Enzymatic Kinetic Resolution of 2-Piperidineethanol for the Enantioselective Targeted and Diversity Oriented Synthesis

Abstract

2-Piperidineethanol (1) and its corresponding N-protected aldehyde (2) were used for the synthesis of several natural and synthetic compounds. The existence of a stereocenter at position 2 of the piperidine skeleton and the presence of an easily-functionalized group, such as the alcohol, set 1 as a valuable starting material for enantioselective synthesis. Herein, are presented both synthetic and enzymatic methods for the resolution of the racemic 1, as well as an overview of synthesized natural products starting from the enantiopure 1.

Synthesis of Pironetin–Dumetorine Hybrids as Tubulin Binders

“…[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). [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).…”

“…[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]…”

Total Synthesis of (–)-Anaferine: A Further Ramification in a Diversity-Oriented Approach

“…[ 3.7. Synthesis of (R)-tert-butyl 2-((2S,4R)-4-acrylamido-2-((tert-butyldimethylsilyl)oxy) hept-6-en-1-yl) piperidine-1-carboxylate (11) Compound 10 (0.558 g, 1.31 mmol) was dissolved in anhydrous CH 2 Cl 2 (5.5 mL) and cooled at 0 • C. Anhydrous TEA (547 µL, 3.92 mmol) was added and the reaction was stirred for 10 min. Acryloyl chloride (160 µL, 1.96 mmol) was added dropwise; the mixture was warmed to r.t. and stirred for 5 h. At that point, cold water (0 • C) was added.…”

“…In this project, the ideal starting point to achieve structural diversification proved to be the 2-piperidine ethanol (1), a cheap and commercially available racemic product that incorporates the fundamental highlighted 2-substituted-piperidine moiety. Our library is composed by natural products (such as aloperine, coniine, boehmeriasin A and sedum alkaloids [11][12][13][14]), and synthetic derivatives [15][16][17][18], as depicted in Figure 2. We are currently trying to further enrich our library with new scaffolds.…”

Novel (S)-Selective Hydrolase from Arthrobacter sp. K5 for Kinetic Resolution of Cyclic Amines

“…Optically active amines can be prepared from racemic amine by diastereomeric salt formation using chiral carboxylic acids [17] or by stereoselective bioconversion of racemic N-acyl amine using enzymes [18][19][20]. Several studies on chiral cyclic amines' preparation via chemical or enzymatic resolution have been reported (Scheme 1) [21][22][23][24][25][26][27][28][29][30][31][32][33]. In the enzy- Optically active amines can be prepared from racemic amine by diastereomeric salt formation using chiral carboxylic acids [17] or by stereoselective bioconversion of racemic N-acyl amine using enzymes [18][19][20].…”