Fmoc, amino acid protection with

As an example, liquefied mixtures are easily formed by using some amino acids protected with acetyl, Boc-, Fmoc- and Z-groups. Some authors have called the resulting systems eutectic mixtures , but this term should be reserved for the textbook definition as the composition of minimum melting point that freezes isothermally at the eutectic temperature. Hence we refer to them as eutectic melts . 

The 3 -aminoacylated dinucleotides 66 have been prepared by reaction of N-FMOC amino acid fluorides with the p-cyanoethyl-protected dinucleotide. Deprotection with oximate removes all protecting groups without disturbing the aminoacyl linkage. ... 

Amino acid protected with Fmoc and FImb Peptoid methodology... 

FIGURE 5.22 (A) Reaction of an Fmoc-amino acid with 2-chlorotrityl chloride resin.56 The ester bond formed is cleavable by the mild acid, which does not affect tert-butyl-based protectors. (B) Generation of a protected peptide containing cystine by detachment of a chain, deprotection of cysteine residues, and oxidation of the sulfhydryls by the reagent containing iodine. The cations produced are trapped by CF3CH2OH. 

FIGURE 7.14 Activated esters for temporary protection and activation of Fmoc-amino acids for the synthesis of glycopeptides. (A) Reaction of a-D-glucopyranosyl bromide with esterified Fmoc-serine. (B) Reaction of 2-acetamido-2-deoxy-3,4,6-triacetyl- 3-D-glucopyranosyl amine with esterified Fmoc-aspartyl chloride.37-38 Pfp = pentafluorophenyl. 

Although the simplest route to prepare hydroxamic acid derivatives remains the reaction of hydroxylamine with acid chlorides, this last method cannot be apphed to all Af-protected-a-amino acids. The synthesis of Fmoc-protected amino acid hydroxamates represents the only exception to this rule . In fact, Fmoc-amino acid hydroxamates 98 can be synthesized by the acylation of hydroxylamine using Fmoc-amino acid chlorides 97 in the presence of MgO (Scheme 52). The route is simple, efficient, and affords good yields of products. 

Amino acid 1 with n-amino group protected by Fmoc group... 

Marti et alJ4"1 have used a similar approach involving Fmoc-protection. However, they have demonstrated that it is possible to use Fmoc-protected diazo ketones derived from a-amino acids together with a peptide on a solid support with a free N-terminus in a silver-promoted Amdt-Eistert procedure. Hence, homologation and peptide coupling are achieved in one step. This approach has led to the synthesis of a-peptides containing one (l3-amino acid (Scheme 19) and also, if the homologation procedure is used repetitively, to p3-peptides. 

Nitro- or 2,4-dinitrobenzenesulfonamides of primary or secondary amines can be hydrolyzed under mildly basic conditions, and are increasingly being used for amine protection (see Section 10.1.10.7 [123,139,140]). /V-(2-Nitrobenzenesulfonyl)amino acids can be used as an alternative to TV-Fmoc amino acids for the solid-phase synthesis of peptides [141]. Deprotection is achieved by treatment of the polystyrene-bound sulfonamide with a solution of PhSH (0.5 mol/L) and K2C03 (2 mol/L) in DMF for 10 min at room temperature [141], conditions that do not lead to cleavage of esters (e.g. of the Wang linker) or to racemization. The condensation of polystyrene-bound sulfinamides H2N-SO-Pol with aldehydes yields /V-sulfinylimines, which add... 

Standard solid-phase peptide synthesis requires the first (C-terminal) amino acid to be esterified with a polymeric alcohol. Partial racemization can occur during the esterification of N-protected amino acids with Wang resin or hydroxymethyl polystyrene [200,201]. /V-Fmoc amino acids are particularly problematic because the bases required to catalyze the acylation of alcohols can also lead to deprotection. A comparative study of various esterification methods for the attachment of Fmoc amino acids to Wang resin [202] showed that the highest loadings with minimal racemization can be achieved under Mitsunobu conditions or by activation with 2,6-dichloroben-zoyl chloride (Experimental Procedure 13.5). iV-Fmoc amino acid fluorides in the presence of DMAP also proved suitable for the racemization-free esterification of Wang resin (Entry 1, Table 13.13). The most extensive racemization was observed when DMF or THF was used as solvent, whereas little or no racemization occurred in toluene or DCM [203]. 

---