A concise and scalable synthesis of high enantiopurity (-)-D-erythro-sphingosine using peptidyl thiol ester-boronic acid cross-coupling.
A short and efficient synthesis of high enantiopurity (-)-D-erythro-sphingosine has been achieved in 71% yield over 6 steps from N-Boc-L-serine. The key steps are high yield, racemization-free, palladium-catalyzed, copper(I)-mediated coupling of the thiophenyl ester of N-Boc-O-TBS L-serine with E-1-pentadecenyl boronic acid and the highly diastereoselective reduction of the resulting peptidyl ketone with LiAl(O-t-Bu)3H. By using this concise route (-)-D-erythro-sphingosine can be prepared on large scale and in high enantio- and diastereopurity (ee >99%, de up to 99%).
Yang
Hao
H
Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, USA.
Liebeskind
Lanny S
LS
D001897:Boronic Acids / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D004952:Esters; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry; D012694:Serine / Q000031:analogs & derivatives* / Q000737:chemistry; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D001897:Boronic Acids; D004952:Esters; D013438:Sulfhydryl Compounds; C481931:erythro-(2R,3S)-sphingosine; D012694:Serine; D010165:Palladium; D003300:Copper; D013110:Sphingosine