Shoji Atsushi, Arai Yuka, Asakawa Ryuki, Saito Tatsuo, Kuramochi Kouji, Yajima Arata
Graduate School of Life Sciences, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, Japan.
Department of Chemistry for Life Sciences and Agriculture, Faculty of Life Sciences, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, Japan.
Biosci Biotechnol Biochem. 2023 Mar 21;87(4):363-370. doi: 10.1093/bbb/zbac212.
The enantioselective synthesis of violaceoid D, a cytotoxic phenolic compound isolated from the culture broth of Aspergillus violaceofuscus Gasperini, was achieved. The total synthesis involves stereoselective construction of the stereogenic center of violaceoid D via Sharpless asymmetric dihydroxylation, followed by Smiles rearrangement. The absolute configuration of natural violaceoid D was determined to be R from the specific rotation value. Synthesized violaceoid D and its analogs were evaluated for cytotoxicity against two human cancer cell lines, Jurkat and HCT116. Because the enantiomer of violaceoid D showed no cytotoxicity, it is plausible that violaceoid D binds selectively to specific target molecules, such as proteins in the cancer cells.
实现了从紫褐曲霉加斯佩里尼培养液中分离得到的具有细胞毒性的酚类化合物紫堇素D的对映选择性合成。全合成过程包括通过夏普莱斯不对称双羟基化反应立体选择性构建紫堇素D的手性中心，随后进行斯迈尔斯重排反应。根据旋光值确定天然紫堇素D的绝对构型为R。对合成的紫堇素D及其类似物针对两种人类癌细胞系Jurkat和HCT116进行了细胞毒性评估。由于紫堇素D的对映体没有显示出细胞毒性，因此紫堇素D可能选择性地与癌细胞中的特定靶分子如蛋白质结合，这是合理的。
