RSS-Feed abonnieren
DOI: 10.1055/s-2004-829561
Methods for the Construction of New Highly Functionalised Guanidines
Publikationsverlauf
Publikationsdatum:
15. Juli 2004 (online)
Abstract
In this study, we present a fast and chemoselective protocol to highly functionalised guanidines. Guanidines containing a hydroxy function were constructed in the microwave by regioselective ring opening of epoxides in the presence of ammonium hydroxide giving the primary amines, which then were reacted with isothiouronium salts. Direct coupling of an unsubstituted guanidine with an epoxide in the presence of n-BuLi gave the same product.
Key words
amino alcohols - epoxides - chemoselectivity - regioselectivity - ring opening
-
1a
Kienzle F.Kaiser A.Madhukar SC. Eur. Med. Chem. 1982, 17: 547 -
1b
Weinhardt K.Wallach MB.Marx M. J. Med. Chem. 1985, 28: 694 -
1c
Rockway TW. Expert Opin. Ther. Patents 2003, 13: 773 -
1d
Chiron Corp. . Expert Opin. Ther. Patents 2003, 13: 551 -
1e
Donnelly LE.Rogers DF. Expert Opin. Ther. Patents 2003, 13: 1345 -
1f
Lehmann J.Rob B. Liebigs Ann. Chem. 1994, 805 -
2a
Marmillon C.Bompart J.Calas M.Escale R.Bonnet P.-A. Heterocycles 2000, 53: 1317 -
2b
Liu F.Lu G.-Y.He W.-J.Mei Y.-H.Zhu L.-G. Synthesis 2001, 4: 607 -
2c
Bruno O.Brullo C.Ranise A.Schenone S.Bondavalli F.Barocelli E.Ballabeni V.Chiavarini M.Tognolini M.Impicciatore M. Bioorg. Med. Chem. Lett. 2001, 11: 1397 -
2d
Linney ID.Buck IM.Harper EA.Kalindjian SB.Pether MP.Shankley NP.Watt GF.Wright PT. J. Med. Chem. 2000, 43: 2362 -
2e For a micro review see:
Manimala JC.Anslyn EV. Eur. J. Org. Chem. 2002, 3909 - 3
Sandin H.Swanstein M.-L.Wellner E. J. Org. Chem. 2004, 69: 1571 -
4a
Plenkiewicz H.Dmowski W. J. Fluorine Chem. 1991, 51: 43 -
4b
Goessnitzer E.Malli R.Schuster S.Favre B.Ryder S. Arch. Pharm. 2002, 11: 535 - 5
Favretto L.Nugent W.Licini G. Tetrahedron Lett. 2002, 43: 2581 - 6
Booth RJ.Hodges JC. J. Am. Chem. Soc. 1997, 119: 4882 - 8
Fahmy HH.Soliman GA. Arch. Pharmacal. Res. 2001, 24: 180 - 9
Chen B.-C.Quinlan SL.Reid JG.Jass PA.Robinson TP.Early WA.Delaney EJ.Humora MJM. Tetrahedron: Asymmetry 1998, 9: 1337
References
Using protected building blocks (path B), the reaction performed less sluggishly leading to a substantially increase in yield.
10NMR spectroscopy indicates also the formation of a by-product with unsymmetrical ring substitution. Attempts to isolate this compound failed.
11The addition of Wang resin ensures the removal of the unreacted isothiouronium salt. This underlines the ambivalent reactivity of the starting material 5 towards alcohols3 and amines under microwave conditions.