- Synthesis of the macrocyclic spermidine alkaloid (±)-(2R*,3R*)-3-hydroxycelacinnine
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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.
- Khanjin, Nikolai A.,Hesse, Manfred
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- Synthesis of the spermidine alkaloids (-)-(2R,3R)- and (-)-(2R,3S)-3-hydroxycelacinnine: Macrocyclization with oxirane-ring opening and inversion via cyclic sulfamidates
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The two epimers (-)-1a and (-)-1b of the macrocyclic lactama kaloid 3-hydroxycelacinnine with the (2R,3R) and (2R,3S) 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 (2R,3R)-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 NaNO2 led to (2R,3S)-macrocycles. The synthesized (-)-(2R,3S)-3-hydroxycelacinnine ((-)-1b) was identical to the natural alkaloid.
- Khanjin, Nikolai A.,Hesse, Manfred
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p. 2028 - 2057
(2007/10/03)
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