Optically active 1-(benzofuran-2-yl)ethanols and ethane-1,2-diols by enantiotopic selective bioreductions
Introduction
(Benzofuran-2-yl)carbinols exhibit various biological activities. Such derivatives were investigated as antibacterial1 or antifungal agents.1., 2. Moreover, optically active 2-(2-tert-butylamino-1-hydroxyethyl)benzofurans were investigated as β-blockers.3 2-Substituted benzofurans can inhibit the HIV-1 reverse transcriptase4 or act as antiaging compounds.5
Baker's yeast reduction of hydroxymethyl ketones6., 7., 8., 9., 10., 11., 12., 13., 14., 15., 15.(a), 15.(b), 16. and acetoxymethyl ketones10., 11., 14., 16. proved to be useful for production of opposite enantiomeric forms of 1,2-diols (Fig. 1). Ketones with a relatively small and hydrophilic hydroxymethyl group were all reduced from the same face, whereas the acetoxymethyl ketones were reduced with the opposite enantiotopic preference. This inversion in the sense of enantiomeric preference (Fig. 1) was demonstrated by baker's yeast reductions of phenacyl alcohols and their acetates11., 15., 15.(a), 15.(b) or of 3-O-protected dihydroxyacetone derivatives.16
Recently, we developed a method for the preparation of similar hydroxymethyl and acetoxymethyl ketones bearing benzofuran-2-yl substituents.17
Thus, 1-(benzofuran-2-yl)-2-hydroxyethanones 4a–c were obtained from methyl ketones 1a–c via their transformation into bromomethyl ketones 2a–c and subsequent conversion into acetoxymethyl ketones 3a–c followed by a mild enzymatic ethanolysis (Fig. 2).
With the 1-(benzofuran-2-yl)ethanones 1a–d, 1-(benzofuran-2-yl)-2-hydroxyethanones 4a–c and 2-acetoxy-1-(benzofuran-2-yl)-ethanones 3a–c in our hands, we thought it worthwhile investigating their enantiotopic selective reduction by baker's yeast for the preparation of optically active (benzofuran-2-yl)carbinols.
Section snippets
Results and discussion
First, reduction of 1-(benzofuran-2-yl)etanone 1a was studied under fermenting and non-fermenting conditions. Reduction of the 1a with the fermenting system (80% yield, 2 days, 20% ee) was faster but less selective. Therefore, the non-fermenting system (60% yield, 7 days, 55% ee) was applied for reduction of the further (benzofuran-2-yl)ethanones 1b–d as well (Fig. 3, Table 1). The enantiomeric composition of the products were precisely determined by GC and HPLC on chiral columns (see 3.5
Analytical methods
The 1H and 13C NMR spectra were recorded in CDCl3 solution on a Brucker DRX-500 spectrometer operating at 500 and 125 MHz, respectively. Chemical shifts are expressed in ppm values from TMS as internal standard. In 1H NMR measurements, long relaxation time (D1=20 s) was applied for enhancing the accuracy of the integration. IR spectra were recorded in KBr on a Specord 2000 spectrometer and the wavenumbers are reported in cm−1. GC analyses were made by an Agilent 4890D gas chromatograph (carrier
Conclusion
Baker's yeast mediated enantiotopic selective reduction of (benzofuran-2-yl)ketones proved to be a convenient method for preparation of optically active (benzofuran-2-yl)carbinols. Reduction of 1-(benzofuran-2-yl)ethanones 1a–d yielded secondary alcohols (S)-5a–d with moderate to good enantiomeric excess [from 55 to 87% ee], whereas reduction of 1-(benzofuran-2-yl)-2-hydroxyethanones 4a–c and 2-acetoxy-1-(benzofuran-2-yl)ethanones (3a–c) provided both enantiomeric forms of diols (S)-6a–c and (R
Acknowledgements
Financial support for the Hungarian OTKA Foundation (T-033112), for the Hungarian Ministry of Education, National R&D Project (NKFP3-35-2002) and the Romanian Ministry of Education and Research (AT-18/600) is gratefully acknowledged. C.P. and C.M. thank Domus Hungarica and Agora Foundation.
References (28)
- et al.
Eur. J. Med. Chem. Chim. Ther.
(1995) - et al.
Bioorg. Med. Chem.
(1998) - et al.
Tetrahedron: Asymmetry
(1998) - et al.
Tetrahedron: Asymmetry
(1999) - et al.
J. Chem. Soc., Perkin 1
(2002) - et al.
Arch. Pharm. (Weinheim)
(1981) - et al.
J. Med. Chem.
(1985) - et al.
J. Med. Chem.
(1993) CNS Drug Rev.
(2001)- et al.
Org. Synth. Coll.
(1943)