Esters 3-alanine Dmab ester

Microreaction technology has also been applied to peptide synthesis. Haswell and coworkers demonstrated that, using a borosihcate glass microreactor, the desired dipeptide was obtained by the reaction of N-Fmoc-(3-alanine with P-alanine Dmab ester in the presence of DCC (1,3-dicydohexykarbodiimide) (Scheme 5.30) [41,42]. It also was demonstrated that the Fmoc group could be removed by DBU... 

Watts et al. demonstrated multi-step solution-phase synthesis of peptides in a glass microreactor with quantitative yield in 20 min [94]. This should be compared with batch reactions where only moderate yields (40-50%) were obtained in 24 h. Common protecting groups were used, viz. Fmoc was selected for N-protection and Dmab ester for protection of the carboxylic add. The reaction was carried out in the microreactor under electroosmotic flow. Deprotection, which is required to extend the peptide chains beyond dipeptides, was also demonstrated with quantitative yield in the microreactor. In this first microreactor demonstration, only alanine-based peptides were synthesized in later work other amino acids were also used ]95, 96]. 

Fmoc-y9-alanine was pre-activated by introducing the pentafluorophenyi function as an ester group [88]. Dmab-y0-alanine and the pentafluorophenyi ester of Fmoc-/ -alanine reacted and the synthesis of the corresponding y0-dipeptide was realized. 

P 14] For the reaction of the pentafluorophenyl ester of Fmoc-y9-alanine with Dmab-y0-alanine, a similar protocol to that for [P 13] was used [5, 88]. 

OS 16] ]R 5] ]P 13] Using continuous flow in an electroosmotic-driven micro reactor gave a quantitative yield of the dipeptide in only 20 min (600 V for Dmab-/ -alanine 700 V for the Fmoc ester) [5, 88]. Batch synthesis under the same conditions gave only a 40-50% yield [5] (46% in [5]), needing 24 h. 

A reduction in reaction time by virtue of the improved transport properties in eledroosmotic-driven microreadors was demonstrated for the P-dipeptide synthesis using pentafluorophenyl O-activation. Fmoc-P-alanine was preactivated by introducing the pentafluorophenyl fundion as ester group [9]. Dmab-P-alanine and the pentafluorophenyl ester of Fmoc-P-alanine readed, and the synthesis of the corres-... 

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