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. 2015 Oct 16;80(20):10076-85.
doi: 10.1021/acs.joc.5b01703. Epub 2015 Sep 24.

Synthesis of Naamidine A and Selective Access to N(2)-Acyl-2-aminoimidazole Analogues

Joseph B Gibbons  1 , Justin M Salvant  1 , Rachel M Vaden  1 , Ki-Hyeok Kwon  1 , Bryan E Welm  2 , Ryan E Looper  1
Affiliations

Synthesis of Naamidine A and Selective Access to N(2)-Acyl-2-aminoimidazole Analogues

Joseph B Gibbons et al. J Org Chem. .

Abstract

A short and scalable synthesis of naamidine A, a marine alkaloid with a selective ability to inhibit epidermal growth factor receptor (EGFR)-dependent cellular proliferation, has been achieved. A key achievement in this synthesis was the development of a regioselective hydroamination of a monoprotected propargylguanidine to deliver N(3)-protected cyclic ene-guanidines. This permits the extension of this methodology to prepare N(2)-acyl analogues in a fashion that obviates the troublesome acylation of the free 2-aminoimidazoles, which typically yields mixtures of N(2)- and N(2),N(2)-diacylated products.

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Conflict of interest statement

Notes The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Representative Leucetta alkaloids.
Figure 2
Figure 2
X-ray structures of 18b and 20h.
Figure 3
Figure 3
Antiproliferative effects of naamidine A and 20h.
Scheme 1
Scheme 1
First Generation Synthesis of Naamidine A and Analogues
Scheme 2
Scheme 2
Synthesis of Naamidine A (6)
Scheme 3
Scheme 3
Generation of N2-Acyl Naamidine A Analogues
Scheme 4
Scheme 4
Generation of N2-Acyl-2-aminoimidazoles
See this image and copyright information in PMC

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