Fujianmycin B

SNA-8073-B, an inhibitor of prolyl endopeptidase isolated from the broth filtrate of Streptomyces sp. SNA-8073, is a new isotetracenone antibiotic. It was purified by ethyl acetate extraction, silica gel column chromatography and high performance liquid chromatography on ODS column. SNA-8073-B has the molecular formula of C20H16O5 and is a stereoisomer of SNA-8073-A (fujianmycin B, rubiginone A2). SNA-8073-B inhibited prolyl endopeptidase of Flavobacterium non-competitively (IC50 = 8.9 microM) when Z-Gly-Pro-pNA was used as a substrate, but SNA-8073-A did not show any inhibition even at 60 microM.

Convergent enantioselective syntheses of angucyclinone-type natural products rubiginones A(2) (2) and C(2) (1) and their 11-methoxy regioisomers 3 a and 3 b have been achieved by using two domino processes from a common enantiomerically pure 1-vinylcyclohexene 4. Key steps in the synthesis of this diene were the stereoselective conjugate addition of AlMe(3) on (SS)-[(p-tolylsulfinyl)methyl]-p-quinol (9) and the elimination of the beta-hydroxy sulfoxide fragment, after oxidation to sulfone, to recover a carbonyl group. The first domino sequence comprised Diels-Alder reaction with a sulfinyl naphthoquinone followed by sulfoxide elimination. An efficient opposite regioselection in the cycloaddition step was achieved in the convergent construction of the tetracyclic skeleton using a sulfoxide at C-2 or C-3 of the dienophiles 5 or 6, derived from 5-methoxy-1,4-naphthoquinone. The second domino process, triggered by oxygen and sunlight, allowed the transformation of the initial tetracyclic adducts into the final products after B ring aromatization, silyl deprotection and C-1 oxidation.

Four prolyl endopeptidase inhibitors isolated from actinomycetes, named propeptin, SNA-8073-B, staurosporine, and enduracidin were classified into 3 groups on the basis of their inhibition potency against prolyl endopeptidase from a bacterium (Flavobacterium) and a mammal (human placenta). Staurosporine inhibited the enzyme from Flavobacterium more strongly than that from human placenta. Enduracidin inhibited the enzyme from human placenta more strongly than that from Flavobacterium. Propeptin and SNA-8073-B, both new compounds, inhibited the enzymes from both origins to the same extent.