Total Synthesis of Salimabromide: A Tetracyclic Polyketide from a Marine Myxobacterium

Salimabromide
is an antibiotic polyketide that was previously isolated
from the obligate marine myxobacterium Enhygromyxa
salina, and its densely functionalized and conformationally
rigid tetracyclic framework is unprecedented in nature. Herein we
report the first chemical synthesis of the target structure by employing
a series of well-orchestrated, robust transformations, highlighted
by an acid-promoted, powerful Wagner–Meerwein rearrangement/Friedel–Crafts
cyclization sequence to forge the two adjacent quaternary carbon centers
embedded in the tetrahydronaphthalene. A high-yielding ketiminium
mediated [2+2]-cycloaddition was also utilized for the simultaneous
construction of the remaining three stereocenters.