1 / 10

OXIDATIVE CYCLIZATIONS OF CYCLIC AMIDINES

OXIDATIVE CYCLIZATIONS OF CYCLIC AMIDINES. Raymond C F Jones , †a James N Iley b & Janet E Smith b a Dept. of Chemistry, Loughborough University, Loughborough, Leics. LE11 3TU, UK b Dept. of Chemistry, The Open University, Walton Hall, Milton Keynes MK7 6AA, UK

najwa
Download Presentation

OXIDATIVE CYCLIZATIONS OF CYCLIC AMIDINES

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. OXIDATIVE CYCLIZATIONSOF CYCLIC AMIDINES Raymond C F Jones,†a James N Ileyb & Janet E Smithb aDept. of Chemistry, Loughborough University, Loughborough, Leics. LE11 3TU, UK bDept. of Chemistry, The Open University, Walton Hall, Milton Keynes MK7 6AA, UK †e-mail r.c.f.jones@lboro.ac.uk; fax: ++44(0)1908223926

  2. Cyclic amidines as pseudopeptides • The use of amide bond replacements is a well-known tactic in the search for agonists or antagonists at peptide receptors. • We have explored cyclic amidines as conformationally restricted amide bond replacements, and have prepared imidazolines (1)1 and TETRAHYDROPYRIMIDINES (2)2 as pseudodipeptides. • 1. R.C.F. Jones and J. Dickson, J. Peptide Sci., 2001, 7, 220, and refs. therein. • 2. R.C.F. Jones and A.K. Crockett, Tetrahedron Lett., 1993, 34, 7459.

  3. Pyoverdins and the tetrahydropyrimidines • We were intrigued to find the tetrahydropyrimidine (THP) amino acids (2) as components of the PYOVERDIN family of yellow-green fluorescent siderophores and of the co-occurring desferriferribactin siderophores found in Pseudomonas bacteria such as P. fluorescens.

  4. Tetrahydropyrimidine amino-acids • We have prepared in protected form some THP amino acids, including some that appear in the pyoverdin and related natural products.2

  5. The chromophore: oxidised THP amino-acid • The Pyoverdin chromophore is also derived from a THP amino-acid after oxidative cyclization, as indicated below. This is consistent with: • co-isolation of siderophores having both uncyclized and cyclized tyrosine-based THP amino-acids (see sheet 3) • isolation of the isopyoverdins, having the isomeric chromophore • isolation of the 5,6-dihydro derivatives.

  6. Model substrates for oxidative cyclisation • To model a biomimetic approach to the chromophore of pyoverdins, we prepared the aryl tetrahydropyrimidine (3) and imidazoline (4).

  7. Oxidation: with a hypervalent iodine reagent • The cyclic amidine substrates (3) and (4) were oxidised in alcohol solvents to give cyclohexadienones, that cyclized on alumina to afford pyrimido and imidazolo[1,2-a]quinolines.

  8. Cyclisation to fused quinolines • X-Ray crystal structures confirm the structures and stereochemistry (cis ring junction) of the 6a-alkoxy-2,3,5,6,6a,9,10,10a-octahydro-1H-pyrimido[1,2-a]quinolin-9-ones.

  9. Aromatisation - the chromophore (nearly!) • Elimination of the “bridgehead” alcohol in strong acid leads to aromatisation of the benzene ring, and the ring system of the chromophore in reduced form, as found in the 5,6-dihydropyoverdins. Dehydrogenation is currently under investigation.

  10. Acknowledgements • We wish to thank the Engineering and Physical Science Research Council and The Open University for funding to JES and for facilities. • We thank the National Service for X-Ray Crystallography (Southampton) for the X-ray crystal structures (Dr Simon Coles) • and the EPSRC National Mass Spectrometry Service Centre (Swansea) for MS data

More Related