1738
G. Athanasellis et al.
LETTER
was diluted with water and washed with diethyl ether. The aq
extract was acidified with 10% HCl in an ice water bath to
afford a white solid (1-hydroxybenzotriazole) which was
filtered off. The aq filtrate was extracted with DCM (3 ) and
the combined organic extracts were dried (Na2SO4) and
concentrated in vacuo to afford either 3-substituted tetronic
acids 4–6 as white solids or the C-acylation compounds
7–14 as oils. The oily products 7–14 were dissolved in
methanol and treated with 10% HCl for 24 h (7 and 8) or 48
h (9–14) at r.t. to afford the corresponding tetronic acids
15–21 as white solids. The solid products were filtered off,
washed with light petrol and dried in vacuo.
of the starting optically active materials and a short reac-
tion time is required in contrast to previous methodolo-
gies.11 Work currently in progress includes application of
the proposed methodology on the preparation of highly
functionalized tetronic acid derivatives with known bio-
logical activity. Also, the -hydroxy esters may serve as
attractive potential intermediates for synthesizing more
complex biologically important molecules. Additionally,
the catalytic asymmetric hydrogenation reaction of the
functionalized -hydroxy esters and tetronic acid deriva-
tives is under investigation.
(16) Spectroscopic and Analytical Data of Selected
Compounds:
3-Methoxycarbonyl Tetronic Acid (4). 59% Yield, mp:
166–167 °C. IR (KBr): 1720/1703 (C=O), 1605 (C=C)
cm–1. 1H NMR (300 MHz, CDCl3): = 3.96 (s, 3 H,
COOCH3), 4.81 (s, 2 H, CH2) ppm. 13C NMR (75 MHz,
CDCl3): = 52.3 (COOCH3), 66.0 (C-5), 100.2 (C-3), 167.0
(C-6), 169.4 (C-2), 189.4 (C-4) ppm. Anal. Calcd for
C6H6O5: C, 45.57; H, 3.80. Found: C, 45.49; H, 3.86.
4-Acetoxy-3-hydroxy-2-methoxycarbonyl-4-methyl-2-
pentenoate (9). 78% Yield. IR (KBr): 1743/1739/1735/
1732/1728/1724 (C=O) cm–1. 1H NMR (300 MHz, CDCl3):
= 1.58 (s, 6 H, 2 CH3), 2.05/2.06 (two s, 3 H, OCOCH3),
3.77 (s, 6 H, 2 COOCH3), 4.96 (s, 0.5 H, O=C-CH), 13.38
(s, 0.5 H, OH) ppm. 13C NMR (75 MHz, CDCl3): = 23.2
(CH3), 24.4 (CH3), 41.1 (O=C-CH), 53.2 (COOCH3), 59.5
(OCOCH3), 77.8 (C-4), 84.7 (C-2), 164.5 (OCOCH3), 170.1
(C-1), 197.7 (C-3) ppm.
3-Methoxycarbonyl-5-phenyl Tetronic Acid (15). 81%
Yield, mp: 188–189 °C. [ ]D21: +86.6 (c1, MeOH). IR
(KBr): 1759/1716 (C=O), 1610 (C=C) cm–1. 1H NMR (300
MHz, CDCl3): = 3.97 (s, 3 H, COOCH3), 5.84 (s, 1 H,
HCPh), 7.39–7.44 (m, 5 H, PhH) ppm. 13C NMR (75 MHz,
CDCl3): (ppm) 52.7 (COOCH3), 78.6 (C-5), 94.2 (C-3),
126.5/129.2/130.0/132.3 (phenyl carbons), 166.3 (C-6),
166.9 (C-2), 190.3 (C-4). Anal. Calcd for C12H10O5: C,
61.54; H, 4.27. Found: C, 61.60; H, 4.21.
Acknowledgement
We thank Ms. V. Skouridou (National Technical University of
Athens, Biotechnology Laboratory) for recording the IR spectra,
Mr. C. Makedonas and Mr. A. Grigoropoulos (University of
Athens, Laboratory of Inorganic Chemistry) for recording a part of
the NMR spectra.
References
(1) Pattenden, G. Fortschr. Chem. Org. Naturst. 1978, 35, 133.
(2) Booth, P. M.; Fox, C. M. J.; Ley, S. V. J. Chem. Soc., Perkin
Trans 1 1987, 121.
(3) Mittra, A.; Yamashita, M.; Kawasaki, I.; Murai, H.;
Yoshioka, T.; Ohta, S. Synlett 1997, 909.
