1242597-66-5Relevant academic research and scientific papers
Total syntheses of arylindolizidine alkaloids (+)-ipalbidine and (+)-antofine
Niphakis, Micah J.,Georg, Gunda I.
supporting information; experimental part, p. 6019 - 6022 (2010/12/19)
This paper presents the first application of two recently developed reactions to natural product synthesis. The first method involves a 6-endo-trig cyclization to prepare a versatile chiral enaminone building block. The second is a direct C-H arylation reaction. As a showcase for the utility of these methods, (+)-antofine and (+)-ipalbidine were synthesized in only 8 steps and 24-26% overall yields.
Synthesis of 6- and 7-membered cyclic enaminones: Scope and mechanism
Niphakis, Micah J.,Turunen, Brandon J.,Georg, Gunda I.
supporting information; experimental part, p. 6793 - 6805 (2010/12/20)
Six- and seven-membered cyclic enaminones can be prepared using common, environmentally benign reagents. Amino acids are used as synthetic precursors allowing diversification and the incorporation of chirality. The key reaction in this multistep process involves deprotection of Boc-amino ynones and subsequent treatment with methanolic K2CO3 to induce cyclization. A β-amino elimination side reaction was identified in a few labile substrates that led to either loss of stereochemical purity or degradation. This process can be mitigated in specific cases using mild deprotection conditions. NMR and deuterium-labeling experiments provided valuable insight into the workings and limitations of this reaction. Although disguised as a 6-endo-dig cyclization, the reagents employed in the transformation play a direct role in bond-making and bond-breaking, thus changing the mode of addition to a 6-endo-trig cyclization. This method can be used to construct an array of monocyclic and bicyclic scaffolds, many of which are found in well-known natural products (e.g., indolizidine, quinolizidine, and Stemona alkaloids).
