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

✍ Scribed by Nikolai A. Khanjin; Manfred Hesse

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: German
• Weight: 413 KB
• Volume: 86
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200390160

✦ Synopsis

Abstract

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