Asimicin synthesis

Thus, 1.7-octadiene (79), which was subjected to monohydroboration followed by asymmetric dihydroxylation of the remaining double bond to give triol 80 with approximately 80% ee. Further transformations then afforded the desired butenolide 81. Double asymmetric dihydroxylation of diene 83 and subsequent protection gave hydroxy lactone 84 [98], which was then converted into acetylenic bis(hydroxy)bistetrahydrofuran 82 as the required intermediate for the (+)-asimicin synthesis. Mitsunobu inversion at C-24 gave rise to the diastereomeric (+)-bullatacin precursor. 

The total synthesis of (+)-asimicin also uses this methodology for the introduction of the butenolide in one of the final steps, the formation of 117 from 116 (Scheme 15.34) [78], Owing to the small scale (18 pirn o 1), an excess of catalyst had to be used. 

In 1995, Hoye published total syntheses of (+)-asimicin (69) and (+)-bullatacin (70), which differ only in their configurations at C-24 [97J. Here, the AD was used for the synthesis of two key fragments, 81 and 82. 

A synthesis of the Annonaceous acetogenin asimicin and a side-chain analogue has been achieved by a highly convergent route in which Grubbs cross-metathesis played a key role.98... 

Scheme 10-25. Formal total synthesis of trilobacin and asimicin by Ruan and Mootoo.

The total synthesis of (+)-asimicin, which belongs to the family of Annonaceous acetogenins, was completed by E. Keinan and co-workers. In order to create one of the tetrahydrofuran rings stereospecifically, an intramolecular Williamson ether synthesis was performed between a secondary alcohol and a secondary mesylate using pyridine as the base. 

Isodeacetyl uvaricin 163 was isolated from Uvaria narum in 1991 (75), and more recently from Annona bullata and re-named 4-deoxy asimicin (76) In 1993, Sahpaz et al. (77) reported the hemi-synthesis of 163, starting from tripoxyrollin 164, which after treatment with perchloric acid (9) as already described in section 5.2., led to a complex mixture from which isodeacetyl uvaricin 163 could be characterized as well as other minor unnatural acetogenins (Fig. 28). 

Applications of cyclocarbonylation to the preparation of natural products include the synthesis of ( )-aristolactone [12], (+ )-hamabiwa]actone B [13], (+ )-asimicin, and (+ )-bullatadn [14], all of which involve 4-hydroxybutenolide motifs (Scheme 2.4). 

Carbonylation of alkenyl iodides according to the above protocol was applied by Hoye and co-workers to the total synthesis of naturally occurring butenohdcs. An example from the synthesis of (+)-asimicin and (+)-bullacitin is shown in Scheme 4. 

In the key step to completing asimicin, Roush and Tinsley used their [3+2]-cycloaddition to combine allylsilane 140 and tetrahydrofuran 141 (Scheme 37). The reaction was promoted by SnCla and resulted in bis-tetrahydrofuran 142 in 80 % yield as essentially a single diastereomer. Following protecting group and oxidation state modification, the synthesis of asimicin was completed using Trost s two-step approach to butenolides. 

In the synthesis of asimicin 75, which is a cytotoxic and pesticidal acetogenin from the Asimina triloba (Annona-ceae), two successive CM reactions with terminal olefins were efficiently used by Marshall and Sabatini (Scheme 24.19). The CM reaction of C2-symmetiric bis-alkene 70... 

Marshall JA, Sabatini JJ. An outside-in approach to adjacent bistetrahydrofuran annonaceous acetogenins with C2 core symmetry. Total synthesis of asimicin and a C32 analogue. Org. Lett. 2006 8 3557-3560. 

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