Triethylamine Tripeptide

A protected serine hydrazide was condensed by the azide method to an S-protected tripeptide H-Asn-Cys-Tyr-NHNH-Cbz to form a protected tetrapeptide Boc-Ser-Asn-Cys-Tyr-NHNH-Cbz 1.02 g of N-rerr-butoxycarbonylserine hydrazide (Boc-Ser-NH-NHj) >n DMF containing HCI in dioxane was mixed at -20 °C with reri-butyl nitrite. This mixture containing the azide Boc-Ser-Nj was neutralized with triethylamine, and a solution of 3.4 g asparaginyl-S-(ethylcarbamoyl)cysteinyl-tyrosinyl 2-(benzyloxy-carbonyl)hydrazide trifluoroacetate was added. After 72 hours at 4 °C a simple work-up procedure and precipitation from methanol-petroleum ether yielded 3 g of impure protected retrapeptide hydrazide. It... 

Peptides. This isocyanide is preferable to simple aliphatic isocyanides (9, 82) for coupling of amino acid derivatives to peptides. Addition of hydroxysuccinimide (9,246) or 1 -hydroxybenzotriazole (6,288) suppresses racemization. It is important to allow the acid component and the additive to react with the isocyanide for a suitable period before addition of the amine component and triethylamine or DMAP. Coupling to di- and tripeptides in yields of 55-72% have been reported. The byproduct, (N-morpholinoethyl)formamide, is removed by an acid wash. 

The mechanism of penicillin biosynthesis from the Arnstein tripeptide, 8-(L-a-aminoadipoyl)-L-cysteinyl-D-valine (ACV), has been extensively studied and reviewed by many chemists. Most of the biosynthetic mechanisms have been ascertained by Baldwin and Bradley using an excellent enzymatic technique.55 However, the first step in the biosynthesis of penicillin, conversion of the Arnstein tripeptide to a cis-P-lactam intermediate, is still a fascinating mechanistic problem. Although Baldwin et al. recently proposed a mechanism involving an iron-bound thioaldehyde formation route via a Pummerer-type cyclization, the intermediate for this mechanism has not been identified. The mechanism of selective formation of the cw-P-lactam ring is still also unknown (Fig. 39).56 These types of biomimetic reactions have been chemically studied. An example of an unsuccessful intramolecular Pummerer cyclization of the sulfoxide involving a cysteine moiety under standard Pummerer conditions was reported by Wolfe et al.57 Although Kaneko reported the conversion of the very simple 3-phenylsulfinyl propionamide into a P-lactam with TMSOTf/triethylamine,58 a successful biomimetic synthesis of... 

The synthesis of ketomethylene pseudopeptide analogues was accomplished by L. Cheng et al., and their biological activity as thrombin inhibitors was tested. These analogues were prepared through a modified Dakin-West reaction under mild conditions and in almost quantitative yield. The required anhydride was prepared from monomethyl succinate, and a large excess of it was mixed with the tripeptide substrate in pyridine in addition to triethylamine and catalytic amounts of DMAP. The reaction mixture was heated for one hour at 40-50 °C. 

The synthesis of a 400 member library of aryl substituted 2-iminohydantoin tripeptide compounds has been accomplished by subjecting resin bound thioureas (36) with 10 equivalents of 1 in the presence of excess triethylamine in DMF for 18 hours.16... 

The formation of a peptide bond using tertiary phosphines and a halogenomethane has been studied in more detail. Trisamino-phosphines and carbon tetrachloride are the reagents of choice. Tripeptides are formed in high yield and with high optical purity. The simultaneous action of triphenylphosphine and carbon tetrachloride on the sulphonyl compounds (41), followed by triethylamine, gave iminophosphoranes (42). 

DPPA (PhO PON l as the peptide coupling agent. Thus, cyclodimerisation of the deblocked tripeptide (240), derived from (239), in the presence of DPPA and triethylamine first leads to (241) in 33% yield. Treatment of (241) with iodine in methanol next effected disulphide bridge formation to (242) which by treatment with thionyl chloride gave the natural product. In an alternative sequence to (243), the tripeptide (239) was first converted to the hexapeptide disulphide (244), using iodine in methanol, which after deprotection to (245) and double cyclisation of the latter with DPPA also gave rise to (242). 

Usual attachment of the first amino acid unit to the chloromethylated poly-styrene-divinylbenzene resin has been improved, for example, with Boc-Asn, by-condensing the amino acid (2.0 mmoles) in DMF with triethylamine (1.8 mmoles) during one day at room temperature. Cleavage of the peptide end product from the polymer as the amide derivative has been accomplished using ammonia in DMF in a sealed reaction vessel at room temperature for 5 days. A careful stud - of several peptide bond-forming reagents and polymer supports in respect to racemization has revealed the DCCI procedure to be far inferior to DCCI-NHS or EEDQ. With the model tripeptide Gly-Ala-Leu (racemization assessment by means of the Izumiya procedure), the product was found to... 

Tripeptides. A soln. of N-carbobenzoxyglycine and triethylamine in tetrahydro-furan cooled to —5°, ethyl chloroformate in tetrahydrofuran added dropwise with stirring, which is continued for 30 min., a soln. of N-trimethylsilyl- -alanine trimethylsilyl ester in tetrahydrofuran added, stirred 90 min. at 5°, 90 min. at room temp., refluxed briefly, cooled, and the above procedure repeated with N-trimethylsilylglycine trimethylsilyl ester, finally treated with aq. NaHCOj N carbobenzoxyglycyl-y9-alanylglycine. Y 76%. F. e. and method s. L. Birkofer, A. Ritter, and P. Neuhausen, A. 659, 190 (1962). 

Isobutyl chloroformate added at —5° to a soln. of benzyloxycarbonyl-L-proline and triethylamine in dry chloroform, stirred 0.5 hr., L-leucine p-nitrophenyl ester hydrobromide added followed by gradual addition of a soln. of triethylamine in chloroform over a period of 15 min., kept 3 hrs. at 0-10° and 1 hr. at room temp., then glycine ethyl ester hydrochloride and triethylamine added with stirring, and kept 2 days at room temp. -> benzyloxycarbonyl-L-prolyl-L-leucylglycine ethyl ester. Y 84%.—The difunctionality of aminoacid active esters and the different reaction rates at the amino and ester ends allow the direct synthesis of tripeptides by two consecutive reactions. F. e., also isolation of intermediates, s. M. Goodman and K. G. Stueben, Am. Soc. 81, 3980 (1959). Peptide synthesis... 

In a 100 ml flask add in the following order 25 ml of DMF, 125 /tl of triethylamine, 0.3 g of amino-tripeptide hydrochloride and 5 g of epoxy-Separon (maximum activation). Sonicate the suspension for 5 min under reduced pressure and incubate at 25 °C for 48 h with shaking. 

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