Journal of the Chemical Society Perkin Transactions 1 · 1987 · 36 citations · 0 references
PharmacyMedicinal ChemistryPharmacologyDrug DiscoveryOrganic ChemistrySynthetic Medicinal ChemistryEnzyme InhibitionHeterocycle SynthesisHeterocyclic ChemistryOrganic SynthesisPhosphodiester Bond ChemistryHeterocyclic Medicinal ChemistryIndole ChemistryIndole SynthesisMedicinal Chemistry ApplicationsMedicinal HeterocyclesPhosphodiesterase InhibitionPyrrole ChemistryPyrrole Synthesis
The synthesis of the naturally occurring pyrrolo[3,2-e]indole phosphodiesterase inhibitors PDE-I (1) and PDE-II (2) from isovanillin is described. The route involves the construction of both pyrrole rings by vinylnitrene cyclisations, the key cyclisation substrates being the azidoacrylates (5) and (11), prepared from the aldehydes (4) and (10) respectively. The tricyclic intermediate (12) is converted into both PDE-I and PDE-II by selective reduction, followed by carbamoylation or acetylation respectively, and deprotection.