Solid-Phase Synthesis of 3-AminopyrroIe-2,5-dicarboxylate Analogues

摘要

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.