Total Synthesis of (±)-Phomactin G, a Platelet Activating Factor Antagonist from the Marine Fungus Phoma sp.

A total synthesis of phomactin G (3), which is a central intermediate in the biosynthesis of phomactin A (5) in Phoma sp. is described. The synthesis is based on a Cr(II)/Ni(II) macrocyclisation from the aldehyde vinyl iodide 9, leading to 16, followed by sequential conversion of 16 into the -epoxide 21 and the ketone 25 which, on deprotection, led to (±)-phomactin G. Phomactin G (3) shares an interesting structural homology with phomactin D (2), the most potent PAF-antagonist metabolite in Phoma sp. It is most likely converted into phomactin A (5), by initial allylic oxidation to the transient -alcohol phomactin structure 4, known as Sch 49028, followed by spontaneous pyran ring formation.

A total synthesis of (+/-)-phomactin A

A total synthesis of the PAF antagonist phomactin A (1), isolated from the marine fungus Phoma sp. is described. The synthesis is based on a Cr(II)/Ni(II) macrocyclisation from the aldehyde vinyl iodide 14, leading to the key phomactatrienol intermediate 16a, followed by elaboration of 16a to the epoxyketone 21, which undergoes spontaneous pyran and hemiacetal ring formation to 1 on deprotection with DDQ.