Application of 2‐chlorotrityl resin in solid phase synthesis of (Leu¹⁵)‐gastrin I and unsulfated cholecystokinin octapeptide

Abstract

The carboxyl terminal dipeptide amide, Fmoc-Asp-Phe-NH,, of gastrin and cholecystokinin (CCK) has been attached in high yield through its free side chain carboxyl group to the acid labile 2-chlorotrityl resin. The obtained peptide resin ester has been applied in the solid phase synthesis of partially protected (LeuI5)-gastrin I utilising Fmoc-amino acids. Quantitative cleavage of this peptide from resin, with the t-butyl type side chain protection intact is achieved using mixtures of acetic acid/trifluoroethanol/dichloromethane. Under the same conditions complete detritylation of the tyrosine phenoxy function occurs simultaneously. Thus, the solid-phase synthesis of peptides selectively deprotected at the side chain of tyrosine is rendered possible by the use of 2-chlorotrityl resin and Fmoc-Tyr(Trt)-OH. The efficiency of this approach has been proved by the subsequent high-yield synthesis of three model peptides and the CCKoctapeptide.

The first total synthesis of the cyclodepsipeptide pipecolidepsin A

“…Moreover, taking into account the steric hindrance of the amino acids of the sequence, the most potent HATU/HOAt/DIEA 31 system was adopted as the coupling system for the amide formation. 2-Chlorotrityl resin 32,33 was used as the solid support in the first attempts; however, this support was finally replaced by the more resistant Wang-like resin [3-(4-hydroxymethylphenoxy) propionylaminopolystyrene] 34 , as total cleavage of the peptide during ester formation was detected when scaling up the synthesis using 2-chlorotrityl resin. This resin is cleaved under very mild acid conditions, whereas Wang resin requires stronger acid conditions.…”

Amino Acid-Protecting Groups

“…Thus, they are a better alternative to t Bu for the synthesis of peptides containing residues prone to alkylation such as Trp and Met. 423,441,428 Removal is carried out with 2% TFA in DCM 294 -tert-Butyldimethylsilyl (TBDMS). 424 Unlike the t Bu ethers, the TBDMS ether of Tyr is more acid-labile than the corresponding t Bu ethers; however, it can be removed selectively with TBAF.…”

Synthesis and biological activity of locust AKH‐I and its analogues with modifications at the threonine residues

“…We first synthesized in solid phase the protected N-terminal nonapeptide acid of AKH-I (4) (Scheme 1) using as starting material the Fmoc-Gly-0-Clt-resin ( 2 ) and according to the procedure which has been previously described (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). We first synthesized in solid phase the protected N-terminal nonapeptide acid of AKH-I (4) (Scheme 1) using as starting material the Fmoc-Gly-0-Clt-resin ( 2 ) and according to the procedure which has been previously described (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16).…”