Synthesis of Oxazole Analogs of Streptolidine Lactam

• Published in: European journal of organic chemistry Vol. 2013; no. 32; pp. 7337 - 7342
• Main Authors: Rynearson, Kevin D., Dutta, Sanjay, Tran, Kiet, Dibrov, Sergey M., Hermann, Thomas
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01-11-2013; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Antibiotics; Cycloaddition; Heterocycles; Microbiology; Natural products; RNA recognition
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201300943

The streptolidine lactam is an amino acid constituent of streptothricin antibiotics, which inhibit protein synthesis by targeting the bacterial ribosome but suffer from toxicity as a result of the basicity of the aminoimidazole scaffold in the natural products. On the basis of the streptolidine structure, we designed and synthesized oxazole analogs with six‐ and seven‐membered lactam rings as building blocks for RNA‐targeted ligands. These analogs benefit from a dense network of hydrogen‐bond donors and acceptors within a rigid nonplanar heterocyclic system that has attenuated basicity.
Oxazole analogs based on the streptolidine scaffold of natural RNA‐binding streptothricin antibiotics were designed and synthesized as building blocks for RNA‐targeted ligands. These synthetic analogs with six‐ and seven‐membered lactam rings benefit from a dense network of hydrogen‐bond donors and acceptors within a rigid nonplanar heterocyclic system that has attenuated basicity.