Lewis acid-mediated rearrangement of 4-imino-4H-3,1-benzoxazins : total synthesis of pyrazino[2,1-b]quinazoline-3,6-diones on solid support

• Main Authors: Wei-Chung Chuang, 莊維仲
• Other Authors: Yen-ho Chu
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/04011786751263321864

碩士 === 國立中正大學 === 化學所 === 96 === Abstract Alkaloid pyrazino[2,1-b]quinazoline-3,6-diones contain structural motifs of quinazolinone and diketopiperazine-like skeletons. Some of which were found to have bioactivities. The last two steps in the organic synthesis of alkaloid pyrazino[2,1-b]quinazoline-3,6-diones involve the synthesis of peptides, which then undergo a cyclization-upon-deprotection reaction to form the final product. To perform peptide synthesis and cyclization-upon-deprotection, our and other laboratories have traditionally used liquid phase peptide synthesis and a combination of triphenylphosphine, iodine, and diisopropylethylamine (DIEA), respectively. Here we propose a new strategy to complete the synthesis of alkaloid pyrazino[2,1-b]quinazoline-3,6-diones. To successfully synthesize the required peptides, we demonstrate that a different technique named solid-phase-peptide synthesis (SPPS) may be used. To successfully perform the final step of cyclization, we found that various Lewis acids could be used, with the most efficient Lewis acid being Zn(OTf)2. Our results showed that Zn(OTf)2 shortened the cyclization from what would otherwise take normally a few days to hours to complete. By using our novel approach involving SPPS and Lewis acids, pyrazino[2,1-b]quinazoline-3,6-diones libraries may be established more rapidly and applied in bioactivity assays in the future.