A modular, scalable, chemical synthesis platform that produces new Streptogramin A class antibiotic candidates.
In the U.S., at least 2 million people get an antibiotic-resistant infection each year, of which nearly 23,000 people die (CDC - AR Threats Report, 2013). The global antibiotic resistance market was valued at USD 7.81 billion in 2017 and is growing rapidly. Streptogramin antibiotics are used clinically to treat multidrug-resistant bacterial infections but their poor physicochemical properties and narrow spectra of activity have limited their utility.
Researchers at UCSF have created modular, scalable, synthesis platform for group A streptogramin antibiotics that proceeds in 6–8 linear steps from simple chemical building blocks. The versatile structural optimization obtained by using this fully synthetic synthesis allows for overcoming the inherent limitations of streptogramin antibiotics produced by fermentation as well as to combat growing resistance to the class. This platform has the following advantages:
Researchers at University of California, San Francisco have created a novel fully synthetic platform for synthesis of streptogramin A antibiotics. This method is enabled by convergent assembly of simple chemical building blocks. Four such blocks are used to build the “left half” of the analog and three blocks for the “right half” by a sequence of less than 4 steps. The two halves are then coupled to a final antibiotic candidate in 3 steps. This platform is able to generate a library of antibiotic candidates with structural variability that can improve and expand their activity and pharmacological properties. Work is in progress to develop and test several new antibiotic candidates with novel compositions of matter.
Proof of Concept
In vitro data
Streptogramin A antibiotic synthesis, Synthesis platform