Synthesis of Thienamycin methyl ester from 2-deoxy-D-ribose via Kinugasa reaction.
A novel synthesis of thienamycin is described. The crucial step of the synthesis is based on Cu(I)-mediated Kinugasa cycloaddition/rearrangement cascade reaction between terminal acetylene derived from D-lactic acid and suitable, partially protected, five-membered cyclic nitrone obtained from 2-deoxy-D-ribose. The reaction was performed in the presence of tetramethylguanidine as a base to provide 5,6-trans substituted carbapenam as the main product. Thus obtained carbapenam 11 with (5R,6S) configuration at the azetidinone ring was subsequently subjected to oxidation/deprotection/oxidation reaction sequence to afford the β-keto ester 20, which was directly transformed into N,O-protected methyl ester of thienamycin.
Institute of Organic Chemistry of Polish Academy of Sciences, Warsaw, Poland.
Magdalena
M
Soluch
Institute of Organic Chemistry of Polish Academy of Sciences, Warsaw, Poland.
Barbara
B
Grzeszczyk
Institute of Organic Chemistry of Polish Academy of Sciences, Warsaw, Poland.
Olga
O
Staszewska-Krajewska
Institute of Organic Chemistry of Polish Academy of Sciences, Warsaw, Poland.
Marek
M
Chmielewski
Institute of Organic Chemistry of Polish Academy of Sciences, Warsaw, Poland.
Bartłomiej
B
Furman
D001384:Azetidines / Q000737:chemistry; D003855:Deoxyribose / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry; D015394:Molecular Structure; D009589:Nitrogen Oxides / Q000737:chemistry; D010084:Oxidation-Reduction; D013845:Thienamycins / Q000138:chemical synthesis*
C116379:2-azetidinone; D001384:Azetidines; D009589:Nitrogen Oxides; D013845:Thienamycins; C015388:nitrones; D019344:Lactic Acid; D003855:Deoxyribose; C015537:thienamycin