Kinetic and Dynamic Kinetic Resolution of Secondary Alcohols with Ionic-Surfactant-Coated Burkholderia cepacia Lipase: Substrate Scope and Enantioselectivity

Abstract

Forty-four different secondary alcohols, which can be classified into several types (II-IX), were tested as the substrates of ionic surfactant-coated Burkholderia cepacia lipase (ISCBCL) to see its substrate scope and enantioselectivity in kinetic and dynamic kinetic resolution (KR and DKR). They include 6 boron-containing alcohols, 24 chiral propargyl alcohols, and 14 diarylmethanols. The results from the studies on KR indicate that ISCBCL accepted most of them with high enantioselectivity at ambient temperature and with useful to high enantioselectivity at elevated temperatures. In particular, ISCBCL displayed high enantioselectivity toward sterically demanding secondary alcohols (types VIII and IX) which have two bulky substituents at the hydroxymethine center. DKR reactions were performed by the combination of ISCBCL with a ruthenium-based racemization catalyst at 25-60 °C. Forty-one secondary alcohols were tested for DKR. About half of them were transformed into their acetates of high enantiopurity (>90% ee) with good yields (>80%). It is concluded that ISCBCL appears to be a superb enzyme for the KR and DKR of secondary alcohols.

Dynamic Kinetic Resolution of Diarylmethanols with an Activated Lipoprotein Lipase

“…(R)-(4-Isopropylphenyl)(m-tolyl)methyl acetate (8c): 71% yield, 91% ee; [α] D 25 +15.5 (c = 0.9, CHCl 3 ); 1 H NMR (300 MHz, CDCl 3 , ppm): δ 7.26-7.05 (m, 8H), 6.81 (s, 1H), 2.92-2.83 (m, 1H), 2.33 (s, 3H), 2.15 (s, 3H), 1.23-1.21 (d, J = 6.9 Hz, 6H); 13 C NMR (75 MHz, CDCl 3 , ppm): 170.1, 148.5, 140.2, 138.1, 137.6, 128.5, 128.3, 127.6, 127.1, 126.5, 124.0, 76.5, 33.7, 23.9, 21.4, 21.3; HPLC conditions (hydrolysis product: alcohol-form): Whelk-O1, n-hexane/2-propanol = 95/5, flow rate = 1.0 mL/min, UV = 217 nm, retention times 7.9 min (R), 9.0 min (S); TOF-MS (ESI+) calcd for [C 19 H 22 O 2 -OAc] + 223.14868, found 223.14671. (R)-(4-Fluorophenyl)(4-isopropylphenyl)methyl acetate (8d): 91% yield, 91% ee; The analytical data were in good agreement with the literature values 41. …”

“…39 Recently, we reported that an ionic-surfactant-coated Burkholderia cepacia lipase (ISCBCL) was highly active in organic solvent 40 and accepted a wider range of secondary alcohols in the DKR. 41 Unfortunately, the DKR of diarylmethanols with this enzyme was not satisfactory. Later, we communicated that a lipoprotein lipase 42 (LPL) from Burkholderia species was also highly active in organic solvent if it was coated with both dextrin (D) and ionic surfactant (1) via lyophilization.…”

Chemoenzymatic Dynamic Kinetic Resolution: A Powerful Tool for the Preparation of Enantiomerically Pure Alcohols and Amines

“… 86 By combining catalyst 8 with ionic surfactant-coated Burkholderia cepacia lipase, the DKR of a variety of secondary alcohols was accomplished at 25–60 °C, including α-arylpropargyl alcohols, B(pin)-substituted benzylic alcohols, γ-chloro alcohols, and TMS-propargyl alcohols. 55 , 87 …”

Expanding dynamic kinetic protocols: transaminase-catalyzed synthesis of α-substituted β-amino ester derivatives

“…Compounds 1b-k were achieved through treatment of the β-keto ester precursors with the corresponding alkyl halide in basic medium. 4a,d In a subsequent step, adapting a protocol described by Brandt and co- 60 workers, 13 ultrasonication of these derivatives under the presence of benzylamine at 30 ºC smoothly afforded the (Z)-N-benzylated enamine esters 4b-k in excellent yields. Then, the corresponding N-protected β-amino esters syn-5b-k and anti-6b-k were obtained as diastereoisomeric mixtures by reduction of the C=C double 65 bond with NaBH(OAc) 3 at 0 ºC in high yields.…”