Methods and Approaches for the Solid‐Phase Synthesis of Peptide Alcohols

Abstract

Many methods have been developed for attaching an alcohol functionality to a solid support. However, not all of these methods are used to obtain peptide alcohols. In this Minireview, we will discuss several of the most important methods and approaches for the synthesis of peptide alcohols and the attachment of hydroxy groups to a solid support for the synthesis of cyclic peptides. Some of the methods include the use of functionalized Wang resin and the attachment of an alcohol to an enol ether resin. We also discuss the use of the chlorotrityl resin, one of the most common linkers used to obtain peptide alcohols. In addition, we outline the recently developed resins with the Rink, Ramage and Sieber handles. The majority of these methods have been used to synthesize many important drugs, such as octreotide and the antibiotic peptaibols.

Anticancer and Targeting Activity of Phytopharmaceutical Structural Analogs of a Natural Peptide from Trichoderma longibrachiatum and Related Peptide-Decorated Gold Nanoparticles

“…Cationic [ 48 ], membrane-active peptides should indeed have an advantage in interacting with tumor cells since the latter have a higher concentration of negatively charged glycoproteins and phosphatidylserine in their membrane than healthy cells [ 49 , 50 ]. The newly designed and produced sequences Leu4-NH2 and Api8-NH2 ( Table 1 ) are cheaper versions of the related Leu4-Lol and Api8-Lol peptaibols (endowed with a C-terminal Leucinol instead of the -Leu-NH2) in that the SPPS 2-chlorotrityl resin preloaded with the 1,2-aminoalcohol Lol [ 51 , 52 ] is very expensive compared to the rink amide resin herein used to produce Leu4-NH2 and Api8-NH2. Leu4-NH2 was selected because of the peculiar biological activity of the trichogin analog Leu4-Lol [ 27 ], which was proven to be able to interact with phospholipid membranes while being inactive both towards bacteria and eukaryotic cells [ 27 , 29 ].…”

Recent Progress in Solid‐Phase Total Synthesis of Naturally Occurring Small Peptides

“…[16][17][18][19][20][21][22] Accompanying these developments of solid-phase organic synthesis, some synthetic methodologies primarily utilized in the solution phase successfully transferred onto the solid phase, which is in turn to promote the development of solid-phase peptide synthesis. [23][24][25][26][27] Although some reviews related to the SPPS have mentioned some cases of natural peptides in recent years, they are mainly focused on the topics of the green and sustainable SPPS, [28][29][30] synthesis of one specified category of peptides, [31] or talking about certain strategies (Fmoc SPPS, [32] peptide ligation, [33] transition-metal catalysis, [34] etc.). Few of them are specially focused on the naturally occurring small peptide synthesis.…”

“…Although some reviews related to the SPPS have mentioned some cases of natural peptides in recent years, they are mainly focused on the topics of the green and sustainable SPPS, [28–30] synthesis of one specified category of peptides, [31] or talking about certain strategies (Fmoc SPPS, [32] peptide ligation, [33] transition‐metal catalysis, [34] etc.). Few of them are specially focused on the naturally occurring small peptide synthesis [27] .…”