Total Synthesis of Natural Products with Antimicrobial Activity

• Main Author: Giltrap, Andrew (Author, http://id.loc.gov/vocabulary/relators/aut)
• Corporate Author: SpringerLink (Online service)
• Format: Electronic eBook
• Language: English
• Published: Singapore : Springer Singapore : Imprint: Springer, 2018.
• Edition: 1st ed. 2018.
• Series: Springer Theses, Recognizing Outstanding Ph.D. Research,
• Subjects: Medicinal chemistry.; Medical biochemistry.; Drug resistance.; Medicinal Chemistry.; Medical Biochemistry.; Drug Resistance.

 This thesis focuses on the development of efficient and scalable total syntheses of natural products that can be used as preferred scaffolds for anti-infective drug discovery. It describes the total synthesis of two classes of antimicrobial non-ribosomal peptides (NRPs) - teixobactin and the skyllamycins - with subsequent biological evaluation. The first part describes the first total synthesis of teixobactin by means of a solid-phase peptide synthesis-macrolactamisation approach, yielding a synthetic natural product that can combat a number of clinically relevant Gram-positive bacterial pathogens. The second part describes the first total synthesis of skyllamycins A-C, a family of structurally complex cyclic NRPs, which inhibit the growth of the Pseudomonas aeruginosa biofilms that are responsible for significant mortality among cystic fibrosis patients. 

 Introduction -- Total Synthesis of Teixobactin -- Synthesis of Deshydroxy Skyllamycins A-C -- Total Synthesis of Skyllamycins A-C -- Experimental.