Multiple reactivities of dithranol towards 1-alkynyl Fischer carbene complexes (CO)5MC(OEt)CCPh (M = Cr, W) – Efficient chemical synthesis of aromatic polyketides

Reactions of anti-psoriasis drug dithranol with 1-alkynyl Fischer carbene complexes (CO)5MC(OEt)CCPh (M = Cr, W) were investigated under controlled conditions in which triethylamine-promoted C-addition, O-addition, electrophilic aromatic substitution, and cyclization consecutively occurred at up to five positions of dithranol. A remarkable solvent effect led to selective formation of polyphenolic organic and organometallic mono- and triscarbene complexes which were efficiently demetalated to the potentially bioactive aromatic polyketides with pyridine-N-oxide. All the organic and organometallic products were characterized by methods including X-ray single crystal structural determinations. These results have revealed the novel multiple reactivities of dithranol which might be associated to its clinical side effect, providing a new synthetic methodology to functionalize dithranol for medical purposes, and chemically synthesize aromatic polyketides.

Graphical abstractMultiple reactivities of dithranol were unveiled in its reactions with 1-alkynyl Fischer carbene complexes (CO)5MC(OEt)CCPh (M = Cr, W) under controlled conditions, directing formation of polyphenolic organic and/or organometallic mono- and triscarbene complexes.Figure optionsDownload full-size imageDownload as PowerPoint slide