References
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For reviews covering 3-acyl tetramic
acid natural products, see:
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1a
Royles BJL.
Chem. Rev.
1995,
95:
1981
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1b
Rosen T.
Drugs
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Singh SB.
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Goetz MA.
Dombrowski AW.
Polishook JD.
Hazuda DJ.
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1998,
39:
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3a
Sugie Y.
Dekker KA.
Inagaki T.
Kim Y.-J.
Sakakibara T.
Sakemi S.
Sugiura A.
Brennan L.
Duignan J.
Sutcliffe JA.
Kojima Y.
J. Antibiot.
2002,
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3b
Singh MP.
Zaccardi J.
Greenstein M.
J. Antibiot.
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51:
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3c
Vesonder RF.
Tjarks LW.
Rohwedder WK.
Burmeister HR.
Laugal JA.
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3d
Burmeister HR.
Bennett GA.
Vesonder RF.
Hesseltine CW.
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Sugie Y.
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Kato Y.
Nishida H.
Pang C.-H.
Saito T.
Sakemi S.
Dib-Hajj F.
Mueller JP.
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- 5 For a review, see: Economou A.
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1
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aldehyde 4 (R = H),
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Yuki K.
Shindo M.
Shishido K.
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6b
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Jones RCF.
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Jones RCF.
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Of the members of this class of
natural products only equisetin(1a) has
been synthesized so far. For the three total syntheses, which all
feature a final Lacey-Dieckmann cyclisation for the construction
of the 3-acyl tetramic acid moiety, see:
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8a
Ref.
[6a]
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8b
Burke LT.
Dixon DJ.
Ley SV.
Rodriguez F.
Org.
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2000,
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3611
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8c
Ref.
[6b]
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For 5-monoalkylations and 5,5-dialkylations
as well as for5-hydroxyalkylations of 5-unsubstituted
4-O-methyl tetramates, see:
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9a
Gill GB.
James GD.
Oates KV.
Pattenden G.
J.
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9b
Ref.
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9c
Ref.
[7b]
- 10 For a recent asymmetric approach
to 5-hyroxymethyl-5-methoxycarbonyl tetramic acids, see: Andrews MD.
Brewster AG.
Crapnell KM.
Ibbett AJ.
Jones T.
Moloney MG.
Prout K.
Watkin D.
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Paintner FF.
Metz M.
Bauschke G.
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Mander LN.
Sethi SP.
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5425
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Bianco A.
Passacantilli P.
Righi G.
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Sakaitani M.
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12 Compund 5b was
obtained in 96% yield from commercially available 4-benzyloxy-1,5-dihydropyrrol-2-one
by acylation with di-tert-butyl dicarbonate
(2.0 equiv) in the presence of Et3N (1.0 equiv) and DMAP
(1.0 equiv) (CH2Cl2, r.t.).
14
Typical Procedure: A
solution of n-BuLi (1.6 M in hexane, 3.75
mL, 6.0 mmol) was added dropwise to a stirred solution of 5a (1.219 g, 6.0 mmol) in THF (60 mL) at -78 °C.
After stirring for 1 h at -78 °C, methyl
chloroformate (232 µL, 3.0 mmol) was added and the mixture
was stirred for 3 h at
-78 °C.
A 2.5% aq KH2PO4 solution (60 mL)
was added, the resulting mixture was allowed to warm to r.t. and
was extracted with CH2Cl2 (3 ¥ 100
mL). The combined organic layers were dried (MgSO4) and
evaporated under reduced pressure. The resulting residue was purified
by flash chromatography (n-hexane-EtOAc,
20:80) to give 6a (752 mg, 96%).
Methyl 3-benzyloxy-1-methyl-5-oxo-2,5-dihydro-1
H
-pyrrole-2-carboxylate
(
6a): Colorless crystals. Mp 104 °C. 1H
NMR (500 MHz, CDCl3): δ = 2.91
(s, 3 H, NCH3), 3.81 (s, 3 H, OCH3), 4.58
(s, 1 H, 2-H), 5.01 (s, 2 H, CH2Ph), 5.17 (s, 1 H, 4-H),
7.33-7.38 (m, 5 H, Harom). IR(film): ν = 1747, 1692,
1631 cm-1. MS (CI, CH4): m/z (%) = 262(100) [M + H+].
Anal. Calcd for C14H15NO4 (261.3):
C, 64.36; H, 5.79; N, 5.36. Found: C, 64.27; H, 5.77; N, 5.34.
15
Typical Procedure:
A solution of 6a (653 mg, 2.5 mmol) in THF
(35 mL) was added dropwise to a solution of LHMDS (1.0 M in THF,
2.63 mL, 2.63 mmol) in THF (40 mL) at -78 °C.
After stirring for 1 h at -78 °C, CH3I
(779 µL, 12.5 mmol) was added and the mixture was allowed
to warm to r.t. and stirred for 16 h. A 2.5% aq KH2PO4 solution
(50 mL) was added and the mixture was extracted with CH2Cl2 (3 ¥ 100
mL). The combined organic layers were dried (MgSO4) and
evaporated under reduced pressure. The resulting residue was purified
by flash chromatography (n-hexane-i-PrOH, 70:30) to give 9a (647
mg, 94%).
Methyl 3-benzyloxy-1,2-dimethyl-5-oxo-2,5-dihydro-1
H
-pyrrole-2-carboxylate
(9a): Colorless crystals. Mp 95 °C. 1H
NMR (500 MHz, CDCl3): δ = 1.60
(s, 3 H, CH3), 2.81 (s, 3 H, NCH3), 3.73 (s,
3 H, OCH3), 4.99 (d, 1 H, J = 12.0
Hz, CH2Ph), 5.03 (d, 1 H, J = 12.0
Hz, CH2Ph), 5.12 (s, 1 H, 4-H), 7.31-7.40 (m,
5 H, Harom). IR(film): ν = 1739,
1682, 1631 cm-1. MS (CI, CH4): m/z (%) = 276(100) [M + H+]. Anal.
Calcd for C15H17NO4 (275.3): C,
65.44; H, 6.22; N, 5.09. Found: C, 65.51; H, 6.37; N, 5.03.
16 In case of lithium dienolate 8a, aggregation was indicated by the formation
of a colorless precipitate, which gradually dissolved in the course
of the alkylation reactions.