Total Synthesis of Anti-tuberculosis Natural Products Ilamycins E₁ and F

The first total synthesis of the potent anti-tuberculosis cyclopeptide natural products ilamycins E 1 and F was achieved. This highly convergent strategy consists of the synthesis of the two units 10 and 11 and linking them together to form the macrocyclic lactam 31. The upper unit 10 was prepared from tryptophan in five steps, and the lower unit 11 was prepared from glutamic acid in thirteen steps. Conversion of ilamycin F, the most abundant of the cyclopeptides, into the more active congener, ilamycin E 1 , was also accomplished. This would provide sufficient material of ilamycin E 1 for more extensive biological studies.