Synthesis of small tripeptide molecules through a catalysis sequence comprising metathesis and aminohydroxylation.
Tripeptidic structures were synthesized by using a combination of two independent consecutive catalytic procedures. Cross-metathesis of N-acroyl amino acid esters yields fumaric amide compounds with exclusive E double-bond geometry. This represents an unprecedented example of complete double-bond selectivity in this kind of reaction. A subsequent asymmetric aminohydroxylation of the chiral fumaric amides was carried out without the need of any further ligand and gave high yields and no side products. This reaction transforms the central fumaric amide unit into a hydroxy aspartic acid moiety and relies on the inherent stereochemistry of the starting fumaric diamides. An additional feature of our sequence is the ease of generating stereochemical diversification within the aminohydroxylation reaction. As a consequence, rapid conformational and configurational diversification can be achieved from the overall two-step catalytic sequence. The versatility of this approach is demonstrated by starting from two different N-acroyl amino esters, which led to the synthesis of eight structurally and stereochemically different tripeptides that could all be identified individually. As such, the present two-step catalytic approach should serve to efficiently synthesize large families of tripeptidic molecular probes.
Streuff
Jan
J
Kekulé-Institut für Organische Chemie und Biochemie, Rheinische Friedrich-Wilhelms-Universität, Gerhard-Domagk-Strasse 1, 53121 Bonn, Germany.
Nieger
Martin
M
Muñiz
Kilian
K
D000577:Amides / Q000737:chemistry; D000588:Amines / Q000737:chemistry*; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D002384:Catalysis; D005650:Fumarates / Q000737:chemistry; D006900:Hydroxylation; D009842:Oligopeptides / Q000138:chemical synthesis*
D000577:Amides; D000588:Amines; D000596:Amino Acids; D005650:Fumarates; D009842:Oligopeptides; C032005:fumaric acid