Enantioselective Synthesis of (+)-Providencin and Its Unexpected Regioisomer via a Biomimetic Norrish-Yang Cyclization from (-)-Bipinnatin E.

A biomimetic semisynthesis of the diterpenoid (+)-providencin ( 2 ) and the unexpected novel C14 regioisomer 3 was achieved by photoirradiation of the proposed biosynthetic cembranoid precursor (-)-bipinnatin E ( 1 ). The absolute configuration assignments of 1 and 2 by correlation were established by X-ray analysis. A combination of NOESY data and photochemical reaction results revealed that both C2 and C14 positions of the macrocycle (-)- 1 are suitable for hydrogen abstraction, thus affording an explanation to the mixture of cyclobutane photoproduct isomers obtained by a Norrish-Yang cyclization. These results also support the proposed biosynthetic hypothesis describing the genuine photochemical transformation of (-)- 1 into (+)- 2 , without refuting that both regioisomer products 2 / 3 might be artifacts of isolation.