Fmoc protected amines

These can be converted into amines by direct hydrolysis, or into Fmoc-protected amines by reaction with 9-fluorenylmethanol [224]. 

Most of these procedures are incompatible with common linkers, and are therefore unsuitable for the transformation of support-bound substrates into carboxylic acids. A more versatile approach for this purpose is the saponification of carboxylic esters. Saponifications with KOH or NaOH usually proceed smoothly on hydrophilic supports, such as Tentagel [19] or polyacrylamides, but not on cross-linked polystyrene. Esters linked to hydrophobic supports are more conveniently saponified with LiOH [45] or KOSiMe3 in THF or dioxane (Table 13.11). Alternatively, palladium(O)-mediated saponification of allyl esters [94] can be used to prepare acids on cross-linked polystyrene (Entries 9 and 10, Table 13.11). Fmoc-protected amines are not deprotected under these conditions [160],... 

So, where is the safety catch The important point about Fmoc is that is has a rather acidic proton (p Ca about 25), shown in black. The proton is the Achilles heel treatment of Fmoc-protected amines with base eliminates a fulvene to reveal the NH2 group. 

Alternative Fmoc donors have been proposed for particular purposes for example, [4-(9-fluorenylmethoxycarbonyloxy)phenyl]dimethylsulfonium methylsulfate (20) has been proposed by Okai et al. as a water-soluble reagent for the introduction of the Fmoc group in the presence of aqueous sodium carbonate. O Similarly, a polymer-bound 1,2,3-benzo-triazol-l-ol can be converted by reaction with 9-fluorenylmethyl chloroformate (17) into a polymer-bound 1,2,3-benzotriazol-l-yl 9-fluorenyhnethyl carbonate for the preparation of Fmoc-protected amines in organic and aqueous organic media with all the known advantages of insoluble reagents. ... 

Remove each wash by aspiration leaving dry beads and perform a Kaiser test on the resin (see below). Your test should indicate an Fmoc-protected amine. 

Figure 17 Formation of dibenzofulvene-piperidine adduct by treatment of an Fmoc-protected amine with piperidine.

The AMNB cyclic cMO was synthesized from MOs with the 5 -terminus immobilized on a solid support and the 3 -terminus functionalized with an Fmoc-protected amine. After Fmoc cleavage, the 3 -amine was treated with a disuccinimidyl carbonate-activated AMNB alcohol, followed by two additional steps to install a carboxylic acid function on the linker. Then, the MO was cleaved... 

Figure 3.7 General structures of anticancer chiral ferrocenes functionalized in the cyclopenta-dienyl-derived ligand with (a) a nucleobase (R, =side chain Nb = nucleobase) and (b) an amino acid (R2 = Fmoc-protected amine group) [52,54].

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. 

A more recent publication by Weigand and Pelka has disclosed a polymer-bound Buchwald-Hartwig amination [40], Activated, electron-deficient aryl halides were coupled with conventional PS Rink resin under microwave irradiation. Subsequent acidic cleavage afforded the desired aryl amines in moderate to good yields (Scheme 7.22). Commercially available Fmoc-protected Rink amide resin was suspended in 20% piperidine/N,N-dimethylformamide at room temperature for 30 min to achieve deprotection. After washing and drying, the resin was placed in a silylated microwave vessel and suspended in dimethoxyethane (DME)/tert-butanol... 

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]. 

Immobilization of alcohols 41-42 (e.g. Fmoc protected serine methyl ester, glycosides) and amines (e.g. phenylalamine)... 

Scheme 22 Synthesis of Fmoc-Protected A -(co-AcmS-alkyl)-Gly-OH Building Units by Reductive Amination...

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