Oxabicycloheptanes and oxabicycloheptenes for the treatment of diabetes

A method of increasing the insulin sensitivity of a mammalian cell by contacting the cell with a protein phosphatase 2A (PP2A) inhibitor having the structure:

• wherein
• bond α is present or absent;
• R1 and R2 is each independently H, O− or OR9,
• where R9 is H, alkyl, alkenyl, alkynyl or aryl,
• or R1 and R2 together are ═O;
• R3 and R4 are each different, and each is OH, O−, OR9, OR10, O(CH2)1-6R9, SH, S−, SR9,
• where X is O, S, NR10, or N+R10R10,
• where each R10 is independently H, alkyl, alkenyl, alkynyl, aryl, substituted aryl where the substituent is other than chloro when R1 and R2 are ═O,
• —CH2CN, —CH2CO2R11, —CH2COR11, —NHR11 or —NH+(R11)2,
• wherein each R11 is independently alkyl, alkenyl or alkynyl, or H;
• R5 and R6 is each independently H, OH, or R5 and R6 taken together are ═O;
• R7 and R8 is each independently H, F, Cl, Br, SO2Ph, CO2CH3, or SR12,
• where R12 is H, alkyl, alkenyl, alkynyl or aryl;
• and
• each occurrence of alkyl, alkenyl, or alkynyl is branched or unbranched, unsubstituted or substituted,
• or a salt, enantiomer or zwitterion of the compound.

A method of treating Type 2 Diabetes in a subject afflicted with Type 2 Diabetes comprising administering to the subject a therapeutically effective amount of a protein phosphatase 2A inhibitor having the structure:

• wherein
• bond α is present or absent;
• R1 and R2 is each independently H, O− or OR9,
• where R9 is H, alkyl, alkenyl, alkynyl or aryl,
• or R1 and R2 together are ═O;
• R3 and R4 are each different, and each is OH, O−, OR9, OR10, O(CH2)1-6R9, SH, S−, SR9,
• where X is O, S, NR10, or N+R10R10,
• where each R10 is independently H, alkyl, alkenyl, alkynyl, aryl, substituted aryl where the substituent is other than chloro when R1 and R2 are ═O,
• —CH2CN, —CH2CO2R11, —CH2COR11, —NHR11 or —NH+(R11)2,
• wherein each R11 is independently alkyl, alkenyl or alkynyl, or H;
• R5 and R6 is each independently H, OH, or R5 and R6 taken together are ═O;
• R7 and R8 is each independently H, F, Cl, Br, SO2Ph, CO2CH3, or SR12,
• where R12 is H, alkyl, alkenyl, alkynyl or aryl;
• and
• each occurrence of alkyl, alkenyl, or alkynyl is branched or unbranched, unsubstituted or substituted,
• or a salt, enantiomer or zwitterion of the compound.