Synthesis of Antibiotics

描述(由申请人提供)：这项提案的统一目标是开发有效的合成路线，以获得复杂的抗生素，否则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上。为此，我们将制备一系列具有修饰C和D环的6-脱氧四环素，包括杂环和稠环取代基(例如五环素)。我们现有的6-脱氧四环素路线将进行改进和扩大规模，目标是开发一条能够提供克到公斤新型合成四环素的路线。将探索AB四环素前体的更有效的结构，并将AB和D环前体的收敛偶联进行优化，以得到四环素的ABCD环系，以期开发一条可扩展的、更有效的合成路线。此外，我们将进行基础研究，以探索一种新的大多环化路线的可行性，以生产被称为吡咯西林的新型抗生素。

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.