Synthesis and analysis of bacterial folate metabolism intermediates and antifolates

Surendra Dawadi; Shannon L. Kordus; Anthony D. Baughn; Courtney C. Aldrich

doi:10.1021/acs.orglett.7b02487

Synthesis and analysis of bacterial folate metabolism intermediates and antifolates

Surendra Dawadi, Shannon L. Kordus, Anthony D. Baughn, Courtney C. Aldrich

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

The mechanism of action of para-aminosalicylic acid (PAS), a drug used to treat drug-resistant tuberculosis (TB), has been confirmed through the first synthesis and biochemical characterization of its active metabolite 7. The synthesis features the coupling of N²-acetyl-6-formylpterin obtained from the degradation of folic acid and appropriately functionalized arylamines to form Schiff bases. The sequential chemoselective reduction of the imine and pterin ring led to the formation of dihydrofolate analogue 7 and two other dihydropteroate species.

Original language	English (US)
Pages (from-to)	5220-5223
Number of pages	4
Journal	Organic Letters
Volume	19
Issue number	19
DOIs	https://doi.org/10.1021/acs.orglett.7b02487
State	Published - Oct 6 2017

Bibliographical note

Funding Information:
We thank Dr. Bruce Witthuhn of College of Biological Sciences at the University of Minnesota for technical assistant with LC-MS/ MS method development. This work was financially supported by a grant from the University of Minnesota Academic Health Center Faculty Research Development Program to A.D.B. and C.C.A.

Publisher Copyright:
© 2017 American Chemical Society.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

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AU - Kordus, Shannon L.

AU - Baughn, Anthony D.

AU - Aldrich, Courtney C.

N1 - Funding Information: We thank Dr. Bruce Witthuhn of College of Biological Sciences at the University of Minnesota for technical assistant with LC-MS/ MS method development. This work was financially supported by a grant from the University of Minnesota Academic Health Center Faculty Research Development Program to A.D.B. and C.C.A. Publisher Copyright: © 2017 American Chemical Society. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

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Y1 - 2017/10/6

N2 - The mechanism of action of para-aminosalicylic acid (PAS), a drug used to treat drug-resistant tuberculosis (TB), has been confirmed through the first synthesis and biochemical characterization of its active metabolite 7. The synthesis features the coupling of N2-acetyl-6-formylpterin obtained from the degradation of folic acid and appropriately functionalized arylamines to form Schiff bases. The sequential chemoselective reduction of the imine and pterin ring led to the formation of dihydrofolate analogue 7 and two other dihydropteroate species.

AB - The mechanism of action of para-aminosalicylic acid (PAS), a drug used to treat drug-resistant tuberculosis (TB), has been confirmed through the first synthesis and biochemical characterization of its active metabolite 7. The synthesis features the coupling of N2-acetyl-6-formylpterin obtained from the degradation of folic acid and appropriately functionalized arylamines to form Schiff bases. The sequential chemoselective reduction of the imine and pterin ring led to the formation of dihydrofolate analogue 7 and two other dihydropteroate species.

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Synthesis and analysis of bacterial folate metabolism intermediates and antifolates

Abstract

Bibliographical note

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