Fmoc protecting group, cleavage

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]. 

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... 

Fmoc chemistry After removal of the N-terminal Fmoc-protective group the synthesized peptide will be deprotected and cleaved from the handle-resin with trifluoroacetic acid (TFA). The peptide will subsequently be separated from scavengers (added during the cleavage), and lyophilized. 

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