Synthesis of Antibiotics

描述（由申请人提供）：本提案的统一目标是开发复杂抗生素的有效合成途径，否则这些结构将无法进行研究和评估。我们的工作主要集中在新型四环素类抗生素的合成和评价。为此，我们将制备各种具有修饰C和D环的6-脱氧四环素，包括杂环和融合环取代基（例如，五环素）。我们现有的6-脱氧四环素的路线将被改进和扩展，目标是开发一条能够提供克到公斤的新型合成四环素的路线。我们将探索更高效的AB型四环素前体结构，并再次优化AB与d环前体的收敛耦合，形成ABCD型四环素环体系，以期找到一条可扩展、更高效的合成路线。此外，我们将进行基础研究，探索一种新的大多环化路线的可行性，以生产新型抗生素，称为吡啶类。

DESCRIPTION (provided by applicant): The unifying goal of this proposal is to develop efficient synthetic routes to complex antibiotics, structures that would otherwise be inaccessible for study and evaluation. The primary focus of our work is on the synthesis and evaluation of novel tetracycline antibiotics. Toward this end, we will prepare an extraordinary variety of 6-deoxytetracyclines with modified C and D rings, including heterocycles and fused-ring substituents (e.g., pentacyclines). Our existing route to 6-deoxytetracyclines will be refined and scaled, with the goal of developing a route capable of providing grams to kilograms of novel synthetic tetracyclines. More efficient constructions of AB tetracycline precursors will be explored, and the convergent coupling of AB and D-ring precursors to give the ABCD ring system of the tetracyclines will be optimized, again, with a view to developing a scalable, more efficient synthetic route. In addition, we will undertake basic studies to explore the feasibility of a novel macropolycyclization route to produce the new class of antibiotics known as the pyrrocidines.