Total Enantioselective Synthesis of (−)-Cytisine

Abstract

[reaction: see text] The first total enantiosynthesis of the biologically active alkaloid (-)-cytisine is reported, featuring a ruthenium-catalyzed RCM reaction as the key step. The approach relies on readily available cis-piperidine-3,5-dimethanol monoacetate as the chiral building block, and it is suited for achieving the target compound in both enantiomeric forms.

Stereodivergent Diversity‐Oriented Synthesis: Exploiting the Versatility of 2‐Piperidine Ethanol

“…It is noteworthy that compounds 8 presents the isomeric scaffold of some lupin alkaloids, such as cytisine, sparteine and anagyramide, [25][26][27][28] while products 9 are characterized by a simplified structure of several Lycopodium alkaloids, like lycocernuine and cernuine. It is noteworthy that compounds 8 presents the isomeric scaffold of some lupin alkaloids, such as cytisine, sparteine and anagyramide, [25][26][27][28] while products 9 are characterized by a simplified structure of several Lycopodium alkaloids, like lycocernuine and cernuine.…”

Synthesis of Pironetin–Dumetorine Hybrids as Tubulin Binders

“…[1][2][3][4][5] Given our interests in: a) the total synthesis of piperidine-based natural products, [6][7][8][9][10][11][12][13][14] b) the modification of natural products, [15][16][17][18][19][20][21][22][23][24][25][26] and c) the discovery and generation of new anticancer compounds, [27][28][29][30][31] we considered the natural product pironetin [32] due to its capacity for α-tubulin binding. [1][2][3][4][5] Given our interests in: a) the total synthesis of piperidine-based natural products, [6][7][8][9][10][11][12][13][14] b) the modification of natural products, [15][16][17]…”

The First Modular Route to Core‐Chiral Bispidine Ligands and Their Application in Enantioselective Copper(II)‐Catalyzed Henry Reactions

“…An instructive example for such an approach is O’Brien’s concise synthesis of ent ‐ 2 (Scheme ), in which the bispidine skeleton is successively constructed using a diastereoselective Michael addition between the chiral homopipecolate 12 and the α‐bromomethyl acrylate 11 as the key step 35c. “Inside‐out” approaches,35a,b,f by contrast, start with the stereoselective construction of a bispidine core precursor, to which the outer rings or substituents are attached. This strategy usually requires more steps, but will allow a maximum of flexibility and modularity, although this advantage has not yet been exploited in bispidine chemistry 38.…”

“…[30,31,34] The enantioselective total synthesis of core-chiral bispidine ligandsa nd natural products is still ac onsiderable task. [35,36] The existing approaches can loosely be categorized in "outside-in"a nd "inside-out" according to the strategy used. [37] In the former ones, [35c-e,g-k] the bispidine core is assembled in the final stages from individual precursors that already possess the later-on outer rings or substituents.…”