Medicinal Chemistry, Taros Chemicals GmbH & Co. KG, Emil-Figge-Straße 76a, 44227 Dortmund, Germany.
Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy.
Molecules. 2018 Oct 6;23(10):2545. doi: 10.3390/molecules23102545.
Resistance to antibiotics is an increasingly serious threat to global public health and its management translates to significant health care costs. The validation of new Gram-negative antibacterial targets as sources for potential new antibiotics remains a challenge for all the scientists working in this field. The interference with bacterial Quorum Sensing (QS) mechanisms represents a potentially interesting approach to control bacterial growth and pursue the next generation of antimicrobials. In this context, our research is focused on the discovery of novel compounds structurally related to ()-4,5-dihydroxy-2,3-pentanedione, commonly known as ()DPD a small signaling molecule able to modulate bacterial QS in both Gram-negative and Gram-positive bacteria. In this study, a practical and versatile synthesis of racemic DPD is presented. Compared to previously reported syntheses, the proposed strategy is short and robust: it requires only one purification step and avoids the use of expensive or hazardous starting materials as well as the use of specific equipment. It is therefore well suited to the synthesis of derivatives for pharmaceutical research, as demonstrated by four series of novel DPD-related compounds described herein.
抗生素耐药性是对全球公共卫生的日益严重威胁，其管理转化为重大的医疗保健成本。验证新的革兰氏阴性抗菌靶标作为潜在新抗生素的来源，对所有从事该领域工作的科学家来说仍然是一个挑战。干扰细菌群体感应（QS）机制代表了一种控制细菌生长和追求下一代抗菌药物的潜在有趣方法。在这种情况下，我们的研究重点是发现与（）-4,5-二羟基-2,3-戊二酮结构相关的新型化合物，通常称为（）DPD，这是一种能够调节革兰氏阴性和革兰氏阳性细菌中细菌 QS 的小分子信号分子。在这项研究中，提出了一种实用且通用的外消旋 DPD 合成方法。与以前报道的合成方法相比，所提出的策略简短而稳健：它只需要一个纯化步骤，避免使用昂贵或危险的起始材料以及使用特殊设备。因此，它非常适合用于药物研究的衍生物合成，正如本文所述的四个系列新型 DPD 相关化合物所证明的那样。
