Synthesis studies on the Melodinus alkaloid meloscine

Abstract

The pentacyclic Melodinus alkaloid (±)-meloscine was synthesized in 19 chemical steps from 2-bromobenzaldehyde through a route featuring an allenyl azide cyclization cascade to deliver the core azabicyclo[3.3.0]octane substructure. Peripheral functionalization of this core included a Tollens-type aldol condensation to set the quaternary center at C(20) and a diastereoselective ring closing metathesis to forge the tetrahydropyridine ring.

A Divergent Synthetic Route to the Vallesamidine and Schizozygine Alkaloids: Total Synthesis of (+)‐Vallesamidine and (+)‐14,15‐Dehydrostrempeliopine

“…Manipulations to form the metathesis precursor 8 for the formation of ring D began with the chemoselective reduction of malonate 9 to the corresponding diol under optimised conditions (LiAlH 4 , room temperature, 15 min; Scheme ). A concise route to 8 , based on work by Feldman and Antoline, was to oxidise the diol to a dialdehyde, followed by a Wittig reaction to give dialkene 8 . However, degradation was observed during the oxidation, and no appropriate conditions could be found.…”

“…Retrosynthetically, access to both targets 1 and 6 would involve the formation of ring D by diastereoselective ring‐closing metathesis– of 8 to give a common intermediate 7 (Scheme ). The two C20 vinyl substituents would be derived from malonate 9 .…”

Synthesis of a Ribose‐Incorporating Medium Ring Scaffold via a Challenging Ring‐Closing Metathesis Reaction

“…Consistent with this hypothesis, Cusson et al recently reported the formation of a nine‐membered lactone by RCM reaction which was highly dependent on the configuration of one of three of the stereocentres in the substrate . Other examples of diastereoselective RCM reactions have been reported for five‐ and six‐membered ring formations , . Interestingly, there appear to be subtle differences between the tri‐TBDPS‐protected and tri‐TBDMS‐protected substrates that allows medium ring formation of both epimers for the former, possibly simply due to increased protecting group size.…”

“…[24] Other examples of diastereoselective RCM reactions have been reported for fiveand six-membered ring formations. [25,26] Interestingly, there appear to be subtle differences between the tri-TBDPS-protected and tri-TBDMS-protected substrates that allows medium ring formation of both epimers for the former, possibly simply due to increased protecting group size.…”

The Genus Melodinus (Apocynaceae): Chemical and Pharmacological Perspectives

“…Substances are separated with liquid chromatography using different solvent mixtures with silica gel [13], charcoal [17] and sephadex [14] [18]. Other types of analytical techniques include thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) [19]- [22].…”