SIMPLE SYNTHESIS OF CIS-4-HYDROXY-L-PROLINE AND DERIVATIVES SUITABLE FOR USE AS INTERMEDIATES IN PEPTIDE-SYNTHESIS

An intramolecular Mitsunobu reaction in the presence of triphenylphosphine-diethyl azodicarboxylate (TPP-DEAD) resulted in the conversion of trans-4-hydroxy-N-trityl-L-proline to 5-triphenylmethyl-2-oxa-5-aza-bicyclo[2.2.1]heptan-3-one. This bicyclic lactone proved to be a key intermediate in the sy...

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Published inActa chemica Scandinavica (Copenhagen. 1989) Vol. 44; no. 3; pp. 243 - 251
Main Authors PAPAIOANNOU, D, STAVROPOULOS, G, KARAGIANNIS, K, FRANCIS, GW, BREKKE, T, AKSNES, DW
Format Journal Article
LanguageEnglish
Published FREDERIKSBERG C Wiley 1990
Subjects
Biochemistry & Molecular Biology
Chemistry
Chemistry, Multidisciplinary
Life Sciences & Biomedicine
Physical Sciences
Science & Technology
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Summary:An intramolecular Mitsunobu reaction in the presence of triphenylphosphine-diethyl azodicarboxylate (TPP-DEAD) resulted in the conversion of trans-4-hydroxy-N-trityl-L-proline to 5-triphenylmethyl-2-oxa-5-aza-bicyclo[2.2.1]heptan-3-one. This bicyclic lactone proved to be a key intermediate in the synthesis of cis-4-hydroxy-L-proline and derivatives thereof. TPP-DEAD-catalysed methanolysis of the key lactone gave the methyl ester of cis-4-hydroxy-N-trityl-L-proline, while ammonolysis in isopropyl alcohol provided the corresponding amide. p-Toluene-sulfonic acid treatment of the lactone, ester and amide led to detritylation and formation of the corresponding p-toluenesulfonates. Saponification of the key intermediate provided cis-4-hydroxy-N-trityl-L-proline which was first benzylated and then elaborated to the 1-hydroxybenzotriazolyl ester. This last ester and the three p-toluenesulfonates prepared above were utilised for the incorporation of cis-4-hydroxy-L-proline in the synthesis of model peptides.
ISSN:0904-213X
DOI:10.3891/acta.chem.scand.44-0243