Tryptophane protection

The Doc group, introduced with the chloroformate and either DMAP or /-BuOK, is quite acid stable, but can be cleaved with TFMSA-thioanisole-EDT-TFA (10 min, rt) or with / -cresol-HF (1 h, 0°). The Doc group was found to be suitable for tryptophan protection in /-Bu-based peptide synthesis, since no /-butylation of tryptophan was observed during acid deprotection. 

The Hoc group was developed for tryptophan protection to minimize alkylation during BOC-mediated peptide synthesis. It is introduced with the chloroformate (NaOH, CH2CI2, Bu4N HS04 ) and can be cleaved with HF without the need to include thiols in the cleavage mixture. 

Tryptophan protection. The trytophan nucleus has been protected by acylation with benzyl p-nitrophenyl carbonate to form the CB derivative. The reaction is effected with KF solubilized in 18-crown-6 as base to abstract a proton from the indole ring (equation I). 

Mercaptoethanol was incorporated into the Boc removal solution for tryptophan protection in a Merrifield solid-phase synthesis of hen egg white lysozyme, but the reagent proved unsatisfactory. The problem with the reagent was traced to its polymerization, presumably by HS-3 participation [Eq. (45) and Scheme 2]. 

Selvakannan, R, S. Mandal, S. Phadtare, A. Gole, R. Pasricha, S. D. Adyanthaya, and M. Sastry. 2004. Water-dispersible tryptophan-protected gold nanoparticles prepared by the spontaneous reduction of aqueous chloroaurate ions by the amino acid. J. Colloid Lnterface Sci. 269 (1) 97-102. 

The Dim ester was developed for the protection of the carboxyl function during peptide synthesis. It is prepared by transesterification of amino acid methyl esters with 2-(hydroxymethyl)-l,3-dithiane and Al(/-PrO)3 (reflux, 4 h, 75°, 12 torr, 75% yield). It is removed by oxidation [H2O2, (NH4)2Mo04 pH 8, H2O, 60 min, 83% yield]. Since it must be removed by oxidation it is not compatible with.sulfur-containing amino acids such as cysteine and methionine. Its suitability for other, easily oxidized amino acids (e.g., tyrosine and tryptophan) must also be questioned. It is stable to CF3CO2H and HCl/ether. - ... 

This group was used to protect the tryptophan nitrogen. 

The diphenylphosphinothioyl ester, used to protect a tryptophan, is cleaved with Bu4N F"-3H20/DMF. ... 

Silica gel, heat under vacuum, 80-92% yield. These conditions selectively remove only the indole BOC group from a fully f-Bu-based. protected tryptophan. 

A number of studies have recently been devoted to membrane applications [8, 100-102], Yoshikawa and co-workers developed an imprinting technique by casting membranes from a mixture of a Merrifield resin containing a grafted tetrapeptide and of linear co-polymers of acrylonitrile and styrene in the presence of amino acid derivatives as templates [103], The membranes were cast from a tetrahydrofuran (THF) solution and the template, usually N-protected d- or 1-tryptophan, removed by washing in more polar nonsolvents for the polymer (Fig. 6-17). Membrane applications using free amino acids revealed that only the imprinted membranes showed detectable permeation. Enantioselective electrodialysis with a maximum selectivity factor of ca. 7 could be reached, although this factor depended inversely on the flux rate [7]. Also, the transport mechanism in imprinted membranes is still poorly understood. 

Chen J, Callis PR, King J (2009) Mechanism of the very efficient quenching of tryptophan fluorescence in human gamma D- and gamma S-crystallins the gamma-crystallin fold may have evolved to protect tryptophan residues from ultraviolet photodamage. Biochemistry 48(17) 3708-3716... 

Wu and Sun have presented a versatile procedure for the liquid-phase synthesis of 1,2, ,4-tctrahydro-/i-carbolines [77]. After successful esterification of the MeO-PEG-OH utilized with Fmoc-protected tryptophan, one-pot cyclocondensations with various ketones and aldehydes were performed under microwave irradiation (Scheme 7.68). The desired products were released from the soluble support in good yields and high purity. The interest in this particular scaffold is due to the fact that the l,2,3,4-tetrahydro-/f-carboline pharmacophore is known to be an important structural element in several natural alkaloids, and that the template possesses multiple sites for combinatorial modifications. The microwave-assisted liquid-phase protocol furnished purer products than homogeneous protocols and product isolation/ purification was certainly simplified. 

Y Nishiuchi, H Nishio, T Inui, T Kimura, S Sakakibara. A -Cyclohexyloxycarbonyl group as a new protecting group for tryptophan. Tetrahedron Lett 37, 7529, 1996. 

The indole group of tryptophan is inert to activation and aminolysis reactions, so it does not have to be protected for constructing a peptide. It is sensitive, however, to... 

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