(4) Bourguet-Kondracki, M.-L.; Guyot, M. Tetrahedron Lett.
1999, 40, 3149.
(5) Holler, U.; Konig, G. M.; Wright, A. D. J. Nat. Prod. 1997,
60, 832.
(6) Clutterbuck, P. W.; Raistrick, H.; Reuter, F. Biochem. J.
1935, 29, 300.
(7) Birkinshaw, J. H.; Samant, M. S. Biochem. J. 1960, 74, 369.
(8) Watanabe, K.; Tanaka, T.; Fukuhara, K.; Miyairi, N.;
Yonehara, H.; Umezawa, H. J. Antibiot. 1957, 10, 39.
(9) Jones, R. C. F.; Duller, K. A. M.; Vulto, S. I. E. J. Chem.
Soc., Perkin Trans. 1 1998, 411.
(10) Schobert, R.; Muller, S.; Bestmann, H.-J. Synlett 1995, 425.
(11) (a) Effenberger, F.; Syed, J. Tetrahedron: Asymmetry 1998,
9, 817. (b) Buhler, H.; Bayer, A.; Effenberger, F. Chem.–
Eur. J. 2000, 6, 2564.
(12) Mitsos, C. A.; Zografos, A. L.; Igglessi-Markopoulou, O.
J. Org. Chem. 2000, 65, 5852.
(13) Athanasellis, G.; Gavrielatos, E.; Igglessi-Markopoulou, O.
Synlett 2001, 1653.
3-Ethoxycarbonyl-5-phenyl Tetronic Acid (16). 80%
Yield, mp: 156–157 °C. [ ]D21: +71.1 (c1, MeOH). IR
(KBr): 1758/1714 (C=O), 1607 (C=C) cm–1. 1H NMR (300
MHz, CDCl3): = 1.41 (t, J = 7.5 Hz, 3 H, COOCH2CH3),
4.43 (q, J = 6.6 Hz, 2 H, COOCH2CH3), 5.83 (s, 1 H, HCPh),
7.39–7.44 (m, 5 H, PhH) ppm. 13C NMR (75 MHz, CDCl3):
= 14.0 (COOCH2CH3), 62.2 (COOCH2CH3), 78.5 (C-5),
94.2 (C-3), 126.5/129.2/129.9/132.4/(phenyl carbons),
166.3 (C-6), 166.6 (C-2), 190.3 (C-4) ppm. Anal. Calcd for
C13H12O5: C, 62.90; H, 4.84. Found: C, 62.98; H, 4.94.
3-Methoxycarbonyl-5-dimethyl Tetronic Acid (17). 50%
Yield, mp: 118–120 °C. IR (KBr): 1748/1721 (C=O), 1625
(C=C) cm–1. 1H NMR (300 MHz, CDCl3): = 1.56 (s, 6 H,
(14) Athanasellis, G.; Gavrielatos, E.; Igglessi-Markopoulou, O.
Bull. Chem. Soc. Jpn. 2002, in press.
(15) General Procedure for the Synthesis of Compounds
4–21:
2
CH3), 3.78/3.94 (two s, 3 H, COOCH3) ppm. 13C NMR
In a typical reaction, 10 mmol of the appropriate O-acetyl
hydroxy acid 1a–e was treated with 10 mmol of 1-
hydroxybenzotriazole 2 and 10 mmol DCC in anhyd THF
(40 mL) at 0 °C for 1 h. The resulting suspension was
refrigerated overnight at 3–5 °C. The precipitated solid
(DCCU) was filtered off and discarded, the THF filtrate was
added to a solution of 20 mmol NaH and 10 mmol of
dimethyl malonate 3a, diethyl malonate 3b or butyryl acetate
3c in anhyd THF. The resulting mixture was stirred at r.t. for
2.5 h and then concd in vacuo. The obtained gummy solid
(75 MHz, CDCl3): = 23.6 (CH3), 52.6 (COOCH3), 80.9
(C-5), 99.9 (C-3), 165.5 (C-6), 167.0 (C-2), 194.6 (C-4)
ppm. Anal. Calcd for C8H10O5: C, 51.61; H, 5.38. Found: C,
51.79; H, 5.48.
(17) Nolte, M. J.; Steyn, P. S.; Wessels, P. L. J. Chem. Soc.,
Perkin Trans. 1 1980, 1057.
(18) Petroliagi, M.; Igglessi-Markopoulou, O. J. Chem. Soc.,
Perkin Trans. 1 1997, 3543.
Synlett 2002, No. 10, 1736–1738 ISSN 0936-5214 © Thieme Stuttgart · New York