Fmoc protecting group

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). ... 

An Fmoc protecting group can be removed from an amino acid by treatment with the amine base piperidine. Propose a mechanism. 

The completion of the total synthesis only requires a few deprotection steps. It was gratifying to find that the final deprotections could be conducted smoothly and without compromising the newly introduced and potentially labile trisulfide residue. In particular, exposure of intermediate 101 to the action of HF pyridine results in the cleavage of all five triethylsilyl ethers, providing 102 in 90% yield (Scheme 23). Finally, hydrolytic cleavage of the ethylene ketal with aqueous para-toluenesulfonic acid in THF, followed by removal of the FMOC protecting group with diethylamine furnishes calicheamicin y (1) (see Scheme 24). Synthetic calicheami-cin y, produced in this manner, exhibited physical and spectroscopic properties identical to those of an authentic sample. 

An alternative approach is the cleavage of a UV-active protecting group from the resin, such as the widely used Fmoc Test. The quantitation of the 9-fluorenyl-methyloxycarbonyl (Fmoc) protecting group for amines is used in SPPS as an indirect method to determine the extent of a peptide coupling reaction. Similar approaches have also been recently reported for the quantitation of supported thiols [151, 154] and have also been the subject of an excellent review [148]. 

The procedure described above can now he repeated. First the reaction chamber is washed with a solution containing the third unit to be added (the third amino acid). This amino acid is also protected with either a Boc or Fmoc protective group. When the third unit is added to the existing two-unit structure, a three-unit (tripeptide) product is obtained. The protecting group is then removed and a fourth group added to permit the process to continue. The process can then be repeated as often as desired. 

As in the case of dipeptide esters in solution, the rate of piperazine-2,5-dione formation in SPPS strongly depends on steric and chiral features of the original dipeptide structure.11501 The rate of the cyclization increases upon catalysis by weak carboxylic acids.11761 However, it was also reported that piperazine-2,5-diones are formed under basic conditions, e.g. removal of the Fmoc protecting group. Formation of piperazine-2,5-diones is generally overcome by... 

Fmoc-EALAKA-Rink-resin (1.25 equiv) was allowed to swell in DMF (1.5 mL) for 1 h. The DMF was removed by filtration and the resin washed with additional DMF (1.5 mL). The resin was then treated with 20% piperidine/DMF (2 x 1.5 mL) for 10 min to remove the Fmoc protecting group, filtered, and washed with additional DMF (10 x 1.5 mL). A soln of the carboxylic acid prepared above, EDC (1 equiv), and HOBt (1 equiv) in DMF (1.5 mL) was added to the resin and the slurry was stirred for 1 h. The resin was filtered, washed with DMF (2 x 1.5 mL) followed by CH2Q2 (2 x 1.5 mL), and stored in vacuo overnight. 

A special group of base-labile linkers for carboxylic acids rely on cleavage by 3-elimination. Here, the resin-bound alcohol must bear an electron-withdrawing group in the [3 position (Figure 3.8), which facilitates elimination by acidifying this position. Mechanistically, these linkers are closely related to the Fmoc protective group, and... 

This is a very simple and short method for the deprotection of N-Cbz and N-Bn groups, which is also applicable for N-Cbz protected amino acids and is compatible with Fmoc protecting groups, which remain unaffected under these conditions. Furthermore, the microwave protocol is fully compatible with enantiomerically pure amino acids and peptides, as no racemisation was observed in the resulting free amines. 

For removal of the Fmoc protecting group, the peptide T4-(4a14,4COCH2ONHFmoc) (13 mg, 1.56 pmol) was dissolved in 10% piperidine/DMF (200 pL) and stirred at rt for 30 min. After precipitation with cold Et20, the product was isolated by centrifugation (5 min, 4000 rpm), lyophilized from MeCN/H20 and purified by HPLC (gradient 5—95% MeCN) yield 10.3mg (90%). 

An alternative route to the resin-bound peptide 3 is shown in Scheme 4. The peptide was synthesized by solid-phase synthesis except that Boc-Lys(Fmoc)-OH was used instead of Boc-Lys(CHO)-OH to yield 6. The e-amino Fmoc protecting groups were removed to give 7 and the free amino groups formylated with formic anhydride to give 3. 

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