The convergent total synthesis and antibacterial profile of the natural product streptothricin F

Matthew G. Dowgiallo; Brandon C. Miller; Mintesinot Kassu; Kenneth P. Smith; Andrew D. Fetigan; Jason J. Guo; James E. Kirby; Roman Manetsch

doi:10.1039/D1SC06445B

The convergent total synthesis and antibacterial profile of the natural product streptothricin F†

Matthew G. Dowgiallo,

^a Brandon C. Miller,

^a Mintesinot Kassu,^a Kenneth P. Smith,^ef Andrew D. Fetigan,^a Jason J. Guo,^acd James E. Kirby

^ef and Roman Manetsch

*^abc

Author affiliations

* Corresponding authors

^a Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA
E-mail: r.manetsch@northeastern.edu

^b Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, USA

^c Center for Drug Discovery, Northeastern University, Boston, MA, USA

^d Barnett Institute for Chemical and Biological Analysis, Northeastern University, Boston, MA, USA

^e Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA

^f Harvard Medical School, Boston, MA, USA

Abstract

A convergent, diversity-enabling total synthesis of the natural product streptothricin F has been achieved. Herein, we describe the potent antimicrobial activity of streptothricin F and highlight the importance of a total synthesis that allows for the installation of practical divergent steps for medicinal chemistry exploits. Key features of our synthesis include a Burgess reagent-mediated 1,2-anti-diamine installation, diastereoselective azidation of a lactam enolate, and a mercury(II) chloride-mediated desulfurization-guanidination. The development of this chemistry enables the synthesis and structure–activity studies of streptothricin F analogs.

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DOI: https://doi.org/10.1039/D1SC06445B
Article type: Edge Article
Submitted: 18 Nov 2021
Accepted: 16 Feb 2022
First published: 25 Feb 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry

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Chem. Sci., 2022,13, 3447-3453

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The convergent total synthesis and antibacterial profile of the natural product streptothricin F

M. G. Dowgiallo, B. C. Miller, M. Kassu, K. P. Smith, A. D. Fetigan, J. J. Guo, J. E. Kirby and R. Manetsch, Chem. Sci., 2022, 13, 3447 DOI: 10.1039/D1SC06445B

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Chemical Science

The convergent total synthesis and antibacterial profile of the natural product streptothricin F†

Abstract

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The convergent total synthesis and antibacterial profile of the natural product streptothricin F

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