Synthetic studies towards hamigeromycins A, B and E and total synthesis of 5'-epi-caryospomycin C and hyalodendriellin A.

Synthetic studies towards naturally occurring resorcylic acid lactones (RALs) hamigeromycins A, B and E are disclosed in this article. The synthetic strategy involves a late-stage intramolecular macrolactonization protocol through a transesterification reaction. The stereocenters (C4' and C5') present in both hamigeromycins A and E were accessed through chiral pool starting materials (D- and L-arabinose). Though the total synthesis of hamigeromycins A, B and E remains elusive, we have completed the total synthesis of structurally related hyalodendriellein A and 5'-epi-caryospomycin C for the first time. The penta-substituted aromatic core present in the target natural products was accessed by using 2,4,5-trimethoxybenzoic acid as a precursor. The crucial E-olefinic unsaturation at C1'-C2' was constructed with a stereoselective decarboxylative Heck reaction.