The synthesis and crystal structure of alpha-keto tetrazole-based dipeptide mimics

doi:10.1016/S0040-4039(01)01101-7

Tetrahedron Letters

Volume 42, Issue 33, 13 August 2001, Pages 5641-5644

https://doi.org/10.1016/S0040-4039(01)01101-7 Get rights and content

Abstract

Here we report the synthesis of a cis-dipeptide mimic N-Boc-Phe-[COCN₄]-Gly-OBn, 7, containing the non-hydrolysable α-keto tetrazole isostere and an unusual 2,5-disubstituted α-keto tetrazole-based peptidomimetic, 8. The incorporation of the novel cis-amide bond isostere was achieved via direct alkylation of a precursor five-substituted (1H)-tetrazole. The assignment of the resulting 1,5- and 2,5-tetrazoyl regiomers was based on the first reported X-ray structure analysis of an α-keto tetrazole, compound 8.

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Acknowledgments

The work was supported by a Royal Society of New Zealand Marsden grant.

References (19)

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In medicinal chemistry, they are utilized as bioisosteres because the tetrazole rings can act as a biological equivalent to a carboxyl group and cis-amide [2]; this functionality has been applied in antihypertensive [3] and antiplatelet agents [4]. Tetrazoles have also been used in materials science [5] and as ligands in coordination chemistry [6]. Although various tetrazole synthesis methods have been developed [7], synthesis is usually performed by the [3 + 2]-cycloaddition reaction between nitriles and azides.
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The principal goal of this research is to provide a detailed study of various modified/unmodified clays as catalysts/promoters for green synthesis of diverse biologically active molecules. The application of naturally occurring clays provides several advantages such as environmentally friendly procedure, short reaction times, multiple catalytic recycling as well as the benefits of solvent-free conditions, excellent yields, and easy work-up methodology. Therefore, it is a valuable procedure from the viewpoint of green chemistry. This paper also includes clay-mediated synthetic approaches for various pharmaceutically important heterocycles such as azo dyes, i.e., 4-(1,3-benzoxazol-2-yl) aniline, indolinones, bismaleimides and bisphthalimides, α-aminonitriles, poly(d,l-Lactide), biscoumarins, tetrazoles, 4-dihydropyrimidin-2(1H)-ones, and trans-chalcones along with other products of interests.
Survey reactivity of 5-substituted tetrazoles toward pentafluoropyridine
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Their reaction with various electrophiles introduced a broad range of substituents such as alkyl, aryl, vinyl, sulfonyl, silyl, acyl and phosphoryl groups on the tetrazole ring [6]. The main defect of 5-substituted tetrazole reactions is attributed to the low regioselectivity of substitution that eventuated to a mixture of both 1- and 2-substituted products, whereas the ratio of isomers depended on the reaction temperature as well as substituents located at the 5-position [5–15]. These revealed that electron-accepting substituents at the 5-position enhance the formation of 2-isomer, while high reaction temperature increased the amount of 1-isomer.
Reactivity of some 5-substituted tetrazoles with pentafluoropyridine under basic conditions in acetonitrile was investigated. The reaction of pentafluoropyridine with tetrazoles regioselectively occurs at the 4-position of pyridine ring by N2 in the tetrazole ring. Tetrazoles with substituents at the position 5 such as Ph, 4-NO₂C₆H₄, 4-CF₃CONHC₆H₄, 4-ClC₆H₄CH₂, EtOOCCH₂, and 5-tetrazolyl−CH₂ gave products containing unchanged tetrazole moiety. In contrast, tetrazole with substituents at the position 5 such as 3-(5-tetrazolyl)C₆H₄, 4-MeOC₆H₄, and 3-CF₃CONHC₆H₄, gave hydrazide products via degradation of tetrazole ring.

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The synthesis and crystal structure of alpha-keto tetrazole-based dipeptide mimics

Abstract

Section snippets

Acknowledgments

J. Chem. Soc., Perkin Trans. 1

J. Am. Chem. Soc.

J. Med. Chem.

Bioorg. Med. Chem. Lett.

J. Med. Chem.

J. Am. Chem. Soc.

J. Org. Chem.