DOI

  • Ivan Guryanov
  • Andrea Orlandin
  • Ivan De Paola
  • Angelo Viola
  • Barbara Biondi
  • Denis Badocco
  • Fernando Formaggio
  • Antonio Ricci
  • Walter Cabri
A growing interest in peptides as active pharmaceutical ingredients (APIs) requires the development of efficient strategies for their preparation. This is particularly challenging in the case of long peptides with a strong tendency for aggregation and folding. Here, we describe the pseudoproline-assisted convergent synthesis of GLP-1 receptor agonist lipopeptides liraglutide and semaglutide, which involves the stepwise condensation of three fragments in the solid phase. The insertion of a pseudoproline residue at the site of fragment coupling prevents aggregation and allows obtaining these peptides with excellent purity and high yield. In addition, for the synthesis of lipidated side chains, we developed a novel approach that involves copper(II) lysinate intermediates and can be particularly suitable for the industrial preparation of both liraglutide and semaglutide and other peptides with a similar branched structure.
Язык оригиналаанглийский
Страницы (с-по)1598–1611
Число страниц14
ЖурналOrganic Process Research and Development
Том25
Номер выпуска7
DOI
СостояниеОпубликовано - 16 июл 2021

    Предметные области Scopus

  • Физическая и теоретическая химия
  • Органическая химия

ID: 82306478