Synthesis of Bioactive Side‐Chain Analogues of TAN‐2483B |
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Authors: | Kalpani K Somarathne Jordan A J McCone Amira Brackovic Jos Luis Pinedo Rivera J Robin Fulton Euan Russell Jessica J Field Christopher L Orme Hedley L Stirrat Jasmin Riesterer Paul H Teesdale‐Spittle John H Miller Joanne E Harvey |
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Institution: | Kalpani K. Somarathne,Jordan A. J. McCone,Amira Brackovic,José Luis Pinedo Rivera,J. Robin Fulton,Euan Russell,Jessica J. Field,Christopher L. Orme,Hedley L. Stirrat,Jasmin Riesterer,Paul H. Teesdale‐Spittle,John H. Miller,Joanne E. Harvey |
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Abstract: | The fungal metabolite TAN‐2483B has a 2,6‐trans‐relationship across the pyran ring of its furo3,4‐b]pyran‐5‐one core, which has thwarted previous attempts at its synthesis. We have now developed a chiral pool approach to this core and prepared side‐chain analogues of TAN‐2483B. The synthesis relies on ring expansion of a reactive furan ring‐fused dibromocyclopropane and alkynylation of the resulting pyran. The furan ring is constructed by palladium‐catalysed carbonylative lactonisation. Various side‐chains are appended through Wittig‐type chemistry. The prepared analogues showed micromolar activity towards cancer cell lines HL‐60, 1A9 and MCF‐7 and certain human disease‐relevant kinases, including Bruton's tyrosine kinase (Btk). |
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Keywords: | cyclopropane ring expansion fungal metabolites furo[3 4-b]pyran-5-one palladium-catalyzed carbonylation TAN-2483B analog alpha-selective alkynylation |
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