Fmoc deprotection

The best results were achieved by employing N-(3-dimethylaminopropyl)-N -ethylcar-bodiimide hydrochloride (EDC) as coupling agent. After Fmoc deprotection with piperidine in N,N-dimethylformamide, additional diversity could be introduced by acylation of the liberated amine position. Finally, the acyl cyano phosphoranes could be efficiently cleaved by ozonolysis at -78 °C or by utilizing freshly distilled 3,3-dimethyloxirane at room temperature [65]. The released compounds constituted highly activated electrophiles, which could be further converted in situ with appropriate nucleophiles. 

The desired polymer-bound tryptophan was rapidly generated under microwave irradiation, employing a classical esterification protocol using N,N -dicydohexylcar-bodiimide (DCC) and a catalytic amount of N,N-dimethylaminopyridine (DMAP), followed by subsequent Fmoc deprotection (Scheme 7.68). Cyclocondensations with various carbonyl compounds were performed with catalytic amounts of p-toluene-... 

Sequential acylation reactions were carried out at ambient temperature for 1.5 h using a DMF solution (1.3 mL) of the appropriate A-Fmoc-protected amino acids [Fmoc-Arg/D-Arg(Pmc)-OH, 265 mg Fmoc-Trp/D-Trp(Boc)-OH, 211 mg 0.4 mmol) and then carboxyl activated using TBTU (154 mg, 0.4mmol), HOBt (54mg, 0.4mmol), and DIEA (140pL, 0.8 mmol). Repetitive A"-Fmoc deprotection was achieved using 20% v/v piperidine in DMF (6 min, 2.5 mL min - ). 

Houghten and co-workers[145] introduced a method for combinatorial synthesis of a per-alkylated peptide library using nonspecific N-alkylation. The peptides were synthesized by SMPS methodology 146 in combination with repetitive amide N-alkylation on the solid support after each coupling step. Peptides were synthesized on MBHA-PSty resin using Fmoc chemistry. After Fmoc deprotection the a-amino group was protected by Trt to prevent N -alkylation and to allow only amide alkylation. The on-resin amide alkylation was achieved by amide proton abstraction using LiOtBu in THF followed by nonfunctionalized alkyl and aryl halides in DMSO. 

After the reaction times given in Scheme 38, the respective couplings were quantitative according to chloranil and the Kaiser ninhydrin test and/or HPLC of small cleavage. The peak area of the crude Fmoc-deprotected dodecapeptide was 90% (HPLC k=214nm). The pure cyclic peptide was obtained in an overall yield of 31%. Cyclosporin O was synthesized by a similar procedure.129 ... 

Preparation of the thioacids and their esters via SPPS is mainly restricted to the Boc methodology. The popular Fmoc approach is limited by aminolysis of the thioester bond during removal of the Fmoc group by piperidine. However, a modified Fmoc-deprotecting mixture (1-methyl pyrrolidine/hexamethyleneimine/HOBt/DMSO/NMP 25 2 2 35.5 35.5) gave the final desired peptide ester with 24% yield J24 ... 

The stability of Fmoc amines towards various bases has been investigated in detail [258,261,262]. Ammonia and primary or secondary aliphatic amines in polar aprotic solvents lead to swift deprotection. Further reagents claimed to be useful for Fmoc deprotection are 2% DBU in DMF [263,264], 1% DBU + 1% HOBt in DMF (4 x 2 min no cleavage of thiol esters occurs [265]), KF/NEt3 in DMF [238], 40% Et2NFl... 

Fmoc-deprotection After the reaction is complete, wash the membrane three times with DMF for at least 30 s each. For storage, wash the modified membrane at least twice with methanol or ethanol and dry it in the air stream of a fume hood or using a hair dryer without heat. For resumption of synthesis after storage, treat the membrane once with DMF for 20 min (see Note 5). The Fmoc-deprotection is carried out by treatment of the membrane twice with 20% piperidine in DMF for at least 5 min each. 

Fmoc-deprotection Wash four times with DMF for at least 30 s each. Treat twice with 20% piperidine/DMF for 5 min each. Wash four times with DMF for at least 30 s each. Wash at least twice with methanol or ethanol. 

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