Synthetic studies towards naturally occurring macrolactams melearorides A and B: a chemo-enzymatic approach.

Synthetic efforts directed towards the asymmetric total synthesis of two naturally occurring fungal macrolactams, melearorides A and B, were disclosed in this article. The strategy involves a late-stage intramolecular macrolactonisation approach for constructing a 13-membered macrolactam framework. For both molecules, the crucial C7-C8 bond was constructed via a cross-metathesis (CM) reaction followed by hydrogenation. The stereocenters at C6 and C9 in melearoride A were constructed through a lipase-mediated enzymatic kinetic resolution (EKR) reaction. For melearoride B, stereocenters at C11 and C9 were constructed through an asymmetric Keck allylation and Jacobsen hydrolytic kinetic resolution (HKR) reaction.