An Enantioselective Synthesis of -Arisugacin

The level of enantiomeric excess [ee] for (7 )-89 was found to be in the range of 85-95% using H NMR ratios of corresponding diastereomeric naproxen esters. By comparing with optical rotation of the known ( 5j-89 [[oc]23d = - 53.0° (c 1.0, CHCI3)] with an ee 90% [confirmed by Mosher s esters],713 optical rotation of (7 )-89 [[0c]23d = + 53.2° (c 1.0, CHCI3)] also confirms its level of ee and absolute configuration at Cl. 

Dihydroxylation60 of (-)-82 in pyridine, a protocol used for our racemic synthesis was found to be difficult here mainly due to problems in the isolation of the tetraol product. We elected to go with the epoxidation protocol60 using various peroxy acetic acids, and the best result gave (-)-84 in 21% yield in addition to a hexacyclein 28% yield.63 64 

RPH thanks NIH [NS38049] and American Chemical Society Petroleum Research Fund [Type-G] for financial support, and the McKnight Foundation for a McKnight Fellowship. In addition to the co-author KPC for this chapter, RPH would like to thank 

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It is noteworthy that stereochemical control of the two new stereogenic centers at C4a and Cl2b ultimately stems from the stereochemistry at Cl through the intramolecular Diels-Alder reaction. Hence, an optically pure 46 should lead to an enantioselective preparation of a-epoxy lactone 48, thereby ultimately leading to an enantioselective synthesis of arisugacin A [1], LAH reduction of ( )-a-epoxy lactone 48 led to epoxy diol 49 in 78%... 

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