Synthesis Of N-alkyl-1 H-pyrrole Compounds With Potential Inhibition Of HIV-1 Gp41

N-alkyl-lH-pyrrole compounds are an important class of drug intermediates, which not only have been found in two compounds of RNase H (Ribonuclease H) inhibitors, but also are the potential HIV-1 gp41 inhibitors. In this paper, the multi-step cascade reaction of trans-4-hydroxy-L-proline with aldehydes has been developed to prepare N-alkyl-lH-pyrrole compounds. We think that it has occurred amination, decarboxylation reaction, hydroxyl elimination reaction and their oxidation-reduction/aromatization reaction.The yields of target compounds using one-pot method are generally low, while dropping method makes the yields of target compounds improved significantly. So the dropping method of the reaction conditions were optimized to establish the optimal reaction conditions as below:the feed ratio of trans-4-hydroxy-L-proline and aldehydes is 1:1.5, DMF is solvent,10% molar ratio of acetic acid is a catalyst and heat to reflux for 10min.Using this method,21 compounds have been synthesized, where 5 compounds have not been reported in the literature. The yields of target compounds of aromatic aldehydes were higher than 80%, except that the yield of target compound of 2-fluorobenzaldehyde is 77%; the yields of target compounds of aliphatic aldehydes are between 70-80%.