Total synthesis of calyculin C
Total synthesis of calyculin C
复制标题
DOI：
10.1021/ja980836q
复制
发表时间：
1998-12-09
影响因子：
15
通讯作者：
Armstrong, RW
中科院分区：
文献类型：
--
作者：
Ogawa, AK;Armstrong, RW
磷酸酶的研究继续蓬勃发展，因为它们在信号转导途径和细胞功能调节中的突出地位。我们在这一领域的研究工作集中在丝氨酸/苏氨酸磷酸酶，PP 1和PP 2A的有效抑制，由结构多样的天然产物类。我们在此报道丝氨酸/苏氨酸磷酸酶抑制剂calyculin C（1）的全合成，作为正在进行的努力的一部分，以阐明上述不同类别的天然产物对磷酸酶抑制的关键结构要求。所解决的合成问题包括（）在引入C-10-C-11立体中心期间，远程保护基团对棕色巴豆基硼化非对映选择性的影响和（2）使用完全脱保护的C-26-C-37 鏻盐（3）形成C-25-C-26双键。此外，R-34-calyculin C（29）的同时合成澄清了我们先前对C26-C37 鏻盐（3和27）的C-34-立体化学分配（Ogawa，A. K.的; DeMattei，J. A.;斯卡拉托湾的R.; Tellew，J. E.;冲湖S.的;阿姆斯特朗河W. 1996，61，6153）。
The study of phosphatases continues to flourish given their prominence in signal transduction pathways and the regulation of cell function. Our research efforts in this area focus on the potent inhibition of serine/threonine phosphatases, PP1 and PP2A, by a structurally diverse class of natural products. We herein report the completed total synthesis of the serine/threonine phosphatase inhibitor calyculin C (1) as part of an ongoing effort to elucidate key structural requirements for phosphatase inhibition by the aforementioned diverse class of natural products. Synthetic issues addressed include () the remote protecting group effect on Brown crotylboration diastereoselectivity during the introduction of the C-10-C-11 stereocenters and (2) the formation of the C-25-C-26 double bond using a fully deprotected C-26-C-37 phosphonium salt (3). In addition,the concurrent synthesis of R-34-calyculin C (29) clarified our previous C-34-stereochemical assignment of C26-C37 phosphonium salts (3 and 27) (Ogawa, A. K.; DeMattei, J. A.; Scarlato, G. R.; Tellew, J. E.; Chong, L. S.; Armstrong, R. W. J. Org. Chem. 1996, 61, 6153).