Phillips Scott T, Shair Matthew D
Department of Chemistry & Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
J Am Chem Soc. 2007 May 23;129(20):6589-98. doi: 10.1021/ja0705487. Epub 2007 May 1.
The ritterazine class of natural products comprises 26 compounds-all of which are spiroketal-containing steroidal heterodimers-that inhibit the proliferation of cultured human cancer cell lines with IC50 values in the low nanomolar range. Little is known about their chemistry, cellular target(s), or mechanism(s) of growth inhibition, due primarily to the small amount of material available from natural sources. In this paper we report syntheses of the eastern halves of ritterazines B, F, G, and H and address the energetic and mechanistic aspects of spiroketal equilibration for each. These studies have led to reassignment of the 5,5-spiroketal stereochemistry of ritterazines B and F, and they have enabled us to propose a quantitative description of the natural distribution of these ritterazine compounds.
瑞特嗪类天然产物包含26种化合物——所有这些都是含螺缩酮的甾体杂二聚体——它们能抑制培养的人癌细胞系的增殖，其半数抑制浓度（IC50）值在低纳摩尔范围内。由于主要从天然来源获得的材料量很少，人们对它们的化学性质、细胞靶点或生长抑制机制了解甚少。在本文中，我们报道了瑞特嗪B、F、G和H东半部分的合成，并探讨了每种化合物螺缩酮平衡的能量和机理方面。这些研究导致了瑞特嗪B和F的5,5-螺缩酮立体化学的重新归属，并且使我们能够对这些瑞特嗪化合物的天然分布提出定量描述。
