Gingerol enantioselective synthesis

Based on the recent impressive progress made on asymmetric hydrolysis, the design and bio-transformation of the optically active ethyl 2,2-difluoro-3-hydroxyoctanoate 78 and synthesis of optically active fluorinated [6]-gingerol derivatives are reported [82]. The following criteria were used in the search for a practical route to chiral ethyl 2,2-difluoro-3-hydroxyoctanoate with a high -value (1) the search of an additive to enhance the enantioselectivity of asymmetric hydrolysis by lipases, and (2) the modification of ethyl 2,2-difluoro-... 

The (R)-enantiomer of (242) has also been prepared and used as a chiral auxiliary in an enantioselective aldol synthesis of (+)-(S )-gingerol (79CB3703). (R )-Glutamic acid (246) was thus converted into (i )-pyroglutamic acid by simply heating in water. Conversion of (247) to its methyl ester and LAH reduction delivered alcohol (248). Ethyl nitrite treatment of (248) gave nitrosoamine (249), which was methylated to furnish (250). Exposure of (250) to LAH completed the synthesis of the required chiral auxiliary RAMP [(R)- l-amino-2-(methoxymethyl)pyrrolidine]. The hydrazone (252), derived from RAMP and acetone, was... 

Chiral a-sulfinyl dimethylhydrazones form stabilized carbanions that can be used in enantioselective aldol reactions. A typical example is shown in equation (21). Removal of the chiral sulfur auxiliary is accomplished by reductive desulfurization. Under these conditions recovery and reuse of the sulfur moiety is impossible. Synthetic and optical yields reported for these aldol reactions are modest in most cases. However, in a direct comparison to the SAMpMaMP methodology, Annunziata has prepared (-)-(/ )-[6]-gingerol in 60% finders prior synthesis had yielded this aldol product in 36% ee. ... 

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