An Enantioselective Organocatalytic Approach to Both Enantiomers of Lasubine II

Abstract

A concise stereoselective route providing access to both enantiomers of the bioactive quinolizidine alkaloid lasubine II has been developed. The enantioselectivity was introduced by taking advantage of a proline-catalyzed asymmetric Mannich reaction. Next, the bicyclic system was constructed via a diastereoselective Mannich cyclization and subsequent ring-closing metathesis as the key steps.

Emergence of single-molecular chirality from achiral reactants

“…1 H-NMR (300 MHz, CDCl 3 ): δ =7.47 (d, J =16.2 Hz, 1H), 7.13 (dd, J= 2.1, 8.3 Hz, 1H), 7.08 (d, J =2.0 Hz, 1H), 6.88 (d, J =8.3 Hz, 1H), 6.61 (d, J =16.1 Hz, 1H), 3.92 (s, 6H), 2.37 (s, 3H). 1 H-NMR data are consistent with those reported in literature 25 .…”

“…1 H-NMR (300 MHz, CDCl 3 ): δ =6.91–6.87 (m, 2H), 6.82–6.79 (m, 1H), 6.73–6.66 (m, 1H), 6.55–6.49 (m, 2H), 4.69 (q, J =6.5 Hz, 1H), 4.11 (br s, 1H), 3.85 (s, 6H), 3.70 (s, 3H), 2.89 (d, J =6.6 Hz, 2H), 2.11 (s, 3H). 1 H-NMR data are consistent with those reported in literature 25 .…”

“…In solution, it was found that 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is a suitable catalyst for the forward aza-Michael reaction 24 and at the same time also catalyses the retro reaction 25 (see Supplementary Fig. 1 ).…”

Synthesis of (±)‐Lasubine II Using N‐Methoxyamines

“…[1] Although no biological activityo fl asubine II (1)h as been reported to date, the Lythraceaea lkaloids have been shown to possess ar ange of biological activities. [3][4][5] Our research group has been engaged in ap rogram devoted to the efficient total synthesis of natural products by taking advantage of unique properties of hetero atom-hetero atom bonds. This widely distributed structure has received considerable attention from the syntheticc hemistst od emonstrate the utility of new methods.…”

“…This widely distributed structure has received considerable attention from the syntheticc hemistst od emonstrate the utility of new methods. [3][4][5] Our research group has been engaged in ap rogram devoted to the efficient total synthesis of natural products by taking advantage of unique properties of hetero atom-hetero atom bonds. [6] In this context, we envisioned the synthetic approach to (AE)-lasubine II (1), whosek ey step is the three-component allylation of N-methoxyamine 5 [7,8] (Scheme 1B).…”