Download PDF
Synlett 2016; 27(11): 1677-1681
DOI: 10.1055/s-0035-1561942
letter
© Georg Thieme Verlag Stuttgart · New York

Stereoselectivity in the Reduction of Bicyclic Tetramates

Laia Josa-Culleré
Department of Chemistry, Chemistry Research Laboratory, The University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK   Email: mark.moloney@chem.ox.ac.uk
,
Mark G. Moloney*
Department of Chemistry, Chemistry Research Laboratory, The University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK   Email: mark.moloney@chem.ox.ac.uk
,
Amber L. Thompson
Department of Chemistry, Chemistry Research Laboratory, The University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK   Email: mark.moloney@chem.ox.ac.uk
› Author Affiliations
Further Information

Publication History

Received: 11 February 2016

Accepted: 28 February 2016

Publication Date:
22 March 2016 (online)

    Permissions and Reprints All articles of this category


Abstract

The reduction of bicyclic tetramates can be achieved with high levels of diastereocontrol, but small changes in the substitution of the bicyclic lactam system can lead to changes in the steric bias of the concave/convex system. The tetramates and pyroglutamates prepared in this work exhibited limited antibacterial activity.

Key words

tetramate - reduction - lactam - stereoselectivity - pyroglutamate

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1561942.
  • Supporting Information
 

  • References and Notes

    • 1a Omura S, Fujimoto T, Otoguro K, Matsuzaki K, Moriguchi R, Tanaka H, Sasaki Y. J. Antibiot. 1991; 44: 113
      CrossrefPubMed
    • 1b Omura S, Fujimoto T, Matsuzaki K, Moriguchi R, Kosuge K, Furuya T, Fujita S, Nakagawa A. J. Antibiot. 1991; 44: 117
      CrossrefPubMed
  • 2 Ishihara J, Hatakeyama S. Chem. Rec. 2014; 14: 663
    Crossref
    • 3a Barrett AG. M, Head J, Smith ML, Stock NS. Chem. Commun. 1999; 133
    • 3b Schwartz RE, Helms GL, Bolessa EA, Wilson KE, Giacobbe RA, Tkacz JS, Bills GF, Liesch JM, Zink DL, Curotto JE, Pramanik B, Onishi JC. Tetrahedron 1994; 50: 1675
      Crossref
  • 4 Jeong Y.-C, Moloney MG. Future Med. Chem. 2015; 7: 1861
    CrossrefPubMed
  • 5 Andrews MD, Brewster AG, Crapnell KM, Ibbett AJ, Jones T, Moloney MG, Prout K, Watkin D. J. Chem. Soc., Perkin Trans. 1 1998; 223
  • 6 Seebach D, Aebi JD. Tetrahedron Lett. 1984; 25: 2545
    Crossref
  • 7 Galeotti N, Poncet J, Chiche L, Jouin P. J. Org. Chem. 1993; 58: 5370
    Crossref
  • 8 Andrews MD, Brewster AG, Moloney MG. J. Chem. Soc., Perkin Trans. 1 2002; 80
  • 9 Single-crystal X-ray diffraction data were collected at 150 K with an Oxford Diffraction (Rigaku) SuperNova diffractometer (using λ = 1.54180 Å) and processed with CrysAlisPro as per the SI (CIF). The structure was solved with SIR9215 and refined with CRYSTALS16 including the Flack × parameter17 which refined to –0.008(8) (unrestrained). Bayesian analysis18 of the Bijvoet pairs gave the Hooft y parameter as –0.002(4) and the probability that the structure was the correct hand of >99.99% given that the crystal is either enantiopure or a racemic twin. The asymmetric unit contains three molecules, all with the same stereochemistry. Full crystallographic data (in CIF format) is available as ESI and has been deposited with the Cambridge Crystallographic Data Centre (reference code CCDC 1452987). The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
  • 10 Bailey JH, Byfield AT. J, Davis PJ, Foster AC, Leech M, Moloney MG, Müller M, Prout CK. J. Chem. Soc., Perkin Trans. 1 2000; 1977
  • 11 Mitsunobu O, Yamada M. Bull. Chem. Soc. Jpn. 1967; 40: 2380
    Crossref
    • 12a Smith B, Warren SC, Newton GG. F, Abraham EP. Biochem. J. 1967; 103: 877
      Crossref
    • 12b Bioassay of Penicillin Products: Microbiological assays were performed by the hole-plate method with the test organism Staphylococcus aureus N.C.T.C. 6571 or Escherichia coli X580. Solutions (100 μL) of the compounds to be tested (4 mg/mL) were loaded into wells in bioassay plates and incubated overnight at 37 °C. The diameters of the resultant inhibition zones were measured.
  • 13 Jeong Y.-C, Moloney MG. Synlett 2009; 2487
    Article in Thieme Connect
  • 14 Marvin was used for drawing, displaying, and characterizing chemical structures, substructures, and reactions, Marvin 5.2.1, 2009, ChemAxon (http://www.chemaxon.com). Calculator Plugins were used for structure property prediction and calculation, Marvin 5.2.5.1, 2009, ChemAxon (http://www.chemaxon.com).
  • 15 Altomare A, Cascarano G, Giacovazzo G, Guagliardi A, Burla MC, Polidori G, Camalli M. J. Appl. Crystallogr. 1994; 27: 435
    Crossref
    • 16a Betteridge PW, Carruthers JR, Cooper RI, Prout K, Watkin DJ. J. Appl. Crystallogr. 2003; 36: 1487
      Crossref
    • 16b Parois P, Cooper RI, Thompson AL. Chem. Cent. J. 2015; 9: 30
      Crossref
    • 16c Cooper RI, Thompson AL, Watkin DJ. J. Appl. Crystallogr. 2010; 43: 1100
      Crossref
    • 17a Flack HD. Acta Crystallogr., Sect. A: Found. Crystallogr. 1983; 39: 876
      Crossref
    • 17b Flack HD, Bernardinelli G. J. Appl. Crystallogr. 2000; 33: 1143
      Crossref
    • 17c Thompson AL, Watkin DJ. Tetrahedron: Asymmetry 2009; 20: 712
      Crossref
    • 17d Thompson AL, Watkin DJ. J. Appl. Crystallogr. 2011; 44: 1017
      Crossref
  • 18 Hooft RW. W, Straver LH, Spek AL. J. Appl. Crystallogr. 2008; 41: 96
    Crossref
  • 19 General procedure for the decarboxylation of tetramic acids. Tetramic acid 2a–c (1.0 equiv) and NaOH (2.0 equiv) in a 4:1:1 mixture of THF–MeOH–H2O was heated at reflux for 8 h and then cooled to room temperature. The mixture was acidified with 2 M aq HCl, extracted with EtOAc, dried over Na2SO4 and concentrated in vacuo. The crude product was dissolved in MeCN and heated at reflux for 5 h then cooled to room temperature. The mixture was acidified with 2 M aq HCl, extracted with EtOAc, dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography to give decarboxylated tetramic acids 4a–c. Data for (2R,5S)-1-Aza-2-(tert-butyl)-6,8-dioxo-3-thiabicyclo[3.3.0]-octane (4b). Yield 33 mg (32%); off-white solid; mp 142–144 °C. Rf = 0.50 (50% EtOAc in CH2Cl2). [α]D 20 = +71.2 (c 0.8, CH2Cl2). IR: ν = 2960 (C–H), 1769 (C=O), 1699 (C=O) cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.00 (s, 9 H, C(CH 3)3), 2.84 (t, J = 10.4 Hz, 1 H, C(4)H AHB), 3.13 (app dd, J = 22.0, 1.5 Hz, 1 H, C(7)H AHB), 3.19 (dd, J = 10.4, 7.0 Hz, 1 H, C(4)HA H B), 3.31 (d, J = 22.0 Hz, 1 H, C(7)HA H B), 4.44 (dd, J = 10.0, 7.0 Hz, 1 H, C(5)H), 5.30 (s, 1 H, C(2)H). 13C NMR (100 MHz, CDCl3): δ = 26.4 (C(CH3)3), 33.3 (C(4)), 37.8 (C(CH3)3), 43.0 (C(7)), 71.5 (C(2)), 72.4 (C(5)), 170.1 (C(8)), 203.5 (C(6)). MS (ESI+): m/z = 214.1 (MH+, 91%), 236.1 (MNa+, 100%). HRMS (ESI+): found 214.08959, C10H16NO2S requires (MH+) 214.08963.
  • 20 General procedure for the reduction of tetramic acids. NaBH4 (2.2 equiv) was added portionwise at 0 °C to a solution of tetramic acids 2a–c or 4a–c (1.0 equiv) and acetic acid (9.0 equiv) in anhydrous CH2Cl2. The reaction mixture was stirred at 0 °C for 15 min and then at room temperature until starting material disappeared by TLC (typically 2 h). The reaction mixture was quenched with saturated aq NaHCO3 and extracted with EtOAc, washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was purified by flash column chromatography to give the desired alcohol 3a–c and 5a–c. Data for (2R,5R,6S)-1-Aza-2-(tert-butyl)-6-hydroxy-5-methoxycarbonyl-8-oxo-3-thiabicyclo[3.3.0]-octane (3b). Yield 101 mg (quant.); white solid; m.p. 75–77 °C. Rf = 0.38 (50% EtOAc in CH2Cl2). [α]D 20 = +18.6 (c 1.0, CH2Cl2). IR: ν = 3380 (O–H), 2956 (C–H), 1744 (C=O), 1686 (C=O) cm-1. 1H NMR (500 MHz, CDCl3): δ = 0.92 (s, 9 H, C(CH 3)3), 2.63 (d, J = 4.5 Hz, 1 H, OH), 2.74 (dd, J = 15.5, 8.0 Hz, 1 H, C(7)H AHB), 2.98 (dd, J = 16.0, 10.5 Hz, 1 H, C(7)HA H B), 3.03 (d, J = 11.5 Hz, 1 H, C(4)H AHB), 3.84 (s, 3 H, CO2CH 3), 3.90 (d, J = 11.5 Hz, 1 H, C(4)HA H B), 4.43 (ddd, J = 10.5, 8.0, 4.0 Hz, 1 H, C(6)H), 5.04 (s, 1 H, C(2)H). 13C NMR (125 MHz, CDCl3): δ = 26.6 (C(CH3)3), 38.0, 38.7 (C(4), C(CH3)3), 40.9 (C(7)), 53.1 (CO2 CH3), 72.8, C(2)), 76.6 (C(6)), 82.0 (C(5)), 171.2 (CO2CH3), 173.8 (C(8)). MS (ESI+): m/z = 274.1 (MH+, 52%), 296.1 (MNa+, 100%). HRMS (ESI+): found 296.0936, C12H19NNaO4S requires (MNa+) 296.0927. Data for (2R,5S,6S)-1-Aza-2-(tert-butyl)-6-hydroxy-8-oxo-3-thiabicyclo[3.3.0]-octane (5b). Yield 32 mg (86%); white solid; 1.9:1 mixture of diastereomers. Rf = 0.21 (50% EtOAc in CH2Cl2). IR: ν = 3369 (O–H), 2962 (C–H), 1674 (C=O) cm-1. 1H NMR (500 MHz, CDCl3) major isomer (5b’): δ = 0.96 (s, 9 H, C(CH 3)3), 2.46 (dd, J = 17.2, 3.0 Hz, 1 H, C(7)H AHB), 2.93 (dd, J = 17.2, 6.5 Hz, 1 H, C(7)HA H B), 2.97 (dd, J = 10.8, 7.2, 1 H, C(4)H AHB), 3.21 (dd, J = 10.8, 7.8 Hz, 1 H, C(4)HA H B), 4.33 (td, J = 7.5, 5.5 Hz, 1 H, C(5)H), 4.58 (ddd, J = 6.5, 5.5, 3.0 Hz, 1 H, C(6)H), 5.05 (s, 1 H, C(2)H); minor isomer (5b): δ = 0.98 (s, 9 H, C(CH 3)3), 2.51 (t, J = 10.2 Hz, 1 H, C(4)H AHB), 2.61 (dd, J = 18.0, 3.5 Hz, 1 H, C(7)H AHB), 2.83 (dd, J = 18.0, 7.5 Hz, 1 H, C(7)HA H B), 3.11 (dd, J = 10.5, 6.0 Hz, 1 H, C(4)HA H B), 4.08 (ddd, J = 10.0, 6.0, 2.0 Hz, 1 H, C(5)H), 4.29 (ddd, J = 7.5, 3.5, 2.0 Hz, 1 H, C(6)H), 5.01 (s, 1 H, C(2)H). 13C NMR (100 MHz, CDCl3) major isomer (5b’): δ = 26.5 (C(CH3)3), 30.6 (C(4)), 38.2 (C(CH3)3), 42.4 (C(7)), 66.7 (C(6)), 68.8 (C(5)), 70.8 (C(2)), 174.1 (C(8)); minor isomer (5b): δ = 26.5 (C(CH3)3), 35.0 (C(4)), 37.6 (C(CH3)3), 41.8 (C(7)), 69.5 (C(6)), 71.0 (C(2)), 73.8 (C(5)), 175.0 (C(8)). MS (ESI+): m/z = 216.1 (MH+, 97%), 238.1 (MNa+, 90%). HRMS (ESI+): found 216.10514, C10H18NO2S (MH+) requires 216.10528.