Total synthesis of antitumor Goniothalamus styryllactones

Article abstract of DOI:10.1016/S0040-4020(99)00794-2

Synthesis of eight enantiopure styryllactones has been achieved from a common precursor: ethyl (2S, 3S, 4R)-4-(t-butyldimethylsilyloxy)-2,3- isopropylidenedioxy-4-phenylbutanoate 16, prepared in five steps and 65% yield from (R)-mandelic acid. Key elements for the synthesis of goniofufurone 3, goniopypyrone 4, goniobutenolides A and B (5, 6) and 7-epi-goniofufurone 7 were the introduction of the Z-acrylate moiety by a Julia coupling between 16 or its epimer in benzylic position and methyl 3-phenylsulfonyl orthopropionate 11 followed by a highly diastereoselective reduction of the resulting β-keto sulfone which sets up the last of the four contiguous asymmetric center. In the case of styryllactones 4 and 7, prior to the Julia coupling, the benzyl sterocenter of 16 was efficiently inverted by a Mitsunobu reaction. Goniodiol 1 and 9-deoxygoniopypyrone 2 were synthesized via an efficient coupling between the primary triflate derived from the common intermediate 16 or its epimer and Ghosez's sulfone 11 followed by lactonization and PhSO₂H elimination. Goniodiol 1 has been efficiently converted to another styryllactone: isogoniothalamin epoxide 41. Addition of the Ghosez's sulfone to an epoxide derived from the enantiomer of 16 allowed a short synthesis of 8-epi-9-deoxygoniopypyrone 8, thereby establishing that its structure is the following: (1R, 5R, 7S, 8S)-8-hydroxy-7-phenyl-2,6- dioxabicyclo[3.3.1] nonan-3-one.