Short enantioselective synthesis of sedridines, ethylnorlobelols and coniine via reagent-based differentiation

Synthesis of Pironetin–Dumetorine Hybrids as Tubulin Binders

“…[6] Thus, the use of (-)-DIP-Cl furnished separable diastereoisomers 2a and 3a characterized by the S configuration at position 2′; the use of (+)-DIP-Cl secured the acquisition of compounds 4a and 5a. The assignment of the structures was confirmed on the basis of previously reported spectroscopic data [11,13] and by performing the same reaction on small scale using, as substrates, the pure enantiomers of aldehyde 1. [6] In particular, the reaction of (S)-1 with (-)-DIP-Cl gave 2a as a single product and confirmed that the configuration of the newly formed stereogenic center is dictated by the chirality of DIP-Cl.…”

“…[14] Brown's asymmetric allylation with the B-allyl di-isopinocampheylborane, prepared from (+)-di-isopinocampheylboron chloride (DIP-Cl) and allylmagnesium bromide, [37] enabled formation of allylic alchols 2a-5a with complete stereocontrol at C2′ (numbering system of the target compound) thus furnishing two enantiopure diastereoisomers (on the basis of HPLC traces). The assignment of the structures was confirmed on the basis of previously reported spectroscopic data [11,13] and by performing the same reaction on small scale using, as substrates, the pure enantiomers of aldehyde 1. The assignment of the structures was confirmed on the basis of previously reported spectroscopic data [11,13] and by performing the same reaction on small scale using, as substrates, the pure enantiomers of aldehyde 1.…”

“…[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]…”

“…Nature is continually providing interesting inspirations for the discovery, design and synthesis of novel drugs. [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. [33] We were attracted by the presence of the 5,6-dihydropyrone ring which serves as an effective Michael acceptor with the amino group of a lysine residue in the binding site of α-tubulin.…”

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

“…Considering our interest in natural products, we took advantage of this approach to synthesize some alkaloids (aloperine, [6] different sedum alkaloids, [7] dumetorine, epidihydropinidine, coniine, [8] boehmeriasin A [9] ) but also some synthetic derivatives, such as polyheterocyclic derivatives [10] and hybrid compounds ( Figure 1). Among the methods useful for the gen- cemic form, contains two handles -the piperidine nitrogen and the hydroxyl group -which can be easily further functionalized, increasing in this way the structural complexity.…”