Fmoc

Derivatization is useful for detection of compounds such as amino acids and amines that lack easily detectable groups. For similar reasons, saccharides, as a class of compound, ehcit much interest. Two derivatization schemes have been reported using benzamide (61) and FMOC—hydrazine (62) to produce fluorescent products. 

The carboxamidomethyl ester was prepared for use in peptide synthesis. It is formed from the cesium salt of an A-protected amino acid and a-chloroacetamide (60-85% yield). It is cleaved with 0.5 M NaOH or NaHCOa in DMF/H2O. It is stable to the conditions required to remove BOC, Cbz, Fmoc, and r-butyl esters. It cannot be selectively cleaved in the presence of a benzyl ester of aspartic acid. ... 

Mel, CH3CN morpholine or diethylamine, methanol, 76-95% yield. These conditions also cleave tlie 4 -pyridyl derivative. The Pet ester is stable to the acidic conditions required to remove the BOC and r-butyl ester groups, to the basic conditions required to remove the Fmoc and Fm groups, and to hydrogenolysis. It is not recommended for use in peptides that contain methionine or histidine since these are susceptible to alkylation with methyl iodide. 

Some advantages of the Fmoc protective group are that it has excellent acid stability thus BOC and benzyl-based groups can be removed in its presence. It is readily cleaved, nonhydrolytically, by simple amines, and the protected amine is liberated as its free base. The Fmoc group is generally considered to be stable to hydrogenation conditions, but it has been shown that under some circumstances it can be cleaved with H2/Pd-C, AcOH, MeOH, (t /2 = 3-33 h). ... 

Fmoc-Cl, NaHC03, aq. dioxane, 88-98% yield. Diisopropylethylamine is reported to suppress dipeptide formation during Fmoc introduction with Fmoc-Cl. ... 

Fmoc-OSu (Su = succinimidyl), H2O, CH3CN. The advantage of Fmoc-OSu is that little or no oligopeptides are formed when amino acid derivatives are prepared. 

The Fmoc group is cleaved under mild conditions with an amine base to afford the free amine and dibenzofulvene. The approximate half-lives for the. deprotection of Fmoc-ValOH by a variety of amine bases in DMF are as follows ... 

The half-lives shown in the table ". ill vary depending on the structure of the Fmoc-amine derivative. 

Piperazine attached to a polymer has also been used to cleave the Fmoc group. 

Because of the electron-withdrawing sulfonic acid substituent, cleavage occurs under milder conditions than needed for the Fmoc group (0.1 N NH4OH 1% Na2C03, 45 min). ... 

This method is suitable for the preparation of BOC, Fmoc, Adoc, and Bpoc protected amino acids. The acid chloride is a stable, storable solid. ... 

This is a very important and well tested method for the quantitative determination of loading of Fmoc protected compounds particularly that of Fmoc (fluorenylmethoxycarbonyl) amino acids on solid support. Fmoc groups can... 

Thermitase, pH 7.5, 55°, 50% DMSO, 3-140 min. This method was used to avoid the degradation of base-sensitive side chains during peptide synthesis. The method is compatible with the Fmoc group. ... 

HCl, AcOH, CH2CI2, 5°, 2 h. A t-butyl ether and an Fmoc group were not affected. ... 

This tertiary ester was developed to reduce aspartimide and piperidide formation during the Fmoc-based peptide synthesis by increasing the steric bulk around the carboxyl carbon. A twofold improvement was achieved over the the standard Fbutyl ester. The Mpe ester is prepared from the acid chloride and the alcohol and can be cleaved under conditions similar to those used for the r-butyl ester. ... 

Cleavage is effected with acid. The following table compares the acidolysis rates with Bn and cyclohexyl esters in TFA/phenol at 43°. The Dmp group reduces aspartimide formation during Fmoc-based peptide synthesis. 

This active ester was used for carboxyl protection of Fmoc-serine and Fmoc-threonine during glycosylation. The esters are then used as active esters in peptide synthesis. 

The Dmab group was developed for glutamic acid protection during Fmoc/r-Bu based peptide synthesis. The group shows excellent acid stability and stability toward 20% piperidine in DMF. It is formed from the alcohol using the DCC protocol for ester formation and is cleaved with 2% hydrazine in DMF at rt. ... 

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