Chemical Properties

White needles

Uses

(S)?-?(-?)?-?1-?(4-?Pyridyl)?ethanol is a building block used in the synthesis of macrocycles which act as hydrogenation catalysts as well as other pharmaceutical agents

Synthesis

The general procedure for the synthesis of (S)-4-pyridine-1-ethanol from 4-acetylpyridine was as follows: first, the relative activities of the 26 substrates were assessed by a previously described assay protocol and the enzyme-to-substrate concentration ratio was adjusted. In this procedure, the activity of α-chloroacetophenone was used as a benchmark (set at 100%). Subsequently, the reduction reaction of aromatic ketones was determined enantioselectively using a NADH regeneration system consisting of KcDH purified from Bacillus subtilis CGMCC 1.1398 and glucose dehydrogenase (GDH). The specific reaction conditions were as follows: 0.5 mM NAD+, 10 mM ketone substrate, 1 U KcDH, 50 mg glucose, and 2 U GDH were added to 1 mL of 50 mM potassium phosphate buffer (pH 7.0). the reaction was carried out for 16 h. After the reaction was carried out, the reaction mixture was homogenized into two parts. One portion was terminated by adding an equal volume of methanol and subsequently analyzed by HPLC to determine the conversion; the other portion was extracted with ethyl acetate and further analyzed for enantiomeric excess (ee). The chiral products were analyzed by HPLC or GC methods, and the specific operating conditions are detailed in Supplementary Table S1.

Purification Methods

Purify it by recrystallisation from pet ether. The m recorded after sublimation was 59.9-60.2o, and 55o after crystallisation from *C6H6/pet ether or pet ether/*C6H6. The (-)-di-O-benzoyl tartrate salt has m 146-148o (from EtOH). [UV, ORD: Harelli & Samori J Chem Soc Perkin Trans 2 1462 1974.] The racemate recrystallises from Et2O with m 74-76o,b 90-94o/1mm. The picrate has m 125-126o (from *C6H6). [Ferles & Attia Collect Czech Chem Commun 38 611 1973, UV, NMR: Nielson et al. J Org Chem 29 2898 1964, Beilstein 21 III/IV 522, 21/2 V 217.]

References

[1] Organic Letters, 2000, vol. 2, # 12, p. 1749 - 1751
[2] Synthesis, 2009, # 14, p. 2413 - 2417
[3] Advanced Synthesis and Catalysis, 2014, vol. 356, # 10, p. 2293 - 2302
[4] Tetrahedron Asymmetry, 2002, vol. 13, # 20, p. 2201 - 2204
[5] Advanced Synthesis and Catalysis, 2016, vol. 358, # 24, p. 4006 - 4018