The synthesis of 3-hydroxymethylfuro[3,2-b]naphtho[2,3-d]furan-5,10-dione, a novel metabolite isolated from Crescentia cujete

The title natural product 1, which possesses a new ring skeleton, has been synthesised by a sequence in which the key steps involve a tandem intramolecular Diels-Alder/reverse Diels-Alder reaction sequence. Thus 3-(2-furyl)-1,4-dimethoxynaphthalen-2-ol was treated with ethyl 3-bromopropiolate, and without isolation, the resulting acetylenic ether was heated in the presence of 3,6-di(pyridin-2-yl)-1,2,4,5-tetrazine. Intramolecular addition of the pendant acetylenic chain to the furan ring followed by cycloaddition of the electron-deficient tetrazine and subsequent cycloreversion delivered ethyl 5,10-dimethoxyfuro[3,2-b]naphtho[2,3-d]furan-3-carboxylate, which has the ring system of the natural product. Functional group manipulation then provided 1.