Tirzepatide Intermediates
Tirzepatide is a peptide composed of multiple amino acids that can simultaneously activate two important gut glucagon receptors - glucose dependent insulinotropic peptide receptor (GIPR) and glucagon like peptide-1 receptor (GLP-1R).
Tirzepatide significantly reduces body weight and fat by regulating appetite and reducing food intake. Suitable for obese individuals with BMI ≥ 28 kg/m ², or overweight individuals with BMI ≥ 24 kg/m ² and comorbidities such as hypertension, dyslipidemia, and hyperglycemia.
From the perspective of the synthesis process of peptide API, most fragments are synthesized using chemical synthesis methods, including solid-phase synthesis and liquid-phase synthesis. Therefore, a large amount of protected amino acids are required as raw materials. In order to save efficiency and cost, Tirzepatide can also use protected dipeptides or Tirzepatide intermediates for peptide fragment synthesis. The following table lists the dipeptide or Tirzepatide fragments supplied in bulk in Omizzur's GLP-1 peptide synthesis process:
Name | CAS | Molecular formula |
AEEA-AEEA | 1143516-05-5 | C12H24N2O7 |
AEEA-AEEA-AEEA | 2773558-06-6 | C18H35N3O10 |
OtBu-C20-Glu(AEEA-AEEA-OH)-OtBu | 1188328-37-1 | C45H83N3O13 |
Fmoc-Lys(tBuO-Ara-Glu(AEEA-AEEA)-OtBu)-OH | 2915356-76-0 | C66H105N5O1 |
Fmoc-L-Lys [C20-OtBu-Glu (OtBu)-AEEA-AEEA]-OH | 2460751-66-8 | C66H105N5O16 |
Boc-Tyr(tBu)-Aib-Glu(OtBu)-Gly-OH | 2682040-93-1 | C33H52N4O10 |
Fmoc-Ser(tBu)-Gly-OH | 81672-17-5 | C24H28N2O6 |
Fmoc-Ala-Pro-OH | 186023-44-9 | C23H24N2O5 |
Fmoc-Ile-Aib-OH | 2171139-20-9 | C25H30N2O5 |
Boc-Tyr(tBu)-Aib-OH | 2639221-78-4 | C22H34N2O6 |
C20-γ-Glu(AEEA-AEEA-OSu)-OH | 1188328-38-2 | C41H70N4O15 |
tBuO-C20-γ-Glu(AEEA-AEEA-OSu)-OtBu | 1118767-17-1 | C49H86N4O15 |
C20-Glu-AEEA-AEEA-OSU | N/A | C41H70N4O15 |
C20-OtBu-Glu(OtBu)-AEEA-AEEA-OSU | N/A | N/A |
18-(tert-Butoxy)-18-oxooctadecanoic acid | 843666-40-0 | C22H42O4 |
20-(tert-Butoxy)-20-oxoicosanoic acid | 683239-16-9 | C24H46O4 |
Tirzepatide API Synthesis
The synthesis of Tirzepatide is mainly based on peptide synthesis technology, and in the synthesis process, the raw materials are mainly high-quality amino acids. By introducing protective groups such as Boc, Fmoc, etc., the active groups of amino acids are protected, followed by condensation reactions to form peptide chains. In this process, precise control of reaction conditions and reaction time is required to ensure the correct formation of peptide chains. After the formation of the peptide chain, the protective group is removed, and folding and disulfide bond formation are carried out. Finally, pure Tirzepatide is obtained through purification techniques such as counter current chromatography and high-performance liquid chromatography.
Tirzepatide contains a side chain similar to the structure of semaglutine, which is composed of a C20 fatty acid dimer of glutamic acid and 2- (2- (2-aminoethoxy) ethoxy) acetic acid, connected to the lysine residue of the side chain.
Solid-phase Peptide Synthesis & Tirzepatide
Solid-phase peptide synthesis methods have been developed and are currently mainly divided into two categories: Boc solid-phase synthesis method and Fmoc solid-phase synthesis method.
The dual agonist tirzepatide developed by Eli Lilly is synthesized by solid-phase synthesis of multiple short peptide fragments (AA1-14, AA15-21, AA22-29, and AA30-39 fragments), and then combined with the above four fragments through liquid-phase synthesis to obtain the final product.
In the solid-phase synthesis process of these short peptide fragments of tirzepatide , it is not achieved by coupling amino acids one by one, but by coupling dipeptides or tirzepatide protected by Fmoc or Boc to obtain multiple long fragments. This can reduce the amount of amino acids used, while also reducing the generation of impurities, improving production efficiency and product quality.
About Omizzur
Omizzur is an innovative company based on solid underlying technologies in chemistry and biology, focusing on leading industry quality improvement. Its core business now includes outsourcing services for biopharmaceutical research and development, as well as the research and production of peptide synthesis, amino acid raw materials, and life science reagents.
Omizzur's advantageous products include high-quality long-acting peptide intermediates, protected amino acid raw materials, Linkers, Resin and biological dye reagents, etc.
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