Muironolide A, a new chemical entity with an unprecedented chlorinated hexahydro-1H-isoindolone skeleton, was isolated in only 90 microg yield from the same marine sponge, Phorbas sp. that also provided phorboxazoles A and B. The structure was solved by interpretation of NMR data obtained at 600 MHz with a 1.7 mm cryo-microprobe in combination with FTMS, exciton coupled CD, and stereochemical correlation with authentic standards prepared by Reformatsky reaction of (-)-(1R,2S)-2-chloro-1-cyclopropanecarboxaldehyde. The absolute configuration of the chlorocyclopropane ring in 1 is opposite to that of co-occurring phorbasides A-F. Muironolide A is the first described macrolide bearing an esterified trichloromethyl carbinol, and may be produced by a cyanobacterium that also makes phorbasides.