9-fluorenylmethoxycarbonyl phase

Albericio F, Kneib-Cordonier N, Biancalana S, Gera L, Masada RI, Hudson D, Barany G. Preparation and application of the 5-(4-(9-fluorenylmethoxycarbonyl)aminomethyl-3, 5-dimethoxyphenoxy)-valeric acid (PAL) handle for the solid-phase synthesis of C-terminal peptide amides under mild conditions. J Org Chem 1990 55 3730-3743. 

Urge, L., Kollat, E., Hollosi, M., Laczko, I., Wroblewski, K., Thurin, J., and Otvos Jr., L. (1991) Solid-phase synthesis of glycopeptides synthesis of Na-fluorenylmethoxycarbonyl L-asparagine Nb-glyco-sides. Tetrahedron Lett. 32, 3445-3448. 

C.G. Fields, G.B. Fields, Minimization of tryptophan alkylation following 9-fluorenylmethoxycarbonyl solid-phase peptide synthesis, Tetrahedron Letters 34(1993)6661-6664. 

E Atherton, M Caviezel, H Fox, D Harkiss, H Over, RC Sheppard. Peptide synthesis. Part 3. Comparative solid-phase synthesis of human P-endorphin on polyamide supports using t-butoxycarbonyl and fluorenylmethoxycarbonyl. 

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. 

JD Wade, J Bedford, RC Sheppard, GW Tregear. DBU as an V -deprotecting reagent for the fluorenylmethoxycarbonyl group in continuous flow solid-phase peptide synthesis. Pept Res 4, 194, 1991. 

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

R Sheppard. The fluorenylmethoxycarbonyl group in solid phase synthesis. J Pept Sci 9, 545-552, 2003. 

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... 

The 9-fluorenylmethoxycarbonyl group, developed by Carpino and co-workers in 1972 [257], has become one of the most widely used protective groups for aliphatic or aromatic amines in solid-phase synthesis. For solid-phase peptide synthesis in particular, this protective group plays an important role [258] (Section 16.1). The Fmoc group is not well suited for liquid-phase synthesis because non-volatile side products are formed during deprotection. 

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... 

In this chapter we will summarize chemical methods for the stereoselective attachment of carbohydrates to amino acids, with particular emphasis on the preparation of building blocks for use in solid-phase glycopeptide synthesis based on the 9-fluorenylmethoxycarbonyl (Fmoc) protective group strategy. 

SCHEME 8.1 Solid-phase synthesis of an N-glycan. Cbz, benzyloxycarbonyl, DDQ, 2,3-dichloro-5,6-dicyano-l,4-benzoquinone Fmoc, 9-fluorenylmethoxycarbonyl. 

The 9-fluorenylmethoxycarbonyl group is another distinguished contribution from the Carpino laboratory198199 to the solution-phase synthesis of peptides and latterly it has been adapted to solid-phase peptide synthesis too.200 The Fmoc group is exceptionally stable towards acid thus, carboxylic acids can be converted to acid chlorides with thionyl chloride201 or terf-butyl esters using sulfuric acid and isobutene.202 Furthermore, Fmoc groups are unscathed by HBr in... 

A reactor containing 2-amino-1,3-propanediol (10.0 mmol) and 25 ml of IM NaOH was cooled to 0.2°C and treated with A-(9-fluorenylmethoxycarbonyl)chloride (13.1 mmol) dissolved in 10 ml of CH2CI2 over a 1 hour period. The solution was stirred for 1 hour at 0°C and 4 hours at ambient temperamre. The organic solvent was evaporated and the aqueous residue poured into 70 ml of EtOAc. The organic phase was isolated, washed with 5% aqueous HCl, dilute NaHC03, brine, and dried. The mixture was concentrated, the residue re-crystalhzed in chloroform, and the product was isolated. 

Substrate, /V"-fluorenylmethoxycarbonyl-EEY(P)AA, and the dephosphor-ylated product were separated on a Ci8 Novapak HPLC column (3 mm x 100 mm) using a mobile phase containing 36% acetonitrile-water-0.1% TFA. The eluate was monitored spectrophotometrically at 265 nm, or fluorimetric-ally (excitation, 268 nm emission, 307 nm). 

Alsina, J., Yokum, T. S., Albericio, F., and Barany, G. (1999) Backbone amide linker (BAL) strategy for iV -9-fluorenylmethoxycarbonyl (Fmoc) solid-phase syn-... 

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