9-Fluorenylmethyloxycarbonyl Fmoc group

Glycopeptides are more difficult to synthesize than the conventional peptides, because common protection-deprotection reactions used in the peptide synthesis can cause serious problems to the protective groups used for carbohydrates. Many of these problems have been solved by recent technical innovations [21]. The combination of 9-fluorenylmethyloxycarbonyl (Fmoc) group for N-protection and pentafluo-rophenyl (PFP) group as the activating group for the carboxylic acid allows GlcNAc-Asn... 

In order to design syntheses of complex peptides containing several functional side chains, it is necessary to have a variety of methods of protection and deblocking at disposal. Therefore, it was a major step forward when in addition to reduction and acidolysis deprotection with weak bases, under mild conditions, became a practical possibility. The 9-fluorenylmethyloxycarbonyl (Fmoc) group (Carpino and Han 1970) is removed from the amino group by proton abstraction with secondary amines. A carbamoic add is generated, that, in turn, loses carbon dioxide and affords the free amine ... 

An orthogonal and therefore more reliable combination is offered by the base sensitive 9-fluorenylmethyloxycarbonyl (Fmoc) group ... 

Fig. 3. A mild two-dimensional orthogonal protection scheme for solid-phase synthesis. Temporary -amino protection is provided by the 9-fluorenylmethyloxycarbonyl (Fmoc) group, removed by a base-catalyzed elimination mechanism, typically with piperidine. Permanent tert-bulyl-based side-chain-protecting groups and the p-alkoxybenzyl (PAB) ester handle linkage are both cleaved by treatment with TFA to 5deld the free peptide acid at the end of the synthesis. Details in text.

The details of the solid-phase technique have been improved substantially over the years, but the fundamental idea remains the same. The most commonly used resins at present are either the Wang resin or the PAM (phenyl-acetamidomethyl) resin, and the most commonly used N-protecting group is the fluorenylmethyloxycarbonyl, or Fmoc group, rather than Boc. 

In the case of vancomycin [72], an original study was performed to obtain a well-defined stationary phase structure, since it was reasonably assumed that the antibiotic is randomly linked to the silica by one or both of its amino groups, one belonging to the disaccharide portion (primary), and the other one to the heptapeptide core (secondary). Thus, alternate fluorenylmethyloxycarbonyl (FMOC)-amino-protected derivatives were prepared and immobilized in a packed column, and then vancomycin was recovered by cleavage of the protecting groups. The two defined CSPs obtained, when compared with the CSP produced from native randomly linked vancomycin, showed lower retention and enantioselectivity, also if they still separated the same compounds. Thus, no advantages could be found to choose these phases as an alternative to the native vancomycin CSP. 

Standard amino acid protecting groups that were used routinely in BOC-peptide synthesis. For Lys the -nitrogen has the potential to cyclize. We sometimes protect this with the fluorenylmethyloxycarbonyl (FMOC) protecting group. 

This is the reason why peptide chemists, to decrease the problems of purification prefer for long peptides to use protecting groups (tert-butyloxycarbonyl (t-Boc), benzyloxycarbonyl (Z), fluorenylmethyloxycarbonyl (FMOC).) and classical reagents such as T.B.T.U. (0-lH-benzotriazol-l-yl)-l,l,3,3-tetramethyl uronium tetrafluoroborate), B.O.P.(benzotriazol-l-yl-oxy-tris (dimethylamino) phosphonium hexafluorophosphate and so on in polar solvents such as N,N-dimethylformamide or N-methylpyrrolidone. But this solvents are not compatible with the acidic deprotection reagents such as trifluoroacetic acid and... 

Fluorenylmethyloxycarbonyl (Fmoc)-protected amino acids with appropriate side-chain protecting groups... 

Deprotection of the Mspoc Group. The key deprotection method for this group involves the addition of a nucleophilic reagent to the a,/3-unsaturated sulfone system with the consequent ejection of the carbamate anion. The major advantages of such a process over systems for which deprotection involves a classic /3-elimination process [e.g., the 2-(methylsulfonyl)ethoxycarbonyl (Msc) or 9-fluorenylmethyloxycarbonyl (Fmoc) systems] are... 

In the area of solid-phase peptide synthesis an improved synthesis of 4-(Boc-aminoacyloxymethyl)phenylacetic acids, using the photolabile 4-methoxyphenacyl group has appeared. Fluorenylmethyloxycarbonyl (Fmoc) amino-acid trichlorophenyl esters have been used in solid-phase peptide synthesis in a manner similar to Boc-amino-acid active esters. a-(Phenylacetamido)benzylpolystyrene (PAB-resin) is reported to be a useful new polymeric support for peptide synthesis which has improved acid stability. ... 

The definitive paper on the 9-fluorenylmethyloxycarbonyl group (FMOC) for protection of an amino group has been published. ... 

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