Kuwahara Shigefumi

The 2 H ‐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‐4 H ‐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−CaCl 2 ‐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.

Enantioselective total synthesis of the aglycone of burnettramic acid A, an antifungal pyrrolizidinedione with a terminally mannosylated long acyl chain produced by Aspergillus fungi, has been achieved from a known carboxylic acid by a 14-step sequence. The key steps include 2 types of asymmetric alkylation, coupling of an acetylide intermediate with (S)-epichlorohydrin to provide an acetylenic epoxide in 1 pot, and the Birch reduction to effect desulfonylation, semi-reduction of triple bond, and debenzylation in a concurrent manner. Good agreement of the synthetic aglycone with naturally occurring one in 1H and 13C nuclear magnetic resonance (NMR) spectra, coupled with previously reported unambiguous stereochemical assignment of the sugar moiety, has confirmed the structure of burnettramic acid A.