Fluorenylmethoxycarbonyl amino acid

C-D Chang, M Waki, M Ahmad, J Meienhofer, EO Lundell, JD Haug. Preparation and properties of N -9-fluorenylmethoxycarbonyl amino acids bearing tert. -butyl side chain protection. Int J Pept Prot Res 15, 59, 1980. 

P Sieber. An improved method for anchoring of 9-fluorenylmethoxycarbonyl-amino acids to 4-alkoxybenzyl alcohol resins. Tetrahedron Lett 28, 6147, 1987. 

GB Fields, RL Noble. Solid phase synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids. Int J Pept Prot Res 35, 161-214, 1990. 

Peptide Synthesis with iV -9-Fluorenylmethoxycarbonyl Amino Acid... 

Acylation with A"-9-Fluorenylmethoxycarbonyl Amino Acid Fluorides... 

Figure 1 Coupling of A -9-Fluorenylmethoxycarbonyl Amino Acid Fluorides with H-(Me)Aib-OMel l ( Phe, T Ala, Val)P8]...

Lepri et al. investigated the chromatographic behavior of racemic dinitropyridyl, dinitrophenyl, dinitrobenzoyl, 9-fluorenylmethoxycarbonyl amino acids, tryptophanamides, lactic acid derivatives, and unusual enantiomers such as binaphthols on reversed phase TLC plates developed with aqueous-organic mobile phase containing bovine serum albumin (BSA) as chiral agent. More than 75 racemates has been separated in these experiments with planar chromatography using BSA in mobile phase. BSA showed enantioselectivity towards racemates with structures completely different from amino acids, their derivatives, and similar compounds such as hydroxy acids. 

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... 

E Atherton, JL Holder, MMeldal, RC Sheppard, RM Valerio. 3,4-Dihydro-4-oxo-l,2,3-benzotriazin-3-yl esters of fluorenylmethoxycarbonyl amino acids as self-indicating reagents for solid phase peptide synthesis. J Chem Soc Perkin Trans 1 2887, 1988. 

Cameron, L R, Holder, J L, Meldal, M, Sbeppard, R C, Peptide synthesis. Part 13. Feedback control in solid phase synthesis. Use of fluorenylmethoxycarbonyl amino acid 3,4-dihydro-4-oxo-l,2,3-benzotriazin-3-yl esters in a fully automated system, J. Chem. Soc. Perkin Trans. 1, 2895-2901, 1988. 

Lepri, L., Coas, V. and Desideri, GP, Reversed phase planar chromatography of optically active fluorenylmethoxycarbonyl amino acids with bovine serum albumin in the mobile phase, J. Planar Chromatogr, 5 294,1992. 

Krausz el al. have synthesised two series of amino acid porphyrinylsugar derivatives (Fig. 5). One of them involves the coupling of adequate glycoporphyrin derivatives, prepared by pyrrole/aldehyde condensation methodology, with 9-fluorenylmethoxycarbonyl-L-alanine (Fmoc-L-alanine) to give the tri-, di-, and mono-alanine glycoporphyrin derivatives 54—57 after the deprotection step the other series (58) involves a glucosylamino acid moiety instead of the alanine in their preparation.21,44... 

L Lapatsanis, G Milias, K Froussios, M Kolovos. Synthesis of A-2,2,2,-(trichloro-ethoxy carbonyl)-L-amino acids and A-(fluorenylmethoxycarbonyl)-L-amino acids involving succinimidoxy anion as a leaving group in amino acid protection. Synthesis 671, 1983. 

A recently described approach involving zinc dust for eliminating acid allows acylation by 9-fluorenylmethoxycarbonyl chloride without dimer formation. The amino acid is dissolved in acetonitrile with the aid of hydrochloric acid, and zinc dust is added to destroy the acid and deprotonate the zwitter-ion, reducing the protons to gaseous hydrogen (Figure 3.16). Acylation is effected in the presence of zinc dust, which reduces the proton that is liberated by the reaction as soon it is formed. See Section 7.7 for another possible impurity in Fmoc amino acids.34,36-39... 

On the other hand, optionally added co-ions of the eluent may also interfere with the ion-exchange process through competitive ion-pairing equilibria in the mobile phase. The effect of various amines added as co-ions to the polar-organic mobile phase was systematically studied by Xiong et al. [47]. While retention factors of 9-fluorenylmethoxycarbonyl (FMOC)-amino acids were indeed affected by the type of co-ion, enantioselectivities a and resolution values Rs remained nearly constant. For example, retention factors k for FMOC-Met decreased from 17.4 to 9.8 in the order... 

Scheme 14 shows a typical example in a series of reactions in which a supported amino acid reacted with fluorenylmethoxycarbonyl isothiocyanate to give a supported (on Rink s amide)35 thiourea.36 Removal of the protection followed by 5-alkylation gave supported isothioureas. Reaction of these with amines, then cleavage from the resin, afforded substituted guanidines. For 10 examples the purities were between 40 and 92%. An aryl group separates the resin from the guanidine, just as in the sequences shown in Schemes 11 and 12. 

V,7.V,8aS)-3-(AUyloxycarbonylmethyl)-7-[(9-fluorenylmethoxycarbonyl)amino]-l,4-dioxooctahy-dr pyrr lo[l,2-a]pyrazhie-8a-acetic Acid 11421... 

For the 9-fluorenylmethoxycarbonyl (Fmoc) protection of amino acids, Chinchilla et al.36,37 prepared a similar ROMP-polymer that supports an activated. V-hydroxysuccinimide Fmoc-carbonate (Table VII, entry 31). Various Fmoc-amino acids are prepared in pure form after removal of the polymer reagent by filtration and aqueous phase separation. 

Wang and Porter [92] resolved the enantiomers of oxazepam, lorazepam, and temazepam using /1-cyclodextrin as the CMPA by CEC. The authors varied separation parameters such as voltage and mobile phase. Wei et al. [93] resolved the enantiomers of phenylephrine and synephrine by varying the concentration of /1-cyclodextrin (CMPA), pH, electrolyte concentration, and temperature. Lelievre et al. [99] separated the enantiomers of chlorthalidone using hydroxypropyl /1-cyclodextrin as the CMPA. Lammerhofer and Lindner [90] resolved the enantiomers of N-derivatized amino acids (e.g., 3,5-dinitrobenzoyl, 3,5-dinitro-benzyloxycarbonyl, 2,4-dinitrophenyl, and 9-fluorenylmethoxycarbonyl amino... 

---