Synthesis-Guided Structure Revision of the Sarcodonin, Sarcoviolin, and Hydnellin Natural Product Family

A sweeping structural revision of the sarcodonin natural product family (published structures 1a−13a) is proposed after extensive studies aimed at their chemical synthesis. Key features of revised structure 1b include replacement of the N,N-dioxide moiety with an oxime, ring-opening of the central diketopiperazine, and transposition of the terphenyl wing from the 1β−2β position of 1a to the 2β−3β position of 1b. This structure revision arose from the serendipitous synthesis of a benzodioxane aminal (44) whose structure was unambiguously determined by X-ray crystallography and whose spectral properties bore considerable resemblance to the published data for the sarcodonins. A versatile new method for O-arylation of hydroxamic acids is also reported herein, as well as a manganese(III)-mediated α-oxidation of hydroxamic acids to aminals.

本研究通过针对齿菌素（sarcodonin）天然产物家族的系统性化学合成研究，提出了该家族已发表结构（1a−13a）的全面结构修正方案。修正后结构1b的核心特征包括：以肟（oxime）基替换原结构中的N,N-二氧官能团（N,N-dioxide moiety）、中心二酮哌嗪（diketopiperazine）环的开环，以及将三联苯（terphenyl）侧翼从1a的1β−2β位转位至1b的2β−3β位。本次结构修正源于苯并二氧六环（benzodioxane）缩胺醛（aminal，44）的意外合成：该化合物的结构经X射线晶体衍射（X-ray crystallography）明确表征，其光谱特性与已发表的齿菌素数据高度吻合。本文同时报道了一种用于羟肟酸（hydroxamic acid）O-芳基化反应的通用新方法，以及一种三价锰（manganese(III)）介导的羟肟酸α-氧化制备缩胺醛的反应。