Keck Gary E, Kraft Matthew B, Truong Anh P, Li Wei, Sanchez Carina C, Kedei Noemi, Lewin Nancy E, Blumberg Peter M
Department of Chemistry, University of Utah, 315 South 1400 East, RM 2020, Salt Lake City, Utah 84112, USA.
J Am Chem Soc. 2008 May 28;130(21):6660-1. doi: 10.1021/ja8022169. Epub 2008 May 2.
Highly potent bryostatin analogues which contain the complete bryostatin core structure have been synthesized using a pyran annulation approach as a key strategic element. The A ring pyran was assembled using a pyran annulation reaction between a C1-C8 hydroxy allylsilane and an aldehyde comprising C9-C13. This pyran was transformed to a new hydroxy allylsilane and then coupled with a preformed C ring aldehyde subunit in a second pyran annulation, with concomitant formation of the B ring. This tricyclic intermediate was elaborated to bryostatin analogues which displayed nanomolar to subnanomolar affinity for PKC, but displayed properties indistinguishable from a phorbol ester in a proliferation/attachment assay.
已使用吡喃环化方法作为关键战略要素合成了含有完整苔藓抑素核心结构的高效苔藓抑素类似物。A环吡喃是通过C1-C8羟基烯丙基硅烷与包含C9-C13的醛之间的吡喃环化反应组装而成。该吡喃被转化为新的羟基烯丙基硅烷，然后在第二次吡喃环化反应中与预先形成的C环醛亚基偶联，同时形成B环。该三环中间体被进一步修饰为苔藓抑素类似物，其对蛋白激酶C显示出纳摩尔至亚纳摩尔的亲和力，但在增殖/附着试验中显示出与佛波酯无法区分的性质。
