Copper(II) Lysinate and Pseudoproline Assistance in the Convergent Synthesis of the GLP-1 Receptor Agonists Liraglutide and Semaglutide

Standard

Copper(II) Lysinate and Pseudoproline Assistance in the Convergent Synthesis of the GLP-1 Receptor Agonists Liraglutide and Semaglutide. / Guryanov, Ivan ; Orlandin, Andrea; De Paola, Ivan ; Viola, Angelo; Biondi, Barbara; Badocco, Denis; Formaggio, Fernando; Ricci, Antonio; Cabri, Walter.

In: Organic Process Research and Development, Vol. 25, No. 7, 16.07.2021, p. 1598–1611.

Research output: Contribution to journal › Review article › peer-review

Author

Guryanov, Ivan ; Orlandin, Andrea ; De Paola, Ivan ; Viola, Angelo ; Biondi, Barbara ; Badocco, Denis ; Formaggio, Fernando ; Ricci, Antonio ; Cabri, Walter. / Copper(II) Lysinate and Pseudoproline Assistance in the Convergent Synthesis of the GLP-1 Receptor Agonists Liraglutide and Semaglutide. In: Organic Process Research and Development. 2021 ; Vol. 25, No. 7. pp. 1598–1611.

BibTeX

@article{71a8c01c4354414ba697283d64b80713,

title = "Copper(II) Lysinate and Pseudoproline Assistance in the Convergent Synthesis of the GLP-1 Receptor Agonists Liraglutide and Semaglutide",

abstract = "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.",

keywords = "liraglutide, semaglutide, solid-phase synthesis, pseudoproline, GLP-1, copper lysinate",

author = "Ivan Guryanov and Andrea Orlandin and {De Paola}, Ivan and Angelo Viola and Barbara Biondi and Denis Badocco and Fernando Formaggio and Antonio Ricci and Walter Cabri",

year = "2021",

month = jul,

day = "16",

doi = "10.1021/acs.oprd.1c00021",

language = "English",

volume = "25",

pages = "1598–1611",

journal = "Organic Process Research and Development",

issn = "1083-6160",

publisher = "American Chemical Society",

number = "7",

}

RIS

TY - JOUR

T1 - Copper(II) Lysinate and Pseudoproline Assistance in the Convergent Synthesis of the GLP-1 Receptor Agonists Liraglutide and Semaglutide

AU - Guryanov, Ivan

AU - Orlandin, Andrea

AU - De Paola, Ivan

AU - Viola, Angelo

AU - Biondi, Barbara

AU - Badocco, Denis

AU - Formaggio, Fernando

AU - Ricci, Antonio

AU - Cabri, Walter

PY - 2021/7/16

Y1 - 2021/7/16

N2 - 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.

AB - 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.

KW - liraglutide

KW - semaglutide

KW - solid-phase synthesis

KW - pseudoproline

KW - GLP-1

KW - copper lysinate

UR - https://pubs.acs.org/doi/10.1021/acs.oprd.1c00021

UR - http://www.scopus.com/inward/record.url?scp=85111009961&partnerID=8YFLogxK

U2 - 10.1021/acs.oprd.1c00021

DO - 10.1021/acs.oprd.1c00021

M3 - Review article

VL - 25

SP - 1598

EP - 1611

JO - Organic Process Research and Development

JF - Organic Process Research and Development

SN - 1083-6160

IS - 7

ER -

ID: 82306478