Total synthesis of (()-hyphodermin

Total synthesis of (()-hyphodermin B 1 was achieved from
diketone 5 in six steps and 15% overall yield. Notably, the
synthesis was developed without the need for complex protection-
deprotection strategies and exploited the unexpected
regioselective reduction of anhydride 3. The solid-state structure
of 1 is reported for the first time. Computer modeling studies
of 3 and X-ray crystallographic data for 1 provide supporting
evidence for the unexpected reactivity of C1 of anhydride 3 to
oxygen nucleophiles. With synthetic quantities of hyphodermin
B 1 now in hand, further investigations into the biological
activity of hyphodermin B 1 and its simple derivatives will be
carried out.