Application of hexafluoroacetone as protecting and activating reagent in solid phase peptide and depsipeptide synthesis

Abstract

Hexafluoroacetone-protected/activated hydroxy acids [2,2-bis(trifluoromethyl)-1,3-dioxolan-4-ones] represent recoverable and reusable monomers for the solid phase synthesis of depsipeptides. The reactivities of HFA-protected/activated malic acid and its C α -methylated analog citramalic acid toward resin bound amino acids were studied and are compared herein. The potential of HFA-protected/activated amino acids [2,2-bis(trifluoromethyl)-1,3-oxazolidin-5-ones] such as Phe, Leu, MeLeu, Pro and Tic as pre-activated monomers for solid phase peptide synthesis was also investigated.

Biodegradable Polyesters Derived from Amino Acids

“…In this regard, a promising method for α-polyester formation takes the advantage of bidentate protected/activated hydroxy acid. The notion is that the α-functionality of the hydroxyl acid and carboxylic group of these compounds heterocyclize in one step by reacting with ketone or aldehyde (step d) , or with phosgene to form O -carboxy anhydride OCA (step e) − or alternatively with dichlorodimethylsilane to form a cyclic silyl intermediate (step f). − The later methods are mostly adopted from the peptide synthesis approach and had not yet been fully merged in polymerization processes.…”

A Guideline for the Synthesis of Amino‐Acid‐Functionalized Monomers and Their Polymerizations

“…(Figure 13B,f) or ketones as well as phosgene (Figure 13B,d). [80] The reaction with dichlorodimethylsilane yields a cyclic silyl intermediate (Figure 13B,c), which can then be polymerized. [81] Furthermore, the synthesis of polyesters can be catalyzed by boric acid (Figure 13B,h) or phosphoric acid (Figure 13B,g) to facilitate chain-growth polymerization of an intermediate.…”

Bacteria Hunt Bacteria through an Intriguing Cyclic Peptide

“…Two other important precautions have to be taken into consideration during the synthesis of depsipeptides. First, in the case of head to tail depsipeptides, temporary protection of the hydroxy group is essential, and it has to be orthogonal to the other protecting groups, such as the use of tert ‐butyldimethylsilyl (TBDMS), hexafluoroacetone (HFA), or tetrahydropyranyl ethers (THP) with Fmoc‐SPPS . Second, monitoring completion of the esterification step is critical, and it can be controlled by testing the presence of free hydroxy groups through Pomonis or TCT/AliR tests …”