Four new polyol polyketides containing a decalin ring, nahuoic acids B–E (1–4), together with a known analogue, nahuoic acid A (5), possessing an unprecedented carbon skeleton, were isolated from a culture broth of the marine-derived Streptomyces sp. SCSGAA 0027. Their structures were determined by detailed analysis of spectroscopic data and chemical transformations including acetonide formation and Mosher's ester method. Compounds 1–5 showed weak antibiofilm activity against Shewanella onedensis MR-1 biofilm. This is the first series of analogues of the novel selective SETD8 inhibitor nahuoic acid A.