Concise Synthesis of Tunicamycin V and Discovery of a Cytostatic DPAGT1 Inhibitor

A short total synthesis of tunicamycin V (1), a non-selective phosphotransferase inhibitor, is achieved via Büchner–Curtius–Schlotterbeck type reaction. Tunicamycin can be synthesized in 15 chemical steps from D-galactal with 21 % overall yield. The established synthetic scheme operationally very simple and flexible to introduce building blocks interest. inhibitory activity one the designed analogues 28 against human dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 (DPAGT1) 12.5 times greater than 1. While tunicamycins are cytotoxic molecules low selectivity, novel analogue displays selective cytostatic breast cancer cell lines including triple-negative cancer.