagent(e.g.,R-phenylethylbromide)underbasicconditions,suchasKOH,formsthefinalproduct,(R)-tapentadol.

Step3:The(S)-enantiomercanbeobtainedusingasimilarproce