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AJIPHASE®: A Highly Efficient Synthetic Method for One‐Pot Peptide Elongation in the Solution Phase by an Fmoc Strategy
Author(s) -
Takahashi Daisuke,
Inomata Tatsuji,
Fukui Tatsuya
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201702931
Subject(s) - fulvene , chemistry , combinatorial chemistry , protecting group , solubility , peptide , alkyl , solvent , peptide synthesis , precipitation , molecule , extraction (chemistry) , organic chemistry , aqueous solution , stereochemistry , biochemistry , physics , meteorology
We previously reported an efficient peptide synthesis method, AJIPHASE®, that comprises repeated reactions and isolations by precipitation. This method utilizes an anchor molecule with long‐chain alkyl groups as a protecting group for the C‐terminus. To further improve this method, we developed a one‐pot synthesis of a peptide sequence wherein the synthetic intermediates were isolated by solvent extraction instead of precipitation. A branched‐chain anchor molecule was used in the new process, significantly enhancing the solubility of long peptides and the operational efficiency compared with the previous method, which employed precipitation for isolation and a straight‐chain aliphatic group. Another prerequisite for this solvent‐extraction‐based strategy was the use of thiomalic acid and DBU for Fmoc deprotection, which facilitates the removal of byproducts, such as the fulvene adduct.