Total Synthesis of Pulchellalactam

Pulchellalactam is a natural product isolated from the fungus Collospora pulchella with anticancer potential.1 Although there are several routes reported for this compound, its total synthesis is still a challenge.2 In this work, we proposed the synthesis of lactone 3a as key step to reach the Pulchellalactam. First step involved the hydroiodination of but-2-ynoic (1) acid to afford 2 in 83% yield.3 Then, 3a was accomplished by tandem Sonogashira cross-coupling lactonization between 2 and 3-methyl-butyne.4-6 Optimization conditions of this step resulted in develop for a new methodology that afford compound 3a in 67% yield. To determinate the scope of this optimization, analogues 3b-d were synthetized in yields between 63% and 45% The final step involved an aminolysis of lactone 3a yielding the natural product in 89%. This new synthetic route afforded the Pulchellalactam stereoselectively, in three steps and with an overall yield of 48 %.