Whole-cell Mediated Baeyer-Villiger Oxidation of Functionalized Bicyclo[3.3.0]ketones by Recombinant E. coli

Abstract

Recombinant whole cells of Escherichia coli overexpressing Acinetobacter sp. NCIMB 9871 cyclohexanone monooxygenase (E.C. 1.14.13.22) have been utilized for the Baeyer-Villiger oxidation of functionalized bicyclo[3.3.0]ketones. Prochiral substrates were designed to probe the impact of polarity and spatial configuration of the functional groups on conversion and enantioselectivity. The data give additional insight into the steric requirements of the active site of the enzyme for high optical purity. The synthetic utility of the engineered E. coli strain is demonstrated and contributions to the non-natural substrate profile available so far are provided.

Key words

biocatalysis - recombinant whole-cell biotransformation - cyclohexanone monooxygenase - Baeyer-Villiger oxidation - substrate profiling - enantioselectivity

References

• 1 Krow GR. Org. React.  1993,  43:  251 
• 2 Bolm C. Schlingloff G. Weickhardt K. Ang. Chem., Int. Ed. Engl.  1994,  33:  1848 
• 3 Gusso A. Baccin C. Pinna F. Strukul G. Organometallics  1994,  13:  3442 
• 4 Bolm C. Schlingloff G. J. Chem. Soc., Chem. Commun.  1995,  1247 
• 5 Bolm C. Schlingloff G. Bienewald F. J. Mol. Catal. A: Chemical  1997,  117:  347 
• 6 Bolm C. Luong TKK. Schlingloff G. Synlett  1998,  1151 
• 7 Strukul G. Varagnolo A. Pinna F. J. Mol. Catal. A: Chemical  1997,  117:  413 
• 8 Bolm C. Beckmann O. Kühn T. Palazzi C. Adam W. Rao PB. Saha-Möller CR. Tetrahedron: Asymmetry  2001,  12:  2441 
• 9 Uchida T. Katsuki T. Tetrahedron Lett.  2001,  42:  6911 
• 10 Walsh CT. Chen Y.-CJ. Angew. Chem.  1988,  100:  342 
• 11 Willetts A. Trends Biotechnol.  1997,  15:  55 
• 12 Roberts SM. J. Mol. Catal. B: Enzym.  1998,  4:  111 
• 13 Stewart JD. Curr. Org. Chem.  1998,  2:  195 
• 14a Kelly DR. Chim. Oggi  2000,  18:  33 
• 14b Kelly DR. Chim. Oggi  2000,  18:  52 
• 15 Trudgill PW. In Microbial Degradation of Organic Compounds   Vol. 13:  Gibson DT. Marcel Dekker; New York: 1984.  p.131 
• 16 Donoghue NA. Norris DB. Trudgill PW. Eur. J. Biochem.  1976,  63:  175 
• 17 Taschner MJ. Black DJ. J. Am. Chem. Soc.  1988,  110:  6892 
• 18 Alphand V. Archelas A. Furstoss R. Tetrahedron Lett.  1989,  30:  3663 
• 19 Levitt MS. Newton RF. Roberts SM. Willetts AJ. J. Chem. Soc., Chem. Commun.  1990,  619 
• 20 Taschner MJ. Peddada L. J. Chem. Soc., Chem. Commun.  1992,  1384 
• 21 Furstoss R. Petit F. Tetrahedron: Asymmetry  1993,  4:  1341 
• 22 Gagnon R. Grogan G. Levitt MS. Roberts SM. Wan PWH. Willetts AJ. J. Chem. Soc., Perkin Trans. 1  1994,  2537 
• 23 Adger B. Bes MT. Grogan G. McCague R. Pedragosa-Moreau S. Roberts SM. Villa R. Wan PWH. Willetts AJ. J. Chem. Soc., Chem. Commun.  1995,  1563 
• 24 Petit F. Furstoss R. Synthesis  1995,  1517 
• 25 Lebreton J. Alphand V. Furstoss R. Tetrahedron Lett.  1996,  37:  1011 
• 26 Wong C.-H. Whitesides GM. J. Am. Chem. Soc.  1981,  103:  4890 
• 27 Tishkov VI. Galkin AG. Marchenko GN. Tsyganokov YD. Egorov HM. Biotechnol. Appl. Biochem.  1993,  18:  201 
• 28 Seelbach K. Riebel B. Hummel W. Kula M.-R. Tishkov VI. Egorov HM. Wandrey C. Kragl U. Tetrahedron Lett.  1996,  37:  1377 
• 29 Vogel M. Scharz-Linek U. Bioorg. Chem.  1999,  102 
• 30 Schwarz-Linek U. Krödel A. Ludwig F.-A. Schulze A. Rissom S. Kragl U. Tishkov VI. Vogel M. Synthesis  2001,  947 
• 31 Kayser M. Chen G. Stewart J. Synlett  1999,  153 
• 32 Chen G. Kayser MM. Mihovilovic MD. Mrstik ME. Martinez CA. Stewart JD. New J. Chem.  1999,  23:  827 
• 33 Mihovilovic MD. Chen G. Wang S. Kyte B. Rochon F. Kayser MM. Stewart JD. J. Org. Chem.  2001,  66:  733 
• 34 Mihovilovic MD. Müller B. Kayser MM. Stewart JD. Fröhlich J. Stanetty P. Spreitzer H. J. Mol. Catal. B: Enzym.  2001,  11:  349 
• 35 For an alternative E. coli expression system for CHMO see: Doig SD. O’Sullivan LM. Patel S. Ward JM. Woodley JM. Enzyme Microbiol. Technol.  2001,  28:  265 
• 36 Application of the above system for whole-cell biotransformations: Simpson HD. Alphand V. Furstoss R. J. Mol. Catal. B: Enzym.  2001,  16:  101 
• 37 Izawa H. Shirai R. Kawasaki H. Kim H.-D. Koga K. Tetrahedron Lett.  1989,  30:  7221 ; and references therein
• 38 Leonard J. Ouali D. Rahman SK. Tetrahedron Lett.  1990,  31:  739 
• 39 Zanoni G. Agnelli F. Meriggi A. Vidari G. Tetrahedron: Asymmetry  2001,  12:  1779 
• 40 Piers E. Karunaratne V. Can. J. Chem.  1987,  67:  160 
• 41 Huffman JW. Cooper MM. Miburo BB. Pennington WT. Tetrahedron  1992,  38:  8213 
• 42 Lok R. Coward JK. J. Org. Chem.  1974,  39:  2377 
• 43 Pak-Tsun H. Davies N. J. Org. Chem.  1984,  49:  3027 
• 44 Bose AK. Lal B. Tetrahedron Lett.  1973,  40:  3937 
• 45 Chen Y. Xiong Z. Zhou G. Yang J. Li Y. Chem. Lett.  1997,  1289 
• 46 Studier FW. Moffatt BA. J. Mol. Biol.  1986,  189:  113 
• 47 Bar R. Trends Biotechnol.  1989,  7:  2 
• 48a Mihovilovic MD. Müller B. Kayser MM. Stanetty P. Synlett  2002,  700 
• 48b

  Biotransformation of a precursor for the total synthesis of indole alkaloids with the CHMO expression system gave preferred formation of the (-)-4aS,8aS lactone based on the sign of specific rotation.

49

Physical and spectroscopic data of lactones 2:
4a S-cis -Hexahydro-cyclopenta[ c ]pyran-3(1 H )-one(2a). Colorless oil; ¹H NMR (200 MHz, CDCl₃): δ = 1.20-2.08 (m, 6 H), 2.25-2.69 (m, 4 H), 4.00 (dd, J = 7 Hz, J = 20 Hz, 1 H), 4.37 (dd, J = 7 Hz, J = 20 Hz, 1 H); ¹³C NMR (50 MHz, CDCl₃): δ = 25.0 (t), 28.9 (t), 34.2 (t), 34.3 (t), 34.4 (d), 36.3 (d), 67.4 (t), 173.4 (s).
4a S- (4aα,6β,7aα)-Hexahydro-6-methoxy-cyclopenta [ c ]pyran-3(1 H )-one(2b). Colorless oil; ¹H NMR (400 MHz, CDCl₃): δ = 1.50-1.65 (m, 2 H), 1.82-2.10 (m, 2 H),
2.40-2.65 (m, 4 H), 3.23 (s, 3 H), 3.72-3.83 (m, 1 H, H6), 4.08 (dd, J = 14 Hz, J = 7 Hz, 1 H), 4.31 (dd, J = 14 Hz, J = 7 Hz, 1 H); ¹³C NMR (100 MHz, CDCl₃): δ = 32.8 (d), 33.8 (t), 34.9 (t), 35.2 (d), 38.0 (t), 56.4 (q), 69.9 (t), 82.3 (d), 173.8 (s).
4a S- (4aα,6α,7aα)-Hexahydro-6-methoxy-cyclopenta [ c ]pyran-3(1 H )-one(2c). Colorless oil; ¹H NMR (400 MHz, CDCl₃): δ = 1.24-1.44 (m, 1 H), 1.52-1.68 (m, 1 H),
2.00-2.90 (m, 6 H), 3.29 (s, 3 H), 3.80-3.92 (m, 1 H), 4.10 (dd, J = 14 Hz, J = 7 Hz, 1 H), 4.35 (dd, J = 14 Hz, J = 7 Hz, 1 H); ¹³C NMR (100 MHz, CDCl₃): δ = 32.1 (d), 34.1 (t), 34.2 (t), 34.4 (d), 38.4 (t), 55.7 (q), 69.7 (t), 81.4 (d), 173.6 (s).
4a R- (4aα,6β,7aα)-6-Chloro-hexahydro-cyclopenta [ c ]pyran-3(1 H )-one(2d). Colorless crystals, mp 90-92 °C; ¹H NMR (400 MHz, CDCl₃): δ = 1.58-1.68 (m, 1 H),
1.70-1.81 (m, 1 H), 2.30-2.70 (m, 6 H), 4.05-4.15 (m, 1 H), 4.20-4.30 (m, 2 H); ¹³C NMR (100 MHz, CDCl₃): δ = 32.8 (d), 34.2 (t), 35.1 (d), 38.8 (t), 43.1 (t), 56.6 (d), 69.2 (t), 172.7 (s).
4a R- (4aα,6α,7aα)-6-Chloro-hexahydro-cyclopenta [ c ]pyran-3(1 H )-one(2e). Colorless crystals, mp 88-90 °C; ¹H NMR (400 MHz, CDCl₃): δ = 1.60-1.80 (m, 1 H), 1.92-2.10 (m, 1 H), 2.20-2.50 (m, 3 H), 2.65-3.20 (m, 3 H), 4.10 (dd, J = 14 Hz, J = 7 Hz, 1 H), 4.45-4.55 (m, 1 H); ¹³C NMR (100 MHz, CDCl₃): δ = 32.2 (d), 33.7 (t), 34.5 (d), 39.5 (t), 43.5 (t), 61.4 (d), 69.1 (t), 172.8 (s).