Lactonamycin is a natural antibiotic that exhibits potent antimicrobial and anticancer activities. It has a
unique hexacyclic aglycone core (lactonamycinone) that features with a naphtho[e]isoindole moiety incorporating
a densely oxygenated fused perhydrofuran-furanone ring with a labile tertiary methoxy moiety, and a 2-deoxy
sugar unit attached by a tertiary -ketoglycosidic bond. The intriguing structure of the lactonamycin and the urgent
need for novel effective antibiotics against resistant bacterial infections have stimulated considerable efforts towards
the total synthesis of lactonamycin and its analogs. This paper summarizes the recent progresses towards the
total synthesis of lactonamycin and its analogs, including the construction of the AB, ABCD, ABCDE, EF, CDEF, BCDEF ring systems,
and the aglycone core.