Total synthesis and antiproliferative/cytotoxic profiling of 2-epi-jaspine B

•The convergent total synthesis of 2-epi-jaspine B was developed.•The cornerstone of this strategy was the substrate-directed Overman rearrangement.•Chemical correlations of the key intermediates were performed.•The target 2-epi-jaspine B exhibited significant antiproliferative/cytotoxic activity.

A straightforward access to 2-epi-jaspine B (4.HCl) has been developed. Key to the approach was the use of Overman rearrangement for the instalment of a stereocentre bearing a nitrogen atom. Subsequent rational execution of the stereoselective transformations furnished the functionalized scaffold 38, whose coupling with a lipophilic segment under Wittig conditions, followed by deprotection and a THF core construction, completed the convergent synthesis of 2-epimer of 1. The final anhydrophytosphingosine 4.HCl was screened for its antiproliferative/cytotoxic activity employing multiple human cancer cell lines. In vitro evaluation revealed that 2-epi-jaspine B exhibited significant antitumour growth inhibitory activity against all used cells.

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