Amines fluorenylmethoxycarbonyl

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... 

In the synthesis of analogues of calicheamicin 71 and esperamicin Ajb, Moutel and Prandi employed the glycosyla-tion of a nitrone with a trichloroacetimidate as a key step - /3-N-O glycosidic bond formation. Preparation of the nitrone begins with the alkylation of the known alcohol 69 <1992CC1494> with 1,4-dibromobutane in the presence of sodium hydride. Subsequent aminoalkylation, amine protection with 9-fluorenylmethoxycarbonyl (Fmoc), and reduction with NaBHsCN were followed by nitrone 70 formation with 4-methoxybenzaldehyde (Scheme 8) <2001J(P1)305>. 

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. 

Unfortunately, A-(9-fluorenylmethoxycarbonyl)aziridine-2-carboxylic acid cannot be used in peptide synthesis, since N-deprotection of the respective peptides with secondary amines leads to oxazoline or dehydroamino acid side products. Similarly, N-(tert-butoxy-carbonyl)aziridine-2-carboxylic acid is inappropriate due to the instability of the aziridine moiety to TFA treatment. Attempts to convert A-tritylaziridine-2-carboxylic acid into homogenous and stable active esters as useful intermediates in peptide synthesis leads to positive results only in the case of the pentafluorophenyl ester. 47 Consequently, this active ester seems to be the method of choice for acylating peptides. The related Abhydroxysuc-cinimide and A-3-hydroxy-4-oxo-3,4-dihydro-l,2,3-benzotriazine ester could not be isolated in pure form and have therefore been used as crude products. 47 Access to 2-carbonylazir-idine peptides is also possible by carbodiimide-mediated coupling. Additionally, alkylamides of A-tritylaziridine-2-carboxylic acid are prepared by the azide method,1 5 yet this method fails in peptide coupling steps. 85 ... 

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. 

The Af -acyl groups used in these protection schemes are the formyl and trifluoroacetyl groups. With the advent of alternative alkali-labile amine protecting groups that are cleaved via (3-elimination under milder basic conditions, e.g. 9-fluorenylmethoxycarbonyl (see Section 2.1.1.1.1.3) and substituted sulfonylethyloxycarbonyl groups (see Section 2.1.1.1.1.4), the... 

The and y-carboxyls of Asp and Glu always require protection in classical SPPS or are activated and form a peptide bond with the free amine leading to the formation of a mixture of peptides. An exception to this practice is the use of a C-terminal Asp or Glu attached to the solid support via the side chain, in which case the a-carboxylate is protected. When the desired product is the isoglutamyl or isoaspartyl peptide, protection of the C -carboxyl is required. Benzyl (Bzl) type or t-butyl ( Bu) groups have most commonly been used for the protection of side-chain carboxylates in SPPS based on t-butyloxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc) A-terminal protection, respectively. 

An efficient procedure for debenzylation of esters under solvent-free conditions has been reported by Varma et al. (Scheme 8.7) [42]. By altering the surface characteristics of the solid support cleavage of the 9-fluorenylmethoxycarbonyl (Fmoc) group and related protected amines can be achieved in a similar fashion. The optimum conditions for cleavage of N-protected moieties are use of basic alumina and an irradiation time of 12-13 min at - 130-140 °C. 

In a variation of the Merrifield solid-phase peptide synthesis, the amino group is protected by a fluorenylmethoxycarbonyl (FMOC) group. This protecting group is removed by treatment with a weak base such as the secondary amine piperidine. Write a balanced equation and propose a mechanism for this deprotection. 

The 9-fluorenylmethoxycarbonyl group provides a mode of protection to amines which is stable to acids and catalytic reduction cleavage (Scheme 124) is readily achieved under mild basic, non-hydrolytic conditions, a... 

Godoi et al. (2013) have reported an efficient, quick, and sustainable method for the protection of amines with a 9-fluorenylmethoxycarbonyl (Fmoc) group. It has been fonnd that nnder microwave irradiation this solvent-free approach resulted in good to excellent isolated yields of the desired products within only 5 min. 

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