Synthesis of the Macrocyclic Spermidine Alkaloid (±)‐(2R*,3R*)‐3‐Hydroxycelacinnine

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 .