Penicimutans and aranorosins are a rich family of secondary metabolites produced by fungi of terrestrial and marine origin. These natural products contain polyketides, indole alkloids or both. The aranorosin-type polyketides feature an unusually hexa-functionalized cyclohexane core that contains an acid/base-sensitive cis-bisoxirane moiety, and is part of the 1-oxaspiro[4.5]decane ring skeleton. The penicimutan-type alkaloids contain a diketopiperazine-fused hexapyrroloindoline motif, which possesses a 1,1-dimethylpropenyl (reverse prenyl) group on the C3 carbon, generating the vicinal quaternary stereocenters. Both penicimutans and aranorosins display very promising biological activities against tumors and/or Gram-responsive microbial. Their drug lead potential attracted many synthetic efforts since 1990s. This review summarized all the synthetic studies until the February of 2021. © 2021 Elsevier Ltd