Syntheses of N-[3-(1-methyl-1H-2-imidazolyl)propyl]benzamides and N-[3-(1-methyl-1H-2-imidazolyl)propyl]benzenesulfonamides

Article abstract of DOI:10.1002/jhet.5570420542

A series of substituted N-(4-substituted-benzoyl)-N-[3-(1-methyl-1H- imidazol-2-yl)propyl]amines (13) and N-arylsulfonyl-N-[3-(1-methyl-1H-imidazol- 2-yl)propyl]amines (14) were prepared from the reaction of 3-(1-methyl-1H- imidazol-2-yl)propan-1-arnine (

Full text of DOI:10.1002/jhet.5570420542

Jul-Aug 2005
1011
Syntheses of N-[3-(1-Methyl-1H-2-imidazolyl)propyl]benzamides
and N-[3-(1-Methyl-1H-2-imidazolyl)propyl]benzenesulfonamides
A. Shafiee*, P. Shabani, M. Vosooghi, A. Foroumadi
Department of Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center,
Tehran 14174, Iran
Received January 13, 2005
A series of substituted N-(4-substituted-benzoyl)-N-[3-(1-methyl-1H-imidazol-2-yl)propyl]amines
(13) and N-arylsulfonyl-N-[3-(1-methyl-1H-imidazol-2-yl)propyl]amines (14) were prepared from the reac-
tion of 3-(1-methyl-1H-imidazol-2-yl)propan-1-amine (7) with substituted benzoyl chloride or substituted-
benzene sulfonyl chloride respectively. Compound 7 was prepared by two independent methods.
J. Heterocyclic Chem., 42, 1011 (2005).
Study of arachidonic acid cascade has led to the discov-
ery of thromboxane A (TXA ) [1] and prostacyclin
1-methylimidazole nucleus to give compounds III and IV
(Figure 1) respectively.
2
2
(PGI ) [2], which play important roles in the cardiovascu-
In the other hand, hypolipidemic and antibacterial activ-
ities of polyamides containing 1-methylimidazole-2-
propylamine have been reported [13-15]. Finally, it has
been shown that TXS is present in all stages of spermato-
genesis cells; spermatogonia, spermatocytes, spermatides,
and spermatozoa [16]. Thus, we would like to report the
synthesis of the title compounds as possible drugs effective
in fertility regulation [17,18].
Reaction of potassium phthalimide (1) with 4-bromo-
butyronitrile in dimethyl formamide gave 4-(1,3-dioxo-
1,3-dihydro-2H-isoindol-2-yl)butyronitrile (3) in 78%
yield [19]. Compound 3 was converted to [3-(1H-imida-
zol-2-yl)propyl]-1H-isoindole-1,3(2H)-dione (5) by a
known procedure [20].
Methylation of compound 5 with dimethyl sulfate or
dimethyl carbonate failed and did not give the desired
product 6. However, compound 6 was directly prepared
from the reaction of compound 4 with methylaminoac-
etaldehyde dimethylacetyal in methanol in 69% yield [21].
Hydrolysis of compound 6 with 5 M hydrochloric acid
[22] gave the desired compound, namely, 3-(1-methyl-1H-
imidazol-2-yl)propan-1-amine dihydrochloride [21] (7) in
62% yield (Scheme 1).
The second route for the preparation of compound 7
starts from the readily available 1-methyl-1H-imidazol-2-
carbadehyde (8) [23]. Condensation of ethyl cyanoacetate
with compound 8 gave ethyl 2-cyano-3-(1-methyl-1H-imi-
dazol-2-yl)acrylate (9) [24]. Hydrolysis and decarboxyla-
tion of compound 9 for the preparation of compound 10
failed. The alternative method for the preparation of com-
pound 10 could be through the intermediate 11. The latter
was prepared from the condensation of cyanoacetic acid
with aldehyde 8. Compound 11 was decarboxylated during
the work up to give compound 10. However, the yield of
this procedure (32%) was not satisfactory. Finally, com-
pound 10 could be prepared in good yield (75%) from the
Wittig reaction of diethyl cyanomethylphosphonate [25]
with aldehyde 8 [26,27].
2
lar system and the regulation of platelet function [3].
Agents that might selectively interfere with enzymes
might be potential drugs useful in the treatment of car-
diovascular disease. In particular, selective inhibition
without inhibiting PGI synthesis of TXA appears to
2
2
be an interesting target since TXA causes seemingly
2
adverse cardiovascular effects such as vasoconstriction
[4], platelet aggregation [3], atherosclerosis [5],
ischemia [6], and sudden death [7]. In addition, TXA
2
has been shown to be the most potent endogenous vaso-
constrictor known, it was hoped that some TX
inhibitors might have antihypertensive activity in cer-
tain forms of hypertension where in TX maintains
blood pressure [8]. Several laboratories have investi-
gated the selective inhibitors of thromboxane syn-
thetase (TXS) such as dazoxiben [9] (I), 4'-(1H-imida-
zol-1-yl)acetophenone [10] and 4-[(2-pyridylmethyl)-
amino]benzoic acid [11]. Also, the syntheses of N-[3-
(1H-imidazol-1-yl)propyl]benzamides (II) as TXS
inhibitor have been reported [8].
These agents were developed from an early observation
that imidazole was a selective (if not potent) inhibitor of
human platelet TXS [12]. Our approach to this problem
involved the attachment of highly polar but neutral moi-
eties such as aryl amides or aryl sulfonamides to

1012
A. Shafiee, P. Shabani, M. Vosooghi, A. Foroumadi
Vol. 42
Compound 10 was a mixture of cis and trans which was
The physicochemical data of compounds 13 and 14 are
summarized in Table 1.
separated by preparative tlc and characterized by NMR.
Direct reduction of compound 10 to compound 7 using
Raney nickel [28] or sodium borohydride-aluminium chlo-
ride in diglyme [29] failed and did not give compound 7.
However, compound 10 could be reduced to the desired
compound 7 in two steps. The double bond was reduced
with magnesium turning in methanol to give 3-(1-methyl-
1H-imidazol-2-yl)propionitrile 12. Usual method for
reduction of nitrile with lithium aluminum hydride for the
preparation of 7 failed [30-32]. However the nitrile could
be reduced by catalytic hydrogenation using Raney nickel
in methanol and ammonia [8].
EXPERIMENTAL
Melting points were determined on a Kofler hot stage appara-
tus and are uncorrected. The ir spectra were obtained using a
Perking-Elmer Model 781 or Nicollet FT-IR Magna 550 spectro-
1
graphs. The H-nmr spectra were obtained on a Bruker FT-80
spectrometer and chemical shifts (δ) are in ppm relative to inter-
nal tetramethylsilane. Mass spectra were obtained on a Finnigan
MAT TSQ 70 spectrometer at 70 eV. Silica gel HT-25 (E. Merck)
was used for thin-layer chromatography.
Ethyl 2-Cyano-3-(1-methyl-1H-imidazol-2-yl)acrylate (9).
Reaction of amine 7 with 4-substituted-benzoyl chloride
gave 4-substituted-N-[3-(1-methyl-1H-imidazol-2-
yl)propyl]benzamides (13). Similarly 4-substituted-N-[3-
(1-methyl-1H-imidazol-2-yl)propyl]benzene sulfonamides
(14) was prepared from the reaction of substituted-ben-
zenesulfonyl chloride with the amine 7 (Scheme 2).
To a stirred mixture of ethyl cyanoacetate (1.3 g, 0.01 mole) in
aqueous solution of sodium carbonate (1.06 g, 0.01 mole in 10
mL H O) compound 8 (1.1 g, 0.01 mole) was added. After 2
2
hours the mixture was extracted with chloroform (3x50 mL). The
solvent was evaporated and the residue was crystallized from
petroleum ether to give 1.38 g (76%) of 9; mp 142-145 °C; ir
-1
1
(KBr): ν 2220 (C≡N), 1715 cm (C=O); H-nmr (deuterio-

Jul-Aug 2005
Syntheses of N-[3-(1-Methyl-1H-2-imidazolyl)propyl]benzamides
1013
chloroform): δ 7.98 (s, 1H, CH= ), 7.48 (s, 1H, imidazole), 7.13
The slow moving fraction was crystallized from chloroform-
(s, 1H, imidazole), 4.39 (q, 2H, OCH ), 3.84 (s, 3H, NCH ), 1.39
petroleum ether to give cis isomer mp 92-93 °C; ir (KBr): ν
2
3
+
+
-1
1
(t, 3H, CH ); ms: m/z (%) 206 ( M +1, 100), 205 (M ,14), 161
2220 (C≡N), 1625 (C=C), 735 cm (CH cis); H-nmr (deuteri-
ochloroform): δ 7.05 (s, 1H, imidazole), 6.99 (s, 1H, imida-
zole), 6.94 (d, 1H, J=11.8 Hz), 5.42 (d, 1H, J=11.8 Hz), 3.72 (s,
3
(30), 132 (20), 107 (5).
Anal. Calcd. for C H N O : C, 58.54; H, 5. 37; N, 20. 49.
10 11
3 2
Found: C, 58.73; H, 5.19; N, 20.68.
3H, N-CH ).
3
3- (1-Methyl-1H-imidazol-2-yl)acrylonitrile (10).
Method B.
To a stirred solution of compound 8 (1.1 g, 0.01 mole) in
dry THF (5 mL) a solution of diethyl cyanomethyl phospho-
nate (1.78 g, 0.01 mole) in dry THF (5 mL), which was
treated with sodium hydride (240 mg, 0.01 mole) at ice-bath
temperature was added. After 30 minutes the solvent was
evaporated. The residue was crystallized from chloroform-
petroleum ether to give 1 g (75%) of compound 10 as a mix-
A stirred solution of compound 8 (0.2 g, 1.8 mmoles),
cyanoacetic acid (0.16 g, 1.8 mmoles), piperidine (0.16 g, 1.8
mmoles) and a few drops of acetic acid in toluene (20 mL) was
refluxed under Dean-Stark trap for 18 hours. The solvent was
evaporated under the reduced pressure. The residue was made
alkaline with aqueous 0.5% sodium hydroxide solution and
extracted with chloroform. The organic layer was evaporated
and the residue was crystallized from chloroform-petroleum
ether to give 80 mg (32%) of compound 10, mp 88-90°C.
Under the above condition compound 11 formed at first was
decarboxylated under the work up condition and compound 10
was formed as cis-trans mixture.
1
ture of cis and trans isomers; mp 88-90 °C. H-nmr (deuterio-
chloroform): δ 7.20 (d, trans CH=C-CN, J=15.9 Hz), 7.07 ( d,
cis, CH=C-CN, J=11.5 Hz), 6.95 (s, 1H, imidazole), 6.45 (s,
1H, imidazole), 6.84 (s, 1H, imidazole), 6.30 (d, trans,
C=CHCN, J=15.9 Hz), 5.45 (d, cis C=CH-CN, J=11.5 Hz),
+
3.73 (s, 3H, N-CH ); ms: m/z (%) 133 (M , 100), 107 (51), 79
3
3-(1-Methyl-1H-imidazol-2-yl)propanonitrile (12).
(21), 64 (20). The mixture (0.5 g) was separated by thin layer
chromatography (silica gel) using chloroform-ethanol (90:10)
as eluent. The fast moving fraction gave the trans isomer
which was crystallized from chloroform-petroleum ether mp
To a stirred solution of compound 10 (0.17 g, 1.31 mmoles) in
dry methanol (13 mL) at ice-bath temperature magnesium turning
(1.27 g, 53 mmoles) was added. Stirring was continued for 5 hours.
The excess magnesium was destroyed with 6 N hydrochloric acid
(24 mL). The pH of the solution was brought to 7-8 with sodium
bicarbonate, and extracted with chloroform. The organic layer was
dried (Na SO ) filtered and evaporated to give 0.16 g (92%) of 12
-1
95-96 °C; ir (KBr): ν 2220 (C≡N), 1630 (C=C), 900 cm (CH
1
trans); H-nmr (deuteriochloroform): δ 7.22 (d, 1H, J=15.9
Hz), 7.12 (s, 1H, imidazole), 7.03 (s, 1H, imidazole), 6.72 (d,
1H, J=15.9 Hz), 3.73 (s, 3H, N-CH ).
3
2
4

1014
A. Shafiee, P. Shabani, M. Vosooghi, A. Foroumadi
Vol. 42
Table 1
N
CH2CH2CH2NH
X
Ar
N
CH3
Comp.
X
Ar
mp°C [a]
yield
(%)
ir (KBr), 1H-nmr (CDCl3), ms and CHN
13a
CO
phenyl
128-129
89
ir: 3205 (NH), 1653 cm-1(C=O); 1H-nmr: 8.34 (bs, 1H, NH), 7.81 (m, 2H,
phenyl), 7.41 (m, 3H, phenyl), 6.94 (s, 1H, imidazole), 6.81 (s, 1H, imidazole),
3.57 (s, 3H, N-CH3), 3.58 ( t, 2H, CH2), 2.83 (t, 2H, CH2), 2.16 (m, 2H, CH2);
ms: m/z (%) 244 (M++1, 100), 108 (14), 105 (13), 95 (12), 77 (13). Anal. Calcd
for C14H17N3O: C, 69.14; H, 7.00, N, 17.28. Found: C, 6.36; H, 7.30; N, 17.49.
ir: 3201 (NH), 1644 cm-1(C=O); 1H-nmr: 8.84 (brs, 1H, NH), 7.75 (d, 2H,
J=8.4 Hz, phenyl), 7.54 (d, 2H, J=8.4 Hz, phenyl), 6.93 (s, 1H, imidazole),
6.82 (s, 1H, imidazole), 3.58 (s, 3H, N-CH3), 3.55 ( t, 2H, CH2), 2.84 (t, 2H,
CH2), 2.15 (m, 2H, CH2); ms: m/z (%) 323 (M++1, 100), 184 (5), 109 (39), 96
(18). Anal. Calcd for C14H16BrN3O: C, 52.17; H, 4.97, N, 13.04. Found: C,
52.02; H, 5.08; N, 13.22.
ir: 3270 (NH), 1631 cm-1(C=O); 1H-nmr: 8.11 (bs, 1H, NH), 7.71 (d, 2H,
J=8.4 Hz, phenyl), 7.18 (d, 2H, J=8.4 Hz, phenyl), 6.93 (s, 1H, imidazole),
6.79 (s, 1H, imidazole), 3.55 (s, 3H, N-CH3), 3.52 ( t, 2H, CH2), 2.80 (t, 2H,
CH2), 2.35 (s, 3H, CH3), 2.10 (m, 2H, CH2); ms: m/z (%) 258 (M++1, 99), 148
(5), 119 (40), 109 (100), 96 (60). Anal. Calcd for C15H19N3O: C, 70.04; H,
7.39, N, 16.34. Found: C, 69.86; H, 7.17; N, 16.15.
ir: 3231 (NH), 1659 cm-1(C=O); 1H-nmr: 8.11 (brs, 1H, NH), 7.76 (d, 2H,
J=8.0 Hz, phenyl), 7.32 (d, 2H, J=8.0 Hz, phenyl), 6.95 (s, 1H, imidazole),
6.81 (s, 1H, imidazole), 3.56 (s, 3H, N-CH3), 3.55 ( t, 2H, CH2), 2.82 (t, 2H,
CH2), 2.69 (q, 2H, CH2), 2.15 (m, 2H, CH2), 1.24 (t, 3H, CH3); ms: m/z (%)
272 (M++1, 76), 133 (40), 109 (100), 96 (70). Anal. Calcd for C16H21N3O: C,
70.85; H, 7.75, N, 15.50. Found: C, 70.67; H, 7.93; N, 15.72.
ir: 3100 (NH), 1321, 1163 cm-1(SO2); 1H-nmr: 7.81 (m, 2H, Phenyl), 7.50
(m, 3H, phenyl), 6.98 (bs, 1H, NH), 6.90 (s, 1H, imidazole), 6.74 (s, 1H,
imidazole), 3.51 (s, 3H, NCH3), 3.03 (t, 2H, CH2), 2.68 ( t, 2H, CH2), 1.94 (m,
2H, CH2); ms: m/z (%) 280 (M++1, 100), 138 (14), 109 (57), 95 (37). Anal.
Calcd for C13H17N3O2S: C, 55.91; H, 6.09, N, 15.05. Found: C, 56.15; H, 6.28;
N, 15.31.
ir: 3150 (NH), 1321, 1157 cm-1(SO2); 1H-nmr: 7.62 (d, 2H, J=8.8 Hz,
phenyl), 7.54 (d, 2H, J=8.8 Hz, phenyl), 6.86 (s, 1H, imidazole), 6.77 (s, 1H,
imidazole), 3.50 (s, 3H, NCH3), 2.98 (t, 2H, CH2), 2.67 ( t, 2H, CH2), 1.90 (m,
2H, CH2);ms: m/z (%) 359 (M++1, 100), 357 (98), 138 (18), 109 (93), 95 (37).
Anal. Calcd for C13H16BrN3O2S: C, 43.58; H, 4.47, N, 11.73. Found: C, 43.79;
H, 4.62; N, 11.51.
ir: 3155 (NH), 1311, 1163 cm-1(SO2); 1H-nmr: 7.68 (d, 2H, J=8.0 Hz,
phenyl), 7.25 (d, 2H, J=8.0 Hz, phenyl), 6.90 (s, 1H, imidazole), 6.83 (bs, 1H,
NH), 6.79 (s, 1H, imidazole), 3.51 (s, 3H, NCH3), 3.03 (t, 2H, CH2), 2.68 (t,
2H, CH2), 2.40 (s, 3H, CH3), 1.96 (m, 2H, CH2); ms: m/z (%): 294 (M++1,
100), 138 (58), 109 (94), 95 (46). Anal. Calcd for C14H19N3O2S: C, 57.34; H,
6.48, N, 14.33. Found: C, 57.11; H, 6.29; N, 14.12.
13b
13c
13d
14a
14b
14c
CO
CO
CO
SO2
SO2
SO2
4-bromophenyl
164-165
126-127
109-111
112-114
92-94
64
4-tolyl
85
75
80
69
72
4-ethylphenyl
phenyl
4-bromophenyl
4-tolyl
109-110
14d
SO2
4-chlorophenyl
100-101
69
ir: 3134 (NH), 1321, 1157 cm-1(SO2); 1H-nmr: 7.73 (d, 2H, J=8.4 Hz,
phenyl), 7.64 (bs, 1H, NH), 7.42 (d, 2H, J=8.4 Hz, phenyl), 6.92 (s, 1H,
imidazole), 6.81 (s, 1H, imidazole), 3.52 (s, 3H, NCH3), 3.06 (t, 2H, CH2), 2.68
( t, 2H, CH2), 1.96 (m, 2H, CH2), ms: m/z (%): 315 (M++1, 14), 313 (5), 279
(10), 109 (100), 95 (64). Anal. Calcd for C13H16ClN3O2S: C, 49.76; H, 5.10, N,
13.40. Found: C, 49.98; H, 5.26; N, 13.26.
[a] All compounds were crystallized from ethanol-ether.
-1
1
3-(1-Methyl-1H-imidazol-2-yl)propanamine (7).
as an oil; ir (KBr): ν 2260 cm (C≡N); H-nmr (deuteriochloro-
form): 6.88 (d, 1H, imidazole, J=0.8 Hz), 6.83 (d, 1H, imidazole,
J=0.8 Hz), 3.57 (s, 3H, NCH ), 2.93 (t, 2H, CH ), 2.83 (t, 2H,
A mixture of compound 12 (13.5 g, 0.1 mole), 25% aqueous
ammonium hydroxid solution 25%, (75 mL) and Raney nickel
alloy, was hydrogenated at 50 p.s.i. for 6 hours. The mixture was
3
2
.
+
CH ); ms: m/z (%) 135 (M , 47), 109 (8), 95 (100), 81 (5)
2

Jul-Aug 2005
Syntheses of N-[3-(1-Methyl-1H-2-imidazolyl)propyl]benzamides
1015
[6] B. Pitt, M. J. Shea, J. L. Romson and B. R. Lucchessi, Ann.
Int. Med., 99, 83 (1983).
[7] A. Myers, J. Penhos, E. Ramey and P. Ramwell, J.
Pharmacol. Exp. Ther., 224, 369 (1983).
[8] W. B. Wright , Jr., J. B. Press, P.S. Chan, J. W. Marsico, M. F.
Haug, J. Lucas, J. Tanber and A. S. Tomcufcik, J. Med. Chem., 29, 523
(1986).
[9] H. M. Tyler, C. A. P. D. Saxton and M. J. Parry, Lancet, 629
(1981).
filtered. The solvent was evaporated to give 12 g (86%) of 7 as an
oil which was converted to dihydrochloride salt with 5 M
1
hydrochloric acid mp 176-178 °C [ref. 21, mp 178° ]; H-nmr
(D O): δ 7.40 (s, 2H, imidazole), 3.90 (s, 3H, N-CH ), 3.15 (m,
2
3
4H, CH ), 2.15 (m, 2H, CH ).
2
2
Anal. Calcd. for C H Cl N : C, 39.62; H, 7.08; N, 19.81.
7
15
2 3
Found: C, 39.84; H, 7.29; N, 19.60.
.
[10] H. D. Underman, R. J. Workman and E. K. Jackson,
Prostaglandins, 24, 237 (1982).
[11] K. Anderegg, P. Anzeveno, J. A. Cook, P. V. Halushka, J.
McCarthy, E. Wagner and W. C. Wise, Br. J. Pharmacol., 78, 725 (1983).
[12] P. Needleman, A. Raz, J. A. Ferrendelli and M. Minkes Proc.
Natl. Acad. Sci. U.S.A., 74, 1716 (1977).
[13] N. Takahashi, K. Takeuchi, T. Abe, K. Murakami, M.
Yamaguchi and K. Abe, Endocrinology, 136, 4143 (1995).
[14] W. B. Caldwell, P. W. Erhardt, W. C. Lumma, Jr., G. B.
Phillips, K. J. Shaw, W. V. Taggart and B. R. Vennepalli, Eur. Pat.
389079 (1990); Chem. Abstr., 114, 199679d (1991).
[15] W. B. Caldwell, P. W. Erhardt, W. C. Lumma, Jr., G. B.
Phillips, K. J. Shaw, W. V. Taggert and B. R. Venepalli, Eur. Pat. 519119
(1992): Chem. Abstr., 119, 9391m (1993).
N-(4-Substituted-benzolyl)-N-[3-(1-methyl-1H-imidazol-2-yl)-
propyl]amine (13).
To a stirred of mixture compound 7 or its dihydrochloride salt
(2.6 mmoles) in dichloromethane (40 mL) 1 N aqueous sodium
hydroxide solution (30 mL) and 4-substituted-benzoyl chloride
(2.6 mmoles) in dichloromethane (16 mL) was added. The mixture
was stirred at room temperature for 2 hours. The organic layer was
washed with water, dried (Na SO ), filtered and evaporated. The
2
4
residue was chromatographed (silica gel, 230-400 mesh) using
CH Cl -MeOH (95:5) as eluent. The desired compound was crys-
2
2
tallized from CH Cl -ether to give compound 13. The physio-
2
2
chemical data of compounds 13a-13d are summarized in Table 1.
[16] K. R. Stevens and W. V. Taggart, U. S. Pat. 5516758 (1996);
Chem. Abstr., 125, 76423k (1996).
[17] M. Nazarinia, A. Sharifian and A. Shafiee, J. Heterocyclic
Chem., 32, 223 (1995).
[18] A. Shafiee, N. Rastkari and A. Foroumadi, J. Heterocyclic
Chem., 35, 607 (1998).
[19] A. F. Mckay, D. L. Garmaise, R. Gaudry, H. A. Baker, G. Y.
Paris, L. