Lipase-catalysed enantioselective kinetic resolution of rac-lipidic alkynylcarbinols and a C5 synthon thereof via a hydrolysis approach

Abstract

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Phenyl dialkynylcarbinols, a Bioinspired Series of Synthetic Antitumor Acetylenic Lipids

“…1 H NMR (300 MHz, CDCl 3 ): δ (ppm) 7.32−7.26 (m, 2H), 7.22 (td, J = 7.3, 1.0 Hz, 1H), 7.16 (dt, J = 7.6, 1.7 Hz, 1H), 5.34 (dd, J = 7.5, 2.3 Hz, 1H), 2.61 (d, J = 2.3 Hz, 1H), 2.57 (t, J = 7.5 Hz, 2H), 2.41 (d, J = 7.6 Hz, 1H, OH), 1.65−1.50 (m, 2H), 1.40−1.10 (m, 10H), 0.88 (t, J = 6.7 Hz, 3H). 13 1-(6-Octylnaphthalen-2-yl)penta-1,4-diyn-3-ol (20). The crude mixture was purified by flash column chromatography using 20% diethyl ether in pentane.…”

“…Following the systematic structural modulation of a prototypical lipidic alkynylcarbinol (LAC) (Figure ), it was previously shown that subtle modifications of the molecule can dramatically impact its cytotoxicity. − In particular, the absolute configuration and the steric and/or electronic environment of the chiral carbinol center are determining factors, as highlighted by the increased potency of the dialkynylcarbinol (DAC) series (Figure ). Structural evolution of synthetic LACs led to an overall 1000-fold increase in toxicity against HCT116 colon cancer cells compared to the natural product of reference (Figure ).…”

“…H NMR (400 MHz, CDCl 3 ): δ (ppm) 7.38 (d, J = 8.2 Hz, 2H), 7.13 (d, J = 8.3 Hz, 2H), 5.34 (br s, 1H), 2.65− 2.55 (m, 3H), 2.33 (br d, J = 6.1 Hz, 1H, OH), 1.65−1.50 (m, 2H), 1.35−1 20. (m, 18H), 0.88 (t, J = 6.7 Hz, 3H).13 C NMR (75 MHz, CDCl 3 ): δ (ppm) 144.4, 131.9, 128.6, 118.9, 85.2, 84.9, 81.1, 73.0,52.7, 36.1, 32.1, 31.3, 29.8, 29.8, 29.7, 29.6, 29.5, 29.4, 22.8, 14.3.…”

Exploring the chemical reactivity of triisopropylsilyl dialkynyl methanol for the synthesis of dialkynylcarbinol-related compounds

“…The chiral mono C-protected dialkynylcarbinol 1-(triisopropyl)silyl)penta-1,4-diyn-3-ol (2) (Figure 2) is a highly functionalized C5 organic framework readily available in either racemic 14 or enantiopure forms. 15 In 2020, a lipase-mediated enzymatic kinetic resolution (EKR) was successfully implemented to produce enantioenriched 2 from the acetate precursor rac-3 (Scheme 1). 15 According to this hydrolytic approach, (R)-2 and its acetylated enantiomer (S)-3 were obtained with an enantiomeric excess (ee) >99%, a conversion (c) of 50% and an enantioselectivity (E) >200, thanks to the use of a lipase from Thermomyces lanuginosus immobilized on immobead-150 (TLL).…”

Bio-Approach for Obtaining Enantiomerically Pure Clopidogrel with the Use of Ionic Liquids

“…A high selectivity, more favorable reaction conditions, and biocompatibility are just a few of the positive characteristics that make enzyme-mediated transformations so valued as a potent alternative instrument in organic synthesis. Since organic synthesis relies on performing a stereoselective biotransformation, and is therefore significantly less expensive than using a “chiral pool,” kinetic resolution (racemate resolution) with the use of enzymes is one of the most widely used techniques [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. It also avoids the use of environmentally hazardous and toxic chemical compounds.…”