Two Synthesis Approaches of the 2H-Tetrahydro-4,6-dioxo-1,2-oxazine Ring System of Alchivemycins A and B

The 2H-tetrahydro-4,6-dioxo-1,2-oxazine (TDO) ring, a rare structural motif embedded in the molecular architecture of alchivemycins, is synthesized from 2,2,6-trimethyl-4H-1,3-dioxin-4-one via two routes. Both routes involve the intramolecular trapping of an acylketene intermediate by an internal hydroxy group to form the TDO ring as a key step. The first synthesis was achieved in 29 % overall yield from the starting material by a four-step sequence featuring a DMAP-CaCl2-mediated O- to C-acyl migration reaction to install an acyl group at the C5 position of the TDO ring. The second synthesis was completed in 8 % overall yield from the same starting material as the first one through five steps by exploiting a photo-induced double bromination reaction.