The semisynthetic process initially described for the synthesis of 1 (ET-743) has been extended to the preparation of other natural ecteinascidins. For the synthesis of 2 (ET-729) a demethylation of a N-Me intermediate was carried out by a selective oxidation with MCPBA. Other natural ecteinascidins (ET-745, ET-759B, ET-736, ET-637, ET-594) were accessible from key intermediate 25. The described methodologies allow for the preparation of a wide variety of ecteinascidins by procedures that can be easily scaled up.
The all diastereomeric stereotetrads (polypropionate fragments) were synthesized in a stereodivergent fashion, starting from the Diels-Alder adducts of furan with acrylic acid and (-)-2-camphanoxyacrylonitrile, respectively. The key intermediates of these sequences were the oxanorbornenic sulfones 7, (-)-53 and (+)-54. Regio- and stereocontrolled alkylative ring opening of these intermediates afforded the cyclohexenyl sulfones 14, (+)-55 and (-)-58 which were transformed into the desired stereotetrads 30, 31, 40, 41, (+)-62, (+)-63, (-)-66, and (+)-69.
[figure: see text] The synthesis of the cyclohexan subunit of the siphonarlid metabolites baconipyrones A and B from furan is described. A key step included the alkylative ring opening of 7-oxanorbornenic sulfone 4 and oxidative desulfonylation of compound 8.
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