An enantioselective approach to the Securinega alkaloids: the total synthesis of (+)-norsecurinine and (+)-allonorsecurinine

Stereoselective Total Syntheses of (−)‐Flueggine A and (+)‐Virosaine B

“…[3] More recently, these alkaloids have been reported to exhibit important biological activities, including diuretic, hepatic protection, antimicrobial, antibacterial, and GABAA receptor and tagonism. Other naturally occurring Securinega alkaloids include (À)-norsecurinine (3), [7] (+)-allonorsecurinine (4), [8] securinine (5), [7] and flueggine B (6). Their structures and absolute configurations were elucidated by means of NMR spectroscopy, single-crystal X-ray diffraction, and circular dichroism (CD) analyses.…”

“…Following the biomimetic transformation proposed by Ye and workers, [6] we envisaged that (+)-virosaine B (2) could be formed by the intramolecular 1,3-dipolar cycloaddition from nitrone 10, which could in turn be prepared from (+)-allonorsecurinine (4), [8,14] through a process involving a [2,3]-Meisenheimer rearrangement [15] followed by a concerted [1,3]-sigmatropic rearrangement [16] (see also Schemes 4 and 5). It was envisaged that the construction of (+)-allonorsecurinine (4) could be achieved from d-proline (6) according to a similar process to that descried for the construction of (À)-norsecurinine (3) via the key intermediates 11 and 12 ( Figure 2).…”

“…[8] With (À)-norsecurinine (3) and (+)-allonorsecurinine (4) in hand, we proceeded toward our proposed total syntheses of (À)-flueggine A (1) and (+)-virosaine B (2). The physical properties of synthetic 4 were in good agreement with those reported for the natural material.…”

Stereoselective Total Syntheses of (−)‐Flueggine A and (+)‐Virosaine B

“…Their structures and absolute configurations were elucidated by means of NMR spectroscopy, single-crystal X-ray diffraction, and circular dichroism (CD) analyses. Other naturally occurring Securinega alkaloids include (À)-norsecurinine (3), [7] (+)-allonorsecurinine (4), [8] securinine (5), [7] and flueggine B (6). [5] Structurally, both flueggine A (1) and (+)-virosaine B (2) possess a unique structural framework based on their isoxazolidine and 7-oxa-1-azabicyclo[3.2.1]octane rings, which is unprecedented in the Securinega alkaloids.…”

“…Following the biomimetic transformation proposed by Ye and workers, [6] we envisaged that (+)-virosaine B (2) could be formed by the intramolecular 1,3-dipolar cycloaddition from nitrone 10, which could in turn be prepared from (+)-allonorsecurinine (4), [8,14] through a process involving a [2,3]-Meisenheimer rearrangement [15] followed by a concerted [1,3]-sigmatropic rearrangement [16] (see also Schemes 4 and 5). It was envisaged that the construction of (+)-allonorsecurinine (4) could be achieved from d-proline (6) according to a similar process to that descried for the construction of (À)-norsecurinine (3) via the key intermediates 11 and 12 ( Figure 2).…”