A. Ben Salem, J.-B. Regnouf-de-Vains / Tetrahedron Letters 42 (2001) 7033–7036
7035
appear as a perfect suit of resonance signals: a dedou-
10. (a) Molard, Y.; Bureau, C.; Parrot-Lopez, H.; Lamartine,
R.; Regnouf-de-Vains, J.-B. Tetrahedron Lett. 1999, 40,
6383–6387; (b) Molard, Y., Th e` se d’Universit e´ , Univer-
sit e´ Claude Bernard Lyon I, December, 2000.
bled doublet at 5.52 ppm (J =6.5 Hz, J =3.8 Hz), a
1
2
doublet at 5.59 ppm (J=3.8 Hz) and a doublet at
0.19 ppm (J=6.7 Hz), respectively. The methylene
1
−
4
protons of the pivaloyl groups appear as a well-defined
AB system (JAB=5.3 Hz) at 5.77, 5.83 ppm, their
non-equivalence probably resulting from their chiral
and hindered environment. Finally, the four carbonyl
11. Compound 2: A suspension of diacid 1 (0.206 g, 2.7 10
−
4
mol), N-hydroxysuccinimide (0.068 g, 5.92 10 mol) and
−
4
dicyclohexylcarbodiimide (0.122 g, 5.92 10 mol) in
ethyl acetate (40 ml) was stirred at 25°C under argon for
48 h. The precipitated urea was filtered off and the
1
13
resonance signals were assigned by H, C HMBC
experiment (Fig. 1).
filtrate was evaporated to dryness to give 2 as a white
1
powder (0.22 g; 85%). H NMR (CDCl ): 0.93 (s, 18H,
3
The penicillinic podand 4 described here is representa-
tive of a new kind of potentially therapeutically active
calixarene derivatives; for this reason, its antibiotic
activity as well as the synthesis of its mono-, tri- and
tetra-substituted analogues are under current investi-
gation.
2
3
2
4
Me C); 1.31 (s, 18H, 2Me C); 2.88 (s, 8H, 2CH CH );
3 3 2 2
.39, 4.39 (AB, JAB=13.4, 8H, Ar-CH -Ar); 5.21 (s, 4H,
2
OCH ); 6.59 (s, 2H, 2 OH); 6.74 (s, 4H, ArH); 7.08 (s,
2
H, ArH). Identical to Ref. 10. Compound 3: N,N-diso-
−3
propylethylamine (0.61 ml, 3.5×10 mol) was added to a
suspension of 6-APA (0.55 g, 2.53×10 mol) in dry
−3
DMF (2.5 ml; dried and distilled over CaH at rt) and
2
the mixture was stirred at rt under argon for 30 min.
−
3
Chloromethyl pivalate (0.74 ml, 5×10 mol) was then
added and stirring was continued at 26–28°C for 4 h.
Ethyl acetate (20 ml) was added and the resulting precip-
Acknowledgements
itate was filtered off. The filtrate was washed with H O
The authors are grateful to the Minist e` re de la
Recherche et de l’Enseignement Sup e´ rieur and to the
Centre National de la Recherche Scientifique for finan-
cial support, as well as to the Minist e` re de l’Enseigne-
ment Sup e´ rieur de Tunisie for a doctoral fellowship to
A.B.S.
2
(3×5 ml), dried over MgSO
A pH-controlled addition of a solution of p-TsOH in
then concentrated to a half.
4
−
3
ethyl acetate (0.475 g, 2.5×10 mol, 4.5 ml) resulted in
the slow precipitation of POMAPATs, which was col-
1
lected as white crystals (0.5 g; 40%). H NMR: 1.05 (s,
9
3
1
H, Me C); 1.42 (s, 3H, CH ); 1.49 (s, 3H, CH ); 2.37 (s,
3 3 3
H, CH of Ts); 4.47 (s, 1H, H(2)); 4.98 (d, J=4.2 Hz,
3
H, H(5) or H(6)); 5.41 (d, J=4.2 Hz, 1H, H(6) or
References
H(5)); 5.75, 5.84 (AB, JAB=5.5, 2H, OCH O); 7.17 (d,
2
J=8, 2H, ArH); 7.79 (d, J=8.2, 2H, ArH). Identical to
literature. Compound 4: A solution of 3 (0.115 g, 2.29×
1
. (a) Gutsche, C. D. In Calixarenes; Monographs in
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−
4
−4
10
mol) and diisopropylethylamine (0.11 ml, 6.32×10
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2
−
4
activated ester 2 (0.1 g, 1.07×10 mol) in CH Cl (7 ml)
2
2
and the mixture was stirred at 25°C under argon for 16
−
5
h. A second portion of 3 (0.5 equiv.; 0.026 g, 0.52×10
(almost) unlimited possibilities; B o¨ hmer, V. Angew.
mol) was then added and stirring was continued for 4 h.
The solvent was evaporated to dryness without heating
and the resulting solid material was chromatographed
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(
SiO ; CH Cl :CH CN, 90:10) to give an analytical sam-
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2
3
. Harris, Stephen J. WO Patent 95-IE8 19950124, 1995.
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52°C. UV (CHCl ): 284 (6000). IR (KBr):1693 (CO
1
3
amide); 1759, 1792 (strong and sharp, CO lactam, CO
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1
esters). H NMR: 0.90 (s, 6H, CH3 of APA); 1.08 (s,
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1
8H, Me C); 1.22 (s, 18H, Me C of Piv.); 1.25 (s, 18H,
9
403164, 1984.
3
3
Me C); 1.38 (s, 6H, CH3 of APA); 3.33, 4.43 (AB,
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6
. Hulmes, D.; Coleman, A.; Aubert-Foucher, E. (CNRS,
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3
JAB=13 Hz, 4H, Ar-CH -Ar); 3.49, 4.11 (AB, JAB=14
2
Hz, 4H, Ar-CH -Ar); 4.18 (s, 2H, H(2) of APA); 4.24,
2
5
.17 (AB, JAB=14.7 Hz, 4H, OCH ); 5.52 dd, J =6.5
2 1
Hz, J =3.8 Hz, 2H, H(6) of APA); 5.59 (d, J=3.8 Hz,
7
3–86.
2
7
8
. D’Arcy Hart, P.; Armstrong, A. J.; Brodaty, E. Infect.
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2H, H(5) of APA); 5.77, 5.83 (AB, JAB=5.3 Hz, 4H,
OCH
H(5) of ArOCH
H(3) and H(5) of ArOH); 8.03 (s, 2H, OH); 10.19 (d,
O); 6.90, 6.99 (AB, JAB=2.9 Hz, 4H, H(3) and
2
-); 6.99, 7.05 (AB, JAB=2.9 Hz, 4H,
2
1
3
J=6.7 Hz, 2H, NH). C NMR (CDCl
27.30 (Me C piv.); 27.70, 29.78 (Me of APA); 31.41,
32.00 (Me C); 32.44, 33.38 (Ar-CH -Ar); 34.21, 34.54
; 400 MHz):
3
9
. Daehne, W.v.; Fredericksen, E.; Gundersen, E.; Lund,
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L.; Godtfredsen, W. O. J. Med. Chem. 1970, 13, 607–
3
3
2
(Me C); 39.20 (Me C piv.); 60.06 (C(6) of APA); 64.92
3
3
6
12.
(C(3) of APA); 69.05 (C(5) of APA); 70.81 (C(2) of