Total synthesis of securinega alkaloids (−)-norsecurinine, (−)-niruroidine and (−)-flueggine A

Abstract

A consecutive synthetic strategy was developed toward the total synthesis of securinega alkaloids. (-)-Norsecurinine was concisely assembled by addition of a methoxyallene to a ketone for efficient side-chain installation. Ring-closing metathesis was also utilized as a key step. The first total synthesis of (-)-niruroidine was achieved from (-)-norsecurinine in three steps, while the route to (-)-flueggine A featured a 1,3-dipolar cycloaddition to forge the core structure.

An Accelerated Intermolecular Rauhut–Currier Reaction Enables the Total Synthesis of (−)-Flueggenine C

“…To our pleasure, a nice balance between the reactivity and the product selectivity was achieved when TBAF was applied as a base and we could obtain dimer 23 in 60% yield as a single diastereomer (Table 1, entry 3). However, neither 22 18 nor 1 10 showed any noticeable reactivity (Table 1, entries 4 and 5). The TBAF-mediated RC reaction was also attempted to lactone 22 and norsecurinine (1).…”

“…10,23 While the direct γ-hydroxylation of enone 25 remained elusive, DMDO oxidation of silyl enol ether 30 afforded γ-hydroxylated enone derivative 31 as a single diastereomer. Our optimized synthetic route commenced with the reported enone 25 which could be accessed in five steps from commercially available Boc protected Dproline (Scheme 4).…”

“…1,10 Ye and coworkers showed that virosecurinine undergoes a [2+2]-photodimerization to yield flueggedine (2) in 5 % yield in 2013. 1,10 Ye and coworkers showed that virosecurinine undergoes a [2+2]-photodimerization to yield flueggedine (2) in 5 % yield in 2013.…”

Bio‐inspired Total Synthesis of Twelve Securinega Alkaloids: Structural Reassignments of (+)‐Virosine B and (−)‐Episecurinol A

“…However, doubts still persist about the absolute configuration of some members of this alkaloid family, such as virosine B ( 8 ) and episecurinol A ( 10 ) . Both of these neosecurinanes are structurally very similar to the neonorsecurinanes niruroidine ( 7 ) and epibubbialine ( 9 ), which have only one carbon less in their A‐ring, but somewhat surprisingly exhibit inverse optical rotations (see Figure ) …”

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

“…226) [595], sculponeatin N [596], vitamin D derivatives [597], ryanodol (e.g. [598], shikimic acids and pinitol [599], carbasugars [600], madangamine D ( a later step forms a macrocyclic amine via RCM) [601], the kaurene core [602], various securinega alkaloids [603], a labyssomicin C derivative (e.g. 228 in a moderately diastereoselective RCM using a substrate featuring diastereotopic vinyl groups) [604], the crotogoudin ring system [605], tetrahydrocannabinol derivatives (e.g.…”