Solid-phase synthesis of 3-aminopyrrole-2,5-dicarboxylate analogues.
An efficient strategy has been developed for the solid-phase parallel synthesis of 3-aminopyrrole-2,5-dicarboxylate analogues. A library of twenty-nine 2,3,5-trisubstituted pyrroles has been synthesized on Wang resin by a 5-6 step process. The attachment of (2S,4R)-4-hydroxy-N-(PhF)proline cesium salt (PhF = 9-(9-phenylfluorenyl)) to Wang bromide resin, followed by alcohol oxidation, produced the resin-bound 4-oxo-N-(PhF)prolinate as the pyrrole precursor. Resin-bound 3-aminopyrroles were synthesized by treatment of the oxo-N-(PhF)prolinate resin with different secondary amines and diversified at the 2-position by acylation with trichloroacetyl chloride and haloform reactions with primary amines. 3-Aminopyrrole-2,5-dicarboxylates were isolated in 81-99% purity and 51-99% yields after cleavage from the resin using TFA or sodium methoxide.
Brouillette
Yann
Y
Département de Chimie, Université de Montréal, C.P. 6128, Succursale Centre Ville, Montréal, Québec, Canada H3C 3J7.
Rombouts
Frederik J R
FJ
Lubell
William D
WD
D000588:Amines / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D006909:Hydroxyproline / Q000737:chemistry*; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D012117:Resins, Synthetic / Q000737:chemistry*
D000588:Amines; D011758:Pyrroles; D012117:Resins, Synthetic; D006909:Hydroxyproline