14C-labeled and large-scale synthesis of the angiotensin-(1-7)-receptor agonist AVE 0991 by cross-coupling reactions.
The synthesis of (14)C-labeled AVE 0991 ((14)()C-1a) and large-scale synthesis of AVE 0991 (1a) are described. In the key step of the synthesis, the C-C coupling reaction of the imidazole (2) and thiophene (3) building blocks was studied under Suzuki and Stille reaction conditions, respectively. Suzuki reaction gave only moderate yields, whereas the best results were obtained under Stille reaction conditions with up to 64% yield.
Derdau
Volker
V
Chemical Development, Aventis Pharma Deutschland GmbH, 65926 Frankfurt am Main, Germany. volker.derdau@aventis.com
Oekonomopulos
Raymond
R
Schubert
Gerrit
G
D000803:Angiotensin I / Q000378:metabolism; D002250:Carbon Radioisotopes; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D007093:Imidazoles / Q000032:analysis / Q000138:chemical synthesis* / Q000737:chemistry; D007553:Isotope Labeling / Q000379:methods; D015394:Molecular Structure; D010446:Peptide Fragments / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000819:agonists*; D013876:Thiophenes / Q000138:chemical synthesis
C469726:AVE 0991; D002250:Carbon Radioisotopes; D007093:Imidazoles; D010446:Peptide Fragments; D011945:Receptors, Angiotensin; D013876:Thiophenes; D000803:Angiotensin I; C118790:angiotensin I (1-7)