Esters pentafluorophenyl ester derivatives

Identification of active library components is done by micro sequencing (peptide libraries) or by incorporation and recognition of the tag associated with each bead (nonpeptide libraries). An example of this latter approach, known as encoded combinatorial synthesis [19], may use the dialkylamine tagging system shown in Fig. 7. The amine group of the tag addition site is acylated with iminodi-acetic anhydride to yield a pentafluorophenyl ester derivative. The active ester is reacted with a binary mixture of secondary alkylamines, leading to a tag polymer. 

Compounds other than nucleic acids can also serve as templates for polymerization to an extent. Tjivikua et al. [33] showed that an adenosine derivative will couple with a pentafluorophenyl ester derivative to form an amide bond. The product is self-complementary hydrogen bonds form between two products in a manner analogous to Watson-Crick base pairing, though the products are not nucleotides. The formation of one product enhances the formation of future products therefore the system is autocatalytic, and may be a model for self-repUcating systems using alternate chemistry (Fig. 9.7). 

The Se-(4-methoxybenzyl)selenocysteine is obtained by reduction of selenocystine with NaBH4 and in situ reaction with 4-methoxybenzyl chloride. 7 The optimized procedure of Tanaka and Soda 32 is preferentially used for the synthesis of the starting selenocystine, which involves reaction of (1-chloroalanine with a 2.3-fold excess of disodium diselenide in aqueous solution at pH 9. Alternatively, the significantly less selenium demanding synthesis of Stocking et al. 33 is used for the preparation of expensive 77Se-selenocystine, this consists of the reaction of methyl (2R)-2-[(/ert-butoxycarbonyl)amino]-3-iodopropanoate with equivalent amounts of dilithium diselenide. Subsequent conversion of SeC(Mob) into the M -Fmoc derivative 7 and finally into the pentafluorophenyl ester 10 is performed following standard procedures. 

Due to the low reactivity of the nitrogen, incorporation of the pyroglutamic acid into endo-positions by stepwise chain elongation is difficult (see reft49 and refs cited therein). It may be achieved using suitably protected aminoacyl-pyroglutamic acid derivatives as dipeptide synthons. These are accessible in satisfactory yields, e.g. by acylation of pGlu-OBzl with N-protected amino acid pentafluorophenyl esters in the presence of NaH or LiHMDS. 49 ... 

The reagents sketched in Figure 13.2 are stable and can be prepared either in solution or on insoluble supports. Activated Boc- or Fmoc-protected amino acid derivatives that are sufficiently stable to be isolated, some of which are commercially available, include acyl chlorides [9,13], fluorides [10,14,15], symmetric anhydrides [16], pentafluorophenyl esters, Af-hydroxysuccinimidyl esters, and 4-nitrophenyl esters [17,18],... 

Nonpreactivated amino acids with protection groups according to the Fmoc-protection strategy (18,19) (EMD Biosciences). Preactivated amino acid derivatives with protection groups according the Fmoc-protection strategy are usually pentafluorophenyl esters (OPfp ester EMD Biosciences or Bachem) (20) (see Note 1). 

One method involves the use of preactivated Fmoc-protected amino acids (e.g., pentafluorophenyl ester). This method has the advantage that only one reagent is necessary since preparation of the amino acid solutions is very simple and the likelihood of mistakes is low. One disadvantage is the higher price of the amino acid derivatives, but due to the small amount of activated amino acids used the absolute difference falls in the range of a few dollars for synthesis of an entire peptide membrane array. Another disadvantage lies in the fact that activated esters are only commercially available for the standard amino acids. 

Scheme 8) are employed for the introduction of nitrogen alkylation into a peptide chain in order to suppress aggregation that interferes with chain assembly. Pentafluorophenyl esters of Fmoc-cysteine derivatives are employed in solid-phase synthesis to circumvent the enantiomerization that occurs during certain onium salt mediated couplings of the corresponding acids which have to be carried out in the presence of tertiary amines. The same phenomenon may apply to serine derivatives. Water-soluble tetrafluoro-4-sulfophenyl esters 22 are available. ... 

Pentafluorophenyl 61 and 4-oxo-3,4-dihydrobenzotriazin-3-yl 65 esters (see Table 16) can be obtained from acid 59 and hydroxy compounds using thionyl chloride the intermediate is the Fmoc amino acid chloride 64 (Scheme 17). In the case of the pentafluorophenyl esters 61, the acid chloride 64 is generated in the absence of the nucleophile and acylation is promoted in the presence of pyridine. While in the case of the 4-oxo-3,4-dihydrobenzotriazin-3-yl esters 65, condensation is achieved by heating the reactants in refluxing dichloromethane. The method is not applicable to derivatives with acid-sensitive side-chain protectors. 

---