Ciguatoxin, allylations

C-Allylation has also been used in the construction of the BCD ring system of ciguatoxin [248]. Finally, the anomeric allylation reaction works equally well with ketose glycosides to yield bis substituted C-glycosyl derivatives, which were used in the total synthesis of (+)-citreoviral [249]. 

Cyclic ethers also serve as excellent ligands for chelation-controlled reactions, and this technique is especially useful for the synthesis of carbohydrate derivatives and polyether antibiotics. Studies toward ciguatoxin (Scheme 5.2.18) illustrate the oxidative cleavage of alkene 73 to provide the a-alkoxy aldehyde 74 for subsequent chelation-controlled allylation to yield 75.29... 

A similar problem was encountered in the synthesis of okadaic acid, which contains a number of allylic ethers. In this case, successful debenzylation was achieved using LiDBB in THF (70% yield), but in the case of a ciguatoxin synthesis, LiDBB did cleave an allylic ether. In this case, Na/NH3,EtOH, THF, 90°C, 10 min resulted in successful deprotection albeit in only 30-40% yield. ... 

The removal of benzyl ethers in the presence of allylic ethers can be a problem, as illustrated in the synthesis of Ciguatoxin. This method was found to prevent TIPS migration that occurred while attempting to remove a benzyl group with a variety of Lewis acids. 

DDQ, CH2CI2, H2O, rt 24 h, 58-80% yield. - Allylic ethers such as those in Ciguatoxin CTX3C, which are sometimes oxidized with DDQ, survived. In the presence of an adjacent hydroxyl the acetal can form as a by-product. This is the only product when using pure acetonitrile as the solvent. ... 

Clark, J.S., Hamelin, O., and Hufton, R. (1998) Synthesis of mediumsized cyclic allylic ethers by ring-dosing metathesis and subsequent elaboration to sub-units found in the brevetoxins and ciguatoxins. 

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