Total synthesis of (+/-)-kainic Acid with an aza-[2,3]-Wittig sigmatropic rearrangement as the key stereochemical determining step.
A flexible route to the kainoid skeleton is exemplified by the synthesis of (+/-)-kainic acid from 3-butyn-1-ol. The route relies on the aza-[2,3]-Wittig sigmatropic rearrangement to efficiently install the relative stereochemistry between C2-C3. The C4 stereocenter was derived from a diastereocontrolled iodolactonization. The aza-[2,3]-Wittig rearrangement potentially allows structural diversity at C3 and the displacement of the tosyloxy group with retention of stereochemistry allows structural diversity at C4. The trans-C2 carboxylic acid functional group was found to be the most important for retention of stereochemistry at C4 upon treatment with a higher order cyano cuprate reagent.
Anderson
James C
JC
School of Chemistry, University of Nottingham, Nottingham, NG7 2RD, UK. j.anderson@nottingham.ac.uk
Whiting
Matthew
M
D000478:Alkylation; D001372:Aza Compounds / Q000138:chemical synthesis; D018690:Excitatory Amino Acid Agonists / Q000138:chemical synthesis*; D006900:Hydroxylation; D006909:Hydroxyproline / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D007202:Indicators and Reagents; D007608:Kainic Acid / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D013237:Stereoisomerism
C008051:3-hydroxy-4-methylproline; D001372:Aza Compounds; D018690:Excitatory Amino Acid Agonists; D007202:Indicators and Reagents; D006909:Hydroxyproline; D007608:Kainic Acid