Asymmetric syntheses of the stereotetrads of Amphotericin B and Calyculin C
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en
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55, [26]
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Organic chemistry report, 3/2004
Abstract
Calyculin C and Amphotericin B are biologically active natural products. Amphotericin B is an antifungal agent, which has been a widely used drug in antifungal chemotherapy. Calyculin C is a potent protein phosphatase inhibitor and plays an important role in cancer research. Calyculin C and Amphotericin B contain a stereotetrad fragment. The synthesis of the syn, anti, anti stereotetrad of Amphotericin B was based on the thiopyranone ring and a chiral auxiliary strategies. The synthesis began with the introduction of the asymmetry into the thiopyranone ring via a tartrate derived chiral ortho ester, followed by a highly diastereoselective Mukaiyama aldol reaction and 1,3-syn diol reduction. The synthesis was complete in only six steps with reasonable yield and diastereoselectivity. The all-anti stereotetrad of Calyculin C was first approached through a convergent strategy but it yielded a wrong diastereomer as the major product. The linear synthesis began with a chiral boron crotylation followed by ozonolysis. The second crotylation with (Z)-crotyl trifluorosilane produced the desired anti, anti, anti stereochemistry with high diastereoselectivity.Description
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- Karisalmi K., Koskinen A. M. P., Nissinen M. and Rissanen K., 2003. Model studies on a diastereoselective synthesis of the C(33)-C(37) fragment of Amphotericin B. Tetrahedron 59, number 9, pages 1421-1427. [article1.pdf] © 2003 Elsevier Science. By permission.
- Karisalmi K., Rissanen K. and Koskinen A. M. P., 2003. An enantioselective synthesis of the C(33)-C(37) fragment of Amphotericin B. Organic & Biomolecular Chemistry 1, number 18, pages 3193-3196.
- Karisalmi K. and Koskinen A. M. P., 2004. Studies towards the synthesis of the C(9)-C(20) lactone-dipropionate fragment of Calyculin C. Synthesis 2004, number 9, pages 1331-1341.
- Karisalmi K. and Koskinen A. M. P., 2004. Stereoselective synthesis of the C<sub>9</sub>-C<sub>19</sub> lactone-dipropionate fragment of calyculin C. Tetrahedron Letters 45, in press. [article4.pdf] © 2004 Elsevier Science. By permission.