Asymmetric Syntheses of Nakinadine D, Nakinadine E, and Nakinadine F: Confirmation of Their Relative (RS,SR)‑Configurations and Proposal of Their Absolute (2S,3R)‑Configurations

The syn- and anti-diastereoisomeric forms of the reported structures of the marine alkaloids nakinadines D–F have been synthesized, for the first time in all cases, via an approach involving asymmetric Mannich-type (imino-aldol) reactions of methyl phenylacetate with N-tert-butylsulfinyl imines as the key steps to control the stereochemistry. Comparison of the 1H and 13C NMR spectroscopic data reported for the natural materials with those acquired for these synthetic samples confirms the initially assigned relative (RS,SR)-configurations of these three alkaloids. In the absence of specific rotation (or other diagnostic) data for the natural materials, it is not possible to unambiguously assign their absolute configurations, although given the absolute (2S)-configurations assigned to nakinadines B and C, and the absolute (2S,3R)-configuration previously established for nakinadine A, the data herein uphold our proposal that nakinadines D–F share the absolute (2S,3R)-configuration.