Total synthesis of antitumor Goniothalamus styryllactones

Synthesis of eight enantiopure styryllactones has been achieved from a comm on precursor : ethyl (2S, 3S, 4R) -4-(t-butyldimethylsilyloxy) -2,3-isoprop ylidenedioxy -4-phenylbutanoate 16, prepared in five steps and 65 % yield f rom (R)-mandelic acid. Key elements for the synthesis of goniofufurone 3, g oniopypyrone 4, goniobutenolides A and B (5, 6) and 7-epi-goniofufurone 7 w ere the introduction of the Z-acrylate moiety by a Julia coupling between 1 6 or its epimer in benzylic position and methyl 3-phenylsulfonyl orthopropi onate 11 followed by a highly diastereoselective reduction of the resulting beta-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 reac tion. Goniodiol 1 and 9-deoxygoniopypyrone 2 were synthesized via an effici ent coupling between the primary triflate derived from the common intermedi ate 16 or its epimer and Ghosez's sulfone 11 followed by lactonization and PhSO2H elimination. Goniodiol 1 has been efficiently converted to another s tyryllactone : isogoniothalamin epoxide 41. Addition of the Ghosez's sulfon e to an epoxide derived from the enantiomer of 16 allowed a short synthesis of 8-epi-9-deoxygoniopypyrone 8, thereby establishing that its structure i s the following : (1R, 5R, 7S, 8S) -8-hydroxy-7-phenyl-2,6-dioxabicyclo[3.3 .1] nonan-3-one. (C) 1999 Elsevier Science Ltd. All rights reserved.