With the development of peptide drugs, research and development of various peptides are of growing interest. Currently available methods of peptide synthesis include liquid-phase peptide synthesis and solid-phase peptide synthesis. The methods of solid-phase peptide synthesis are more commonly used. However, many problems will be encountered during the process of liquid-phase syntheses, such as insolubility, hydrophobicity, and time-consuming when dealing with the intermediates.
Recently, scientists have developed a new solid phase synthesis method based on terminal amide modifications. This method has some advantages, like easy to operate, high yields of crude products, and can synthesize some peptides, which can not be synthesized by commonly used solid-phase peptide synthesis methods.
HPLC of crude products liquid-phase peptide synthesis:
HPLC of crude products HPLC data shows that the purity of products obtained by liquid-phase synthesis method is much higher than that by solid-phase synthesis method. Therefore, we will pay more attention to the development of methods of liquid-phase peptide synthesis.
The development of a scalable asymmetric route to a new calcitonin gene-related peptide (CGRP) receptor antagonist is described. The synthesis of the two key fragments was redefined, and the intermediates were accessed through novel chemistry. Chiral lactam 2 was prepared by an enzyme mediated dynamic kinetic transamination which simultaneously set two stereocenters. Enzyme evolution resulted in an optimized transaminase providing the desired configuration in >60:1 /. The final chiral center was set via a crystallization induced diastereomeric transformation. The asymmetric spirocyclization to form the second fragment, chiral spiro acid intermediate 3, was catalyzed by a novel doubly quaternized phase transfer catalyst and provided optically pure material on isolation. With the two fragments in hand, development of their final union by amide bond formation and subsequent direct isolation is described. The described chemistry has been used to deliver over 100 kg of our desired target, ubrogepant.
Liquid phase peptide synthesis - Senn Chem
HPLC data shows that the purity of products obtained by liquid-phase synthesis method is much higher than that by solid-phase synthesis method. Therefore, we will pay more attention to the development of methods of liquid-phase peptide synthesis.