Biosynthetic and Biomimetic Investigations into Roseophilin

 描述(申请人提供)：自然产生的玫瑰亲和素是自然界中可能发生的前所未有的变化的一个极好的例子。了解生产机制将为以仿生方式复制如此强大的反应性提供重要的见解。虽然玫瑰红素与灵芝红素生物碱的相似性提供了对其生物合成的一些了解，但目前的信息状况不允许制定一条具体的路线。亲红素是从灰色链霉菌中分离出来的，它还产生了与之相关的菌红素R1和去氯玫瑰素。据信指导它们生物合成的基因簇包含四个REG酶的同源物，该酶指导相关化合物链霉菌红素B的环化。因此，假设 这四种酶有助于观察到产生玫瑰素的不寻常的环化事件。为了检测酶的活性，将合成所建议的中间体，二甲基十一烷基灵芝菌素和灵芝菌素R2。合成的中间体将用于喂养实验，以确定酶如何与分子和产生的产品反应。环化事件也将在实验室中通过合成生成据信存在于通往复杂自然结构的关键自由基物种来模拟。氧化条件下灵芝菌素R2的直接反应将被用来筛选该自由基的反应活性，同时还将产生Barton酯类似物，以受控方式直接生成所需的自由基中间体。这些结构的合成将提供推断玫瑰亲油素非凡生物合成所需的重要信息。这一知识将有助于促进未来在仿生碳环化方面的努力，这将被证明是有用的，以一种容易的方式瞄准更复杂的化合物。

 DESCRIPTION (provided by applicant): The natural production of roseophilin is an excellent example of the unprecedented transformations that can occur in nature. Understanding the mechanism of production will provide major insights into reproducing such powerful reactivity in a biomimetic fashion. While the similarity of roseophilin to the prodigiosin alkaloids offers some understanding of its biosynthesis, the current state of information does not allow a concrete route to be formulated. Roseophilin was isolated from the bacterium Streptomyces griseovirdis, which has also produced the related prodigiosin R1 and deschlororoseophilin. The gene cluster believed to direct their biosynthesis contains four homologues of the enzyme RedG, which directs the cyclization of the related compound, streptorubin B. Therefore, it is hypothesized that these four enzymes assist in the unusual cyclization events observed to produce roseophilin. To examine the activity of the enzymes, the proposed intermediates, dimethylundecylprodigiosin and prodigiosin R2, will be synthesized. The synthetic intermediates will be used in feeding experiments to determine how the enzymes react with the molecules and the products that are produced. The cyclization events will also be mimicked in the laboratory by synthetically generating the key radical species believed to exist en route to the complex natural structure. Direct reaction of prodigiosin R2 under oxidative conditions will be used to screen the reactivity of this radical, while a Barton ester analogue will also be produced to directly generate the desired radical intermediate in a controlled fashion. The synthesis of these structures will provide access to vital information needed to deduce the extraordinary biosynthesis of roseophilin. This knowledge will help foster future endeavors in biomimetic carbocyclizations, which will prove useful in targeting more complex compounds in a facile manner.