Synthesis of the Spermidine Alkaloids (−)‐(2R,3R)‐ and (−)‐(2R,3S)‐3‐Hydroxycelacinnine: Macrocyclization with Oxirane‐Ring Opening and Inversion via Cyclic Sulfamidates

摘要: The two epimers (−)-1a and (−)-1b of the macrocyclic lactam alkaloid 3-hydroxycelacinnine with (2R,3R) (2R,3S) absolute configurations, respectively, were synthesized by an alternative route involving macrocyclization regio- stereoselective oxirane-ring opening terminal amino group (Schemes 2 6). Properly N-protected chiral trans-oxirane precursors provided (2R,3R)-macrocycles after a one-pot deprotection-macrocyclization step under moderate dilution (0.005–0.01M). best yields (65–85%) achieved trifluoroacetyl protection. Macrocyclization corresponding cis-oxiranes was unsuccessful for steric reasons. Inversion at OHC(3) via nucleophilic displacement cyclic sulfamidate derivative NaNO2 led to (2R,3S)-macrocycles. (−)-(2R,3S)-3-hydroxycelacinnine ((−)-1b) identical natural alkaloid.