Total Synthesis of Halipeptins: Isolation of Halipeptin D and Synthesis of Oxazoline Halipeptin Analogues.

The isolation from the marine sponge Leiosella cf. arenifibrosa and structural elucidation of halipeptin D (5), a relative of the previously isolated halipeptins A–C (1–3), is described along with the total synthesis of a number of oxazoline analogues (7 a–d and epi-7 c–d). The developed synthetic strategy provides a flexible entry into the various isomers of the polyketide domain of the halipeptins and improvises for a late stage construction of the oxazoline ring after a macrolactamization process which secures the required macrocycle.