Asymmetric Total Synthesis Enables Discovery of Antibacterial Activity of Siladenoserinols A and H.

Siladenoserinols A and H were found to show moderate inhibitory activity toward p53-Hdm2 interactions. Our total synthesis allowed us to further examine their bioactivities, which revealed that (i) siladenoserinols A and H were not cytotoxic against cancer cell lines and (ii) siladenoserinol A and its desulfamate analogue exhibited significant antibacterial activity against Gram-positive bacteria including MRSA. Our studies demonstrate that siladenoserinols are a promising new class of bactericidal Gram-positive antibiotics without hemolytic activity.