Cbz,Boc保护氨基酸和脱保护.pdf

ORGANIC LETTERS Synthesis of 2,3- and 3,4-Methanoamino 2008 Vol. 10, No. 16 Acid Equivalents with Stereochemical 3571-3574 Diversity and Their Conversion into the Tripeptide Proteasome Inhibitor Belactosin A and Its Highly Potent Cis-Cyclopropane Stereoisomer Keisuke Yoshida,† Kazuya Yamaguchi,† Takayuki Sone,† Yuka Unno,‡ Akira Asai,‡ Hideyoshi Yokosawa,† Akira Matsuda,† Mitsuhiro Arisawa,† and Satoshi Shuto*,† Faculty of Pharmaceutical Sciences, Hokkaido UniVersity, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan, and Graduate School of Pharmaceutical Sciences, UniVersity of Shizuoka, Yata, Shizuoka 422-8526, Japan shu@pharm.hokudai.ac.jp Received June 13, 2008 ABSTRACT A series of chiral 2,3- and 3,4-methanoamino acid equivalents of stereochemical diversity were designed and synthesized from our chiral cyclopropane units, using a diastereoselective Grignard addition with (R)- or (S)-t-butanesulfinyl imines as the key step. These equivalents were converted into the proteasome inhibitor belactosin A and its cis-cyclopropane stereoisomer. The unnatural cis-isomer was shown to be more than twice as potent as belactosin A as a proteasome inhibitor. The development of useful peptide mimetics may be cyclopropane restricts the conformation of molecules, which achieved by replacing a key amino acid of biologically active