Esters peptide thio

T2 resin synthesis of substituted amines, amides(peptides), (thio)urcas, hydrazines, alcohols, esters guanidines alkyl halides, sulfoximines. ... 

Use me thio esters (-C02SR ) obtained from me ROCO-Peptide-SR -linker-resins assembled by solid-phase synthesis (see Section 7.10).74... 

Only very few among the common amino acids possess a pK within the range 5.8-7.0. Therefore, the imidazole ring of histidine was suspected very early to represent the group responsible for nucleophilic attack on the substrate (38). The pK of free imidazol is 6.9 (39) that of imidazol, contained in histidine or its peptides, varies between 5.6 and 7.1 (40). Imidazol is well known to form unstable acyl derivatives, which undergo spontaneous hydrolysis because of the presence of the resonating triad unit —-N—C= N— (41). In addition, imidazol and its derivatives catalyze the hydrolysis of certain esters, especially those derived from phenols (42). Likewise, the behavior of imidazol towards thio esters reflects exactly the specificity of ChE s (see IV, 4). Thus, thiol esters are split (43), whereas thiono esters are resistant (21). 

Various comprehensive studies on the polymerization of enantiopure and racemic esters of a-amino acids performed at the air/water interface to yield peptides have been reported over the years [189,190]. Recent reinvestigations of the products of these reactions by MALDI-TOF MS have demonstrated, however, that they are not longer than dipeptides [191]. For this reason, such esters cannot be regarded as realistic prebiotic model systems for the formation of long oligopeptides. On the other hand, amphiphilic Na-carboxyanhydrides [192] and thio-esters [193] of a-amino acids yield longer oligopeptides. 

Fig. 4. Scheme of NCL. The mechanism allows the straightforward preparation of small proteins with native backbone structures from fully unprotected synthetic peptide building blocks. The initial tran -thioesterification step includes the chemo-selective reaction between one peptide with a C-terminal a-thioester group (peptide 1) and second peptide with an N-terminal cysteine residue (peptide 2). Generated thio-ester-linked intermediate spontaneously rearranges to form a native peptide bond at the site of ligation. 

Nonribosomal peptide synthetases (NRPSs) function similarly to the ribosome in a second way They act processively to build a peptide chain. In both cases, the amine group of the incoming aminoacyl monomer attacks the (thio)ester bond that links the nascent peptide to its carrier, which translocates the chain while elongating it by one monomer (22). 

M HCl, dioxane (toxic), 92-100% yield. This method was used to remove BOC groups from peptides in the presence of f-Bu esters, ethers, and thio-ethers, but not phenolic f-Bu ethers. ... 

The first reported solid-phase synthesis of head-to-tail cyclic peptides was based on the intramolecular aminolysis of resin-bound o-nitrophenyl esters. The cyclization proceeds concurrently to cleave the peptide from the resin, after deprotection and neutralization of the AT-terminal residue (Scheme 2A). Accordingly, Fridkin et al. [3] reported the preparation of several simple, unhindered cyclopeptides, such as cyc/o(Ala-Gly-Ala-Ala). Similarly, Flanigan and Marshall [4] obtained activation of the resin-bound peptide ester, after elongation of the peptide chain, by oxidation of the 4-(methyl-thio)phenyl (MTP) linker to a sulfonyl ester. Subsquent deblocking of the A-terminal residue and intramolecular condensation yielded the desired cyclic peptide. However, this method was found not to be suitable for the synthesis of longer and more hindered cyclic peptides [5]. 

Carboxamides are usually converted to sulfonamides as illustrated by the synthesis of the hypoglycemic sulfonyl isostere of glybenclamide. " The isosteric replacements for peptidic bonds have been summarized by Spatola and by Fauchere. The most used and well-established modifications are iV-methylation configuration change (D-configuration at Ca) formation of a retroamide or an a-azapeptide use of aminoisobutyric or dehydroamino acids replacement of the amidic bond by an ester (depsipeptide), ketomethylene, hydroxyethylene or thio-amide functional group carba replacement of the amidic carbonyl and use of an olefinic double bond (Fig. 13.17). 

An initial search for the thioester-forming sequence indicated that a peptide 67 containing a Cys-Pro-Cys/Ser sequence appeared to be converted into the DKP thioester. An N-SIO acyl shift at the second Cys or Ser residue (path b) would produce a Cys-Pro (thio)ester structure 68b. Once the CPE structure is formed, the DKP thioester 52 would be obtained via an N-S acyl shift at the first Cys residue (path a) followed by DKP formation (path c). The order of reactions a and fe would not be critical for the overall reaction. As of this writing, DKP thioester formation from the CPC peptide was demonstrated only in model systems (Scheme 22). When the CPC peptide, H-Ala-Lys-Leu-Arg-Phe-Gly-Cys-Pro-Cys-NH2 (70), was treated at 110°C under acidic conditions, dilute hydrochloric acid or heptafluorobutyric acid (HFBA), the corresponding DKP thioester 71 was obtained. Although epimerization in the DKP moiety was observed, the reaction mixture was reacted with cysteinyl peptide, H-Cys-Tyr-NH2 (72), to produce 73 as a single isomer. 

Peptidyl thioester TQFCFH-SCHjCHjCONH, (synthesized by BocKihemistry on thio-ester resin) and cysteinyl peptide CKVLTTGLPALISW (synthesize by Fmoc-chemistry)... 

Preparation of Isothiocyanates.—A conventional synthetic method is illustrated in the preparation of AT-(isothiocyanato-acyl)-amino-acids, e.g. S C N (CH2) C0 NHCHR C02H, starting from the peptide trimethyl-silyl ester treatment with CSg and an alkyl chloroformate gives an alkoxycarbonyl dithiocarbamate which readily cyclo-eliminates COS and alkanol. Acylation of an amino-acid trimethylsilyl ester with SCN--(CH2) C0 C1 provides an alternative route cyclization of an a-isothio-cyanato-acid (158) to a 2-thio-oxazolidone (159) occurs readily in solution, ... 

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