Twenty-eight natural and unnatural lamellarins with either a saturated or an unsaturated D-ring were synthesized according to our developed synthetic route. The key step involved the Michael addition/ring closure (Mi-RC) of the benzyldihydroisoquinoline and alpha-nitrocinnamate derivatives, which provided the 2-carboethoxypyrrole intermediates in moderate to good yields (up to 78% yield). Subsequent hydrogenolysis/lactonization furnished lamellarins with a saturated D-ring in excellent yields (up to 93% yield). DDQ oxidation of the saturated lamellarin acetates led directly to the corresponding unsaturated analogues in 54-95% yield. In addition, only two steps in our developed strategy require column chromatography.

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Alkaloid achievement: Lamellarins, a new class of potential nontoxic inhibitors of HIV‐1 integrase that are also responsible for multidrug‐resistance reversal in cancer cell lines, could be synthesized in three chemical steps and in 60 % overall yields from two simple starting materials (see scheme). The key step in the convergent synthetic approach involved the novel Michael addition/ring‐closure reaction to give the pyrrole core and the ester group required for subsequent lactonization in one step.