Synthesis of the AB-Ring Pyranolactone Substructure of Granaticin A

A synthesis of the AB-ring substructure of granaticin A was developed. The pyranolactone moiety was stereoselectively accessed by Sharpless asymmetric dihydroxylation and subsequent oxa-Pictet-Spengler cyclization. The use of BF3 center dot OEt2 resulted in the formation of the cis pyranolactone, whereas the combination of BF3 center dot OEt2 with trifluoroacetic acid led to the trans isomer. The resulting hydroquinones were cleaved selectively by ozonolysis to dicarboxylic acids. An aryl Grignard reagent could be regioselectively added to unsymmetrical anhydrides. As an alternative strategy for the construction of the B-ring, a benzyne-furan cycloaddition could be established.