Total Synthesis - Partly Including the 3D-Assignments of Hitherto Unknown Stereocenters - of 3-(Polyenoyl)tetramic Acid and 3 (Polyenoyl)hydroxypyridone Natural Products: Militarinones, Farinosone B, Fumosorinone, and two Anomeric Aurantosides

四羧酸是5元酮内酰胺、活性亚甲基化合物和弱酸（pKa 6.4）。3-（聚烯醇）四酸是活性的甲烷化合物和较强的酸（pKa 3.4）。后一种类型的四种天然化合物属于我们的合成目标。此外，我们计划合成类似的6元酮内酰胺天然产物（五个靶点）和模型化合物（两个靶点），每个靶点都有一个3-聚烯基。这些化合物应该是芳香的或非芳香的，并显示一个N-H或N-OH基序。它们可以被归类为3-（聚乙烯基）羟基吡啶酮。3-（聚烯基）四酸是抗生素、抗病毒药物、细胞毒和/或杀菌剂。这使得它们与制药和作物保护相关。3-（聚烯醇）羟基吡啶酮影响神经系统的信号转导。因此，它们代表了对破坏神经细胞的疾病（阿尔茨海默病、帕金森病、脊髓损伤）进行化疗的线索。我们的一个主要目标是（继续）发展有效的综合方法。首先，含溴烯烃的ß-酮硫酯应该是3-（聚烯基）四酸和羟基吡啶酮的中心三功能构建块。在这方面，我们感到鼓舞的是，在我们的结构阐明的3-（多烯基）四羧酸a-和ß-脂霉素的总合成中首次使用这样的构建块。其次，两个靶分子基团的杂环是由Dieckmann凝聚形成的。由此从ß-酮酰化a-氨基酸酯得到5元酰基酮酸酯是众所周知的。相比之下，从ß-酮酰化ß-氨基或ß-（羟氨基）酸酯中获得6元酰基酮酸酯的研究要少得多。此外，某些β -（羟氨基）酸酯将由异恶唑烷酮制备。含有基序C(= O)-O-N，后者是非环Weinreb酰胺。实际上，我们对它们的烯化化学一无所知。只是它可能很符合我们的目标。另一个主要目标是建立或完成七个目标分子的三维结构，其构型尚不（完全）已知。为了阐明它们，我们打算合成每一种此类化合物的对映体纯非对映体，其数量必须使一个非对映体的比旋绝对值等于已发表的值。比较旋转的符号就会得到构型。军事甾体A-C和D-E在lemiex - johnson条件下通过降解其三烯侧链来澄清其甲基化立体中心的构型。这就产生了具有顺式取向的甲基对的醇。它们的立体结构应该与对映异构参考样品（反过来，应源于合成）进行气相色谱比较。我们在培养链霉菌、分离a-脂霉素、氧化降解以及（三氟乙酰）化后产生的醇的过程中获得了基础技术方面的专业知识。

Tetramic acids are 5-membered ketolactams, active methylene-compounds, and weak acids (pKa 6.4). 3-(Polyenoyl)tetramic acids are active methine-compounds and stronger acids (pKa 3.4). Four natural compounds of the latter type belong to our synthetic goals. Moreover, we plan to synthesize analogous 6-membered ketolactam natural products (five targets) and model compounds (two targets), each with a 3-polyenoyl group. These compounds shall be aromatic or non-aromatic and display an N-H or N-OH motif. They can be binned as 3-(polyenoyl)hydroxypyridones.3-(Polyenoyl) tetramic acids are antibiotics, antivirals, cytotoxics and/or fungicides. This makes them relevant for pharmacy and crop protection. 3-(Polyenoyl)hydroxypyridones affect signal transduction in the nervous system. Therefore, they represent leads for the chemotherapy of diseases destroying nerve cells (Alzheimer's, Parkinson's, injuries of th spinal cord).A main objective of ours is (continuing) the development of efficient synthetic methodology. Firstly, bromoolefin-containing ß-ketothioesters shall be the central trifunctional building block both of 3-(polyenoyl)tetramic acids and hydroxypyridones. We feel encouraged in this regard by the first-time use of such a building block in our structure-elucidating total synthesis of the 3-(polyenoyl)tetramic acids a- and ß-lipomycin. Secondly, the heterocycle of both target molecule groups shall result from Dieckmann condensations. Reaching 5-membered acylketolactames thereby from ß-ketoacylated a-amino acid esters is well-known. In contrast, reaching 6-membered acylketolactames thereby from ß-ketoacylated ß-amino- or ß-(hydroxyamino)acid esters is much less studied. Moreover, certain ß-(hydroxyamino)acid esters shall be prepared from isoxazolidinones. Containing the motif C(= O)-O-N, the latter are no cyclic Weinreb amides. Virtually nothing is known about their enolate chemistry. Just it might serve our objectives well, though.Another main objective is establishing or completing the 3D structure of the seven target molecules, whose configurations are not (fully) known. For elucidating them, we intend to synthesize enantiomerically pure diastereomers of each such compound in such numbers that the absolute value of the specific rotation of one diastereomer must equal the published value. Comparing signs of rotation will then yield the configuration.The militarinones A-C and D-E suggest to have the configuration of their methylated stereocenters clarified by degrading hteir trienoyl side-chain under Lemieux-Johnson conditions. This should deliver alcohols with a syn-oriented pair of methyl groups. Their stereostructure should yield to GC comparisons with pairs of enantiomorphic reference samples (which, in turn, shall stem from synthetis). We acquired expertise in the underlying techniques when cultivating Streptomyces, isolating a-lipomycin, degrading it oxidatively, and GC-ing the resulting alcohols after (trifluoroacetyl)ation.