First Total Synthesis of Dermocanarin 2

Abstract

Dermocanarin 2 (2) is a naturally occurring pigment, in which an anthraquinone and a naphthoquinone are directly connected through a sigma bond and bridged by nine–membered lactone structure. Hindered rotation of the Csp²–Csp²bond between the quinone moieties renders axial chirality, and a stereogenic center exists in the lactone portion. Construction of the unique hexacyclic framework and rigorous control of absolute and relative stereochemistry make this compound a challenging synthetic target.

In this presentation, we report the first total synthesis of dermocanarin 2 (2). Key steps of the synthesis include (1) desymmetrization of s-symmetric biphenyl diacetate 11 by means of enzyme to afford axially chiral biphenyl 10 in an enantiomerically pure form (Scheme 2); (2) highly diastereoselective addition of ester enolate to the ketone moiety of biphenyl 9 to construct the C3’ stereogenic center (Table 1); (3) facile construction of the anthraquinone framework via the consecutive electrocyclization reactions of benzocyclobutene moiety under heating (Scheme 3, 22→23); (4) regioselective Diels–Alder reaction of the chlorobenzoquinone moiety in 25 with siloxy diene 6 to construct the naphthoquinone framework (Scheme 4, 25→26); (5) formation of the nine-membered lactone from the non-protected precursor 4, leading to the finish of the total synthesis (Scheme 4, 4→2).