Synthesis of [3-13C]-2,3-dihydroxy-4-methoxybenzaldehyde

doi:10.1016/j.tetlet.2015.12.088

Tetrahedron Letters

Volume 57, Issue 5, 3 February 2016, Pages 563-565

https://doi.org/10.1016/j.tetlet.2015.12.088 Get rights and content

Abstract

An efficient synthesis of [3-¹³C]-2,3-dihydroxy-4-methoxybenzaldehyde, an isotopically labelled probe of a common intermediate used in the synthesis of a number of biologically relevant molecules, has been achieved in 9 steps from an acyclic, non-aromatic precursor. A ¹³C label for molecular imaging was introduced in a linear synthesis from the reaction of [¹³C]-labelled methyl iodide with glutaric monomethyl ester chloride. Cyclisation then aromatisation gave 1,3-dimethoxybenzene and an additional methoxy group was introduced by a formylation/Baeyer–Villiger/hydrolysis/methylation sequence. Subsequent ortho-formylation and selective demethylation yielded the desired [3-¹³C]-2,3-dihydroxy-4-methoxybenzaldehyde.

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Acknowledgments

We thank University of Sheffield A∗STAR programme for funding (R.C.C.), as well as a Programme Grant C1276/A10345 from Cancer Research UK and EPSRC with additional funding from MRC and Department of Health (England).

References and notes (21)

S. Aprile et al.
J. Pharm. Biomed. Anal.
(2013)
M.F. Oldfield et al.
Tetrahedron
(2004)
G.R. Pettit et al.
J. Nat. Prod.
(1987)
G.M. Tozer et al.
Int. J. Exp. Pathol.
(2002)
G. Kremmidiotis et al.
Mol. Cancer Ther.
(2010)
A. Kornienko et al.
Chem. Rev.
(2008)
G.Van Goietsenoven et al.
Med. Res. Rev.
(2013)
M.P. Velcheva et al.
J. Nat. Prod.
(1992)
J. Serkedjieva et al.
Antivir. Chem. Chemother.
(2003)
T.L. Varadinova et al.
Phyther. Res.
(1996)

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We report a method that enables the fast incorporation of carbon isotopes into the ipso carbon of phenols. Our approach relies on the synthesis of a 1,5-dibromo-1,4-pentadiene precursor, which upon lithium–halogen exchange followed by treatment with carbonate esters results in a formal [5 + 1] cyclization to form the phenol product. Using this strategy, we have prepared 12 1-¹³C-labeled phenols, show proof-of-concept for the labeling of phenols with carbon-14, and demonstrate phenol synthesis directly from cyclotron-produced [¹¹C]CO₂.

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Synthesis of [3-13C]-2,3-dihydroxy-4-methoxybenzaldehyde

Abstract

Graphical abstract

Section snippets

Acknowledgments

J. Pharm. Biomed. Anal.

Tetrahedron

J. Nat. Prod.

Int. J. Exp. Pathol.

Mol. Cancer Ther.

Chem. Rev.

Med. Res. Rev.

J. Nat. Prod.

Antivir. Chem. Chemother.

Phyther. Res.

Synthesis of [3-¹³C]-2,3-dihydroxy-4-methoxybenzaldehyde