Concise synthesis of the C15-C25 fragment of Thuggacins A-C

Mycobacterium tuberculosis is the obligate human respiratory system responsible for lethally contagious tuberculosis. The polyketide antibiotics Thuggacins A-C possessed potent, vigorous anti-tuberculosis activity against Mycobacterium tuberculosis with a different anti-tuberculosis mechanism targeting and inhibiting the bacterial respiratory chain. Herein, we report a novel and efficient route to construct the C15-C25 fragment of Thuggacins in 15 linear steps with 5.5 % overall yield using commercially available D-(+)-glucono-1,5-lactone as a chiral template. The key steps of this synthesis included substrate-controlled methylation, Weinreb ketone formation, Mitsunobu elimination and, the LiAlH4-assisted stereoselective reduction to prepare the contiguous stereogenic centers and the E, E-conjugated diene of Thuggacins A-C.