Oxidative Cleavage of the Carbon Framework

Carbon-carbon double bonds in oxabicydic systems are cleaved by ozonolysis. Moreover, tri-substituted olefins generate cyclic ethers bearing side chains with differentiated ends upon ozonolytic cleavage, thus allowing subsequent selective elaboration of each appendage. Naked sugars were used extensively by Vogel as furanosides and C-nucleoside derivatives [11a]. 

In addition to the studies in the [2.2.1] oxabicydic series, Vogel also subjected the [3.2.1] oxabicydic vinyl chloride 120 to ozonolysis to produce a dialkylated tetrahydropyran 121 with differentially oxidized substituents at C2 and C6, Eq. 89 [91]. This sequence of reactions was utilized in the synthesis of / -C-hexo-pyranosides such as 122. 

Bicyclic ether 124, obtained from the intramolecular cycloaddition of 123, was subjected to ozonolysis with a reductive work-up, Eq. 90. Silyl protection gave alcohol 125 and reduction transformed the thioether linkage into the vicinal cis dimethyl groups found in ( )-nemorensic acid [137]. 

Previous synthetic studies that have employed ozonolysis as a means for cleaving oxabicydic substrates include Meinwald s studies toward pederin [138], Just s synthesis of showdowmycin [139], Masamune s synthesis of avenaciolide [140], and Ohno s asymmetric syntheses of (+)-showdowmycin, (-)-cordycepin C, and (-)-6-azapseudouridine [141 a]. 

A key step in the recent synthesis of (+)-lauthisan by Cha was the ozonolytic cleavage of the olefinic bond of the tricyclic substrate 127 to afford the cyclic ether 128, Eq. 91 [115]. A series of transformations including an enzymatic desymmetrization completed the total synthesis. 

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