Microwave-Assisted Synthesis and Antileishmanial Activity of 3-methoxycarbonyl-γ-butyrolactone Derivatives

We describe the microwave-assisted synthesis of ten 3-methoxycarbonyl-gamma-butyrolactone derivatives and evaluate their in vitro antileishmanial activity against promastigote forms of Leishmania amazonensis. The synthesis furnished most of the compounds in 80-95% yield and reactions lasted about 10-20 min. Most of the compounds displayed IC50 values higher than 400 mu M. Compounds 5 (trans-3-(p-methoxy) benzyl-4-methyl-3-methoxycarbonyl-gamma-butyrolactone) and 10 (trans-3-(pmethoxy) benzyl-4-benzyl-3-methoxycarbonyl-gamma-butyrolactone) were the exceptions: they displayed IC50 values of 170.4 and 179.6 M, respectively, suggesting that the leishmanicidal activity of 3-methoxycarbonyl-gamma-butyrolactones may be related to the nature and size of the substituent at position C-4.