<jats:title>Abstract</jats:title><jats:p>Wailupemycins H (<jats:bold>1</jats:bold>) and I (<jats:bold>2</jats:bold>) with a new skeleton coupled two 6-(2-phenylnaphthalene-1-yl)pyrane-2-one nuclei to a –CH<jats:sub>2</jats:sub>– linkage were identified from the culture of <jats:italic>Streptomyces</jats:italic> sp. OUCMDZ-3434 associated with the marine algae, <jats:italic>Enteromorpha prolifera</jats:italic>. Compounds <jats:bold>1</jats:bold> and <jats:bold>2</jats:bold> are two new α-glucosidase inhibitors with the K<jats:sub>i</jats:sub>/IC<jats:sub>50</jats:sub> values of 16.8/19.7 and 6.0/8.3 μM, respectively. In addition, the absolute configurations of wailupemycins D (<jats:bold>3</jats:bold>) and E (<jats:bold>4</jats:bold>) are also resolved in this paper for the first time.