Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019;23(9):978-993.
doi: 10.2174/1385272823666190424142821.

Methods for Hydroxamic Acid Synthesis

Mohammad A Alam  1
Affiliations

Methods for Hydroxamic Acid Synthesis

Mohammad A Alam. Curr Org Chem. 2019.

Abstract

Substituted hydroxamic acid is one of the most extensively studied pharmacophores because of their ability to chelate biologically important metal ions to modulate various enzymes, such as HDACs, urease, metallopeptidase, and carbonic anhydrase. Syntheses and biological studies of various classes of hydroxamic acid derivatives have been reported in numerous research articles in recent years but this is the first review article dedicated to their synthetic methods and their application for the synthesis of these novel molecules. In this review article, commercially available reagents and preparation of hydroxylamine donating reagents have also been described.

Keywords: Hydroxamic acids; catalytic reaction; coupling reactions; direct synthesis; hydroxy lamine; mutagens.

PubMed Disclaimer

Conflict of interest statement

CONFLICT OF INTEREST The author declares no conflict of interest, financial or otherwise.

Figures

Fig. 1.
Fig. 1.
Approved hydroxamic acid based drugs.
Fig. 2.
Fig. 2.
Under clinical trials hydroxamic acid derivatives (5–9) [51] and a potent HDAC6 inhibitor (10) [50].
Fig. 3.
Fig. 3.
Commonly available hydroxylamine donors.
Scheme 1.
Scheme 1.
Synthesis of hydroxylamine donors.
Scheme 2.
Scheme 2.
Direct reaction of hydroxylamine with esters derivatives.
Scheme 3.
Scheme 3.
Reaction of hydroxylamine with esters under catalytic condition and microwave irradiation.
Scheme 4.
Scheme 4.
Reaction of hydroxylamine with activated carboxylic acids.
Scheme 5.
Scheme 5.
THPONH2 (20) for hydroxamic acid synthesis.
Scheme 6.
Scheme 6.
Synthesis of hydroxamic acids by using O-tritylhydroxylamine.
Scheme 7.
Scheme 7.
Solid supported synthesis of hydroxamic acids.
Scheme 8.
Scheme 8.
Use of PMBONH2 and BnONH2 for hydroxamic acid synthesis.
Scheme 9.
Scheme 9.
O-Silyl hydroxylamines for hydroxamic acid synthesis.
Scheme 10.
Scheme 10.
Miscellaneous methods.
See this image and copyright information in PMC

References

    1. Neff C; Bellot F; Waern JB; Lambert F; Brandei J; Serratrice G; Gaboriau F; Policar C, Glycosiderophores: Synthesis of tris-hydroxamate siderophores based on a galactose or glycero central scaffold, Fe(III) complexation studies. J. Inorg. Biochem, 2012,112, 59–67. - PubMed
    1. Codd R, Traversing the coordination chemistry and chemical biology of hydroxamic acids. Coord. Chem. Rev, 2008, 252, 1387–1408.
    1. Griffith DM; Szocs B; Keogh T; Suponitsky KY; Farkas E; Buglyo P; Marmion CJ, Suberoylanilide hydroxamic acid, a potent histone deacetylase inhibitor; its X-ray crystal structure and solid state and solution studies of its Zn(II), Ni(II), Cu(II) and Fe(III) complexes. J. Inorg. Biochem, 2011,705,763–9. - PubMed
    1. Locock KES; Yamamoto I; Tran P; Hanrahan JR; Chebib M; Johnston GAR; Allan RD, γ-Aminobutyric Acid(C) (GABAC) Selective antagonists derived from the bioisosteric modification of 4-aminocyclopent-1-enecarboxylic acid: Amides and Hydroxamates. J. Med. Chem, 2013, 56, 5626–5630. - PubMed
    1. Flipo M; Charton J; Hocine A; Dassonneville S; Deprez B; Deprez-Poulain R Hydroxamates: relationships between structure and plasma stability. J. Med. Chem, 2009, 52, 6790–802. - PubMed

LinkOut - more resources