Synthesis of the macrocyclic spermidine alkaloid (±)-(2R*,3R*)-3-hydroxycelacinnine

Article abstract of DOI:10.1002/1522-2675(20010613)84:6<1253::AID-HLCA1253>3.0.CO;2-U

The macrocyclic lactam alkaloid (±)-(2R*,3R*)-3-hydroxycelacinnine (1) derived from spermidine was synthesized via stereoselective epoxide-ring opening with magnesium azide and cesium carbonate promoted macrocyclization of the ditosylated diamino precursor 12 with 1,4-dibromobutane in the two key steps (Scheme 2). ¹H- and ¹³C-NMR Signal assignments from COSY, HSQC, and HMBC 2D NMR data of the synthesized 1 were compared with the earlier-described data of the natural 3-hydroxycelacinnine. The similarity of their ¹³C-NMR spectra point to the correctness of the proposed constitutional formula for natural 3-hydroxycelacinnine; however, different ¹H-NMR chemical shifts and coupling constants (J(2,3) = 9.0 vs. 1.2 Hz, resp.) in the α-hydroxy-β-amino lactam moiety suggest that natural 3-hydroxycelacinnine is the 2,3-cis-epimer of one synthetic (±)-1.