Preparation of Optically Active 1-O-Alkyl-3-O-arylsulfonyl-sn-glycerol Derivatives: Substrate Engineering in Enzyme-Mediated Enantioselective Hydrolysis

Abstract

Lipase PS catalyzes the enantioselective hydrolysis of various 2-acetyl compounds of the 1-O-alkyl-3-O-arylsulfonyl-sn-glycerol derivatives to afford the corresponding optically active compounds. Changing the structure of the 1-O-alkyl and 3-O-arylsulfonyl groups affects both the reactivity and enantioselectivity. Finally, the E value of the reaction for 2-acetyl-3-O-3,5-dimethylbenzenesulfonyl-1-O-4-methoxybenzyl-sn-glycerol is greater than 200.

enantioselective hydrolyses - enzymes - kinetic resolution - glycerol derivatives - tosylates

References and Notes

For recent reviews, see:

1a Bornscheuer UT. Kazlauskas RJ. Hydrolases in Organic Synthesis   Wiley-VCH; Weinheim: 1999. 

1b Bommarius AS. Riebel BR. Biocatalysis   Wiley-VCH; Weinheim: 2004. 

1c Faber K. Biotransformations in Organic Chemistry: A Textbook   5th ed.:  Springer; Berlin: 2004. 

1d Ghanem A. Aboul-Enein HY. Chirality  2004,  17:  1 

1e Garcia-Uradiales E. Alfonso I. Gotor V. Chem. Rev.  2005,  105:  313 

1f Bornscheuer UT. Trends and Challenges in Enzyme Technology   Springer; Berlin: 2005. 

1g Fogassy E. Nógrádi M. Kozma D. Egri G. Pálovics E. Kiss V. Org. Biomol. Chem.  2006,  4:  3011 

1h Gadler P. Faber K. Trends Biotechnol.  2007,  25:  83 

1i Ghanem A. Tetrahedron  2007,  63:  1721 

1j Gotor V. Alfonso I. Garcia-Urdiales E. Asymmetric Organic Synthesis with Enzymes   Wiley-VCH; Weinheim: 2008. 

For enzymatic hydrolysis of acyl derivatives of 1,2-diol monotosylates in an aqueous media, see:

2a Hamaguchi S. Ohashi T. Watanabe K. Agric. Biol. Chem.  1986,  50:  375 

2b Hamaguchi S. Ohashi T. Watanabe K. Agric. Biol. Chem.  1986,  50:  1629 

2c Hamaguchi S, Katayama K, Ohashi T, and Watanabe K. inventors; JP  62158250. 

2d Hamaguchi S, Kobayashi M, Katayama K, Ohashi T, and Watanabe K. inventors; JP  62209049. 

2e Kobayashi M, Hamaguchi S, Katayama K, Ohashi T, and Watanabe K. inventors; JP  62212382. 

2f Pederson RL. Liu KK.-C. Rutan JF. Chen L. Wong C.-H. J. Org. Chem.  1990,  55:  4897 

2g Chen C.-S. Liu Y.-C. Marsella M. J. Chem. Soc., Perkin Trans. 1  1990,  2559 

For enzymatic esterification of 1,2-diol monotosylates in organic solvent, see:

3a Chen C.-S. Liu Y.-C. Tetrahedron Lett.  1989,  30:  7165 

3b Chênevert R. Gagnon R. J. Org. Chem.  1993,  58:  1054 

3c Neagu C. Hase T. Tetrahedron Lett.  1993,  34:  1629 

3d Boaz NW. Zimmerman RL. Tetrahedron: Asymmetry  1994,  5:  153 

3e Boaz NW. Falling SN. Moore MK. Synlett  2005,  1615 

3f

For enzymatic hydrolysis in organic solvent, see ref. 3c. For enzymatic alcoholysis in organic solvent, see refs. 3a and 2g.

4 Saito Y, and Nakamura T. inventors; JP  10057096. For enantioselective decomposition of 1,2-diol monotosylate by microorganisms, see:

5 Shimada Y. Sato H. Minowa S. Matsumoto K. Synlett  2008,  367 

6

The racemic alcohols (±)-2, except for 2d, as the precursor of the substrates were prepared in three steps: 1) protection of the hydroxyl group of 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane, 2) 2 M aq HCl-THF, 3) TsCl, Bu₂SnO, Et₃N-CH₂Cl₂.^¹² In all cases, the resulting (±)-2 contained the regioisomers, 3-acetyl-2-O-tosyl-sn-glycerol (±)-7, as the minor product. After the enzymatic acylation of the mixture using porcine pancreas lipase (PPL, Sigma), the pure (±)-2 was obtained. The details will be reported separately. On the other hand, (±)-2d was prepared from the coupling of (±)-glycidol with TsOH, followed by selective protection of the primary hydroxyl group with TBS.

7

The absolute configuration of 2a {[α]_D ^²5 -4.19 (c 2.49, C₆H₆) (59% ee)} was confirmed by comparing the obtained optical rotation value with the reported value: lit.^¹³ [α]_D ^²5
-6.70 (c 10, C₆H₆; R form).

8 Chen C.-S. Fujimoto Y. Girdaukas G. Sih CJ. J. Am. Chem. Soc.  1982,  104:  7294 

9

The substrate with a mesyl group was quite unstable and decomposed under the enzymatic reaction conditions.

10

Compound (R)-5: [α]_D ^³0 +1.89 (c 0.90, CHCl₃; 93% ee).
Compound (S)-5: [α]_D ^²¹ -1.81 (c 0.83, CHCl₃; 95% ee); lit.^¹4 [α]_D ^²¹ +1.79 (c 5.02, CHCl₃; R form).

11

To a 200 mL Erlenmeyer flask containing (±)-6 (72.3 mg, 0.17 mmol; sub. concd, ca. 4 mM) were added of i-Pr₂O (4 mL), 0.1 M phosphate buffer (40 mL, pH 6.5), and lipase PS (30 mg). After the mixture was incubated for 24 h at 30 ˚C, the products were extracted with EtOAc and purified by flash column chromatography on SiO₂ (eluent: hexane-EtOAc, 4:1) to afford (S)-6 (26.4 mg, 37%, 99% ee) and (R)-7 (31.5 mg, 48%, 96% ee).

12 Martinelli MJ. Vaidyanathan R. Pawlak JM. Nayyar NK. Dhokte UP. Doecke CW. Zollars LMH. Moher ED. Khau VV. Kosmrlj B. J. Am. Chem. Soc.  2002,  124:  3578 

13 Byun H.-S. Bittman R. Tetrahedron Lett.  1989,  30:  2751 

14 Takano S. Goto E. Hirama M. Ogasawara K. Heterocycles  1981,  16:  381