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. 2022 Feb 25;13(12):3447-3453.
doi: 10.1039/d1sc06445b. eCollection 2022 Mar 24.

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

Matthew G Dowgiallo  1 , Brandon C Miller  1 , Mintesinot Kassu  1 , Kenneth P Smith  2   3 , Andrew D Fetigan  1 , Jason J Guo  1   4   5 , James E Kirby  2   3 , Roman Manetsch  1   6   4
Affiliations

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

Matthew G Dowgiallo et al. Chem Sci. .

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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Conflict of interest statement

The authors declare no competing financial interest. The HP D300 digital dispenser and TECAN M1000 used for MIC analysis in Table 1 were provided for our use by TECAN (Morrisville, NC). TECAN had no role in study design, data collection/interpretation, manuscript preparation, or decision to publish.

Figures

Fig. 1
Fig. 1. Structures of the streptothricins A–F, and X. The streptolidine lactam is shown in red, the gulosamine core is shown in black, and the β-lysine homopolymer is shown in blue.
Scheme 1
Scheme 1. Retrosynthetic analysis of streptothricin F (1).
Scheme 2
Scheme 2. Synthesis of streptolidine isothiocyanate 3.
Scheme 3
Scheme 3. Synthesis of the gulosamine 7.
Scheme 4
Scheme 4. The convergent total synthesis of streptothricin F.
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