Total Synthesis of the Annonaceous Acetogenins Asiminocin and Asiminecin by a Bidirectional Approach

A total synthesis of the Annonaceous acetogenins asiminocin and asiminecin is described. The approach is bidirectional starting from the ( S, S )-tartrate derived dialdehyde 7 and the ( R )-α-OSEM stannane 6 . Addition of 6 to 7 in the presence of InCl 3 afforded the bis-adduct, anti -diol 8 . The derived tosylate 9 was converted to the bis-tetrahydrofuran core unit 10 upon treatment with TBAF. Selective silylation of one of the two equivalent terminal diol groupings led to the OTBS ether alcohol 11 . Oxidation to aldehyde 12 and then InCl 3 -promoted addition of the ( S )-allylic stannane 14 gave the anti adduct 15 . Removal of the OH group by reduction of the tosylate 16 with LiBEt 3 H yielded the SEM ether 17 . Hydrogenation of the three double bonds of 17 followed by cleavage of the terminal silyl ether and oxidation afforded aldehyde 20 . Conversion to the vinylic iodide 21 followed by Pd(0)-catalyzed coupling with the ( S )-alkynyl butenolide 24 gave the asiminocin derivative 25 . Selective hydrogenation of the enyne moiety with diimide and cleavage of the SEM protecting groups completed the synthesis of asiminocin ( 27 ). Asiminecin ( 41 ) was prepared starting from aldehyde 12 and the OTBS allylic stannane 28 . Addition of the latter to the former in the presence of InCl 3 afforded the anti adduct 29 which was protected as the SEM ether 30 . Hydrogenation followed by OTBS cleavage with TBAF and selective silylation of the primary alcohol with TBSCl and Et 3 N−DMAP led to the secondary alcohol 33 . Tosylation and hydrogenolysis with LiEt 3 BH removed the C30 OTs group affording the SEM ether 35 . The remaining steps were carried out along the lines described for asiminocin via the vinyl iodide 38 which was coupled with acetylenic butenolide 24 to afford enyne 39 . Selective reduction with diimide and SEM cleavage completed the synthesis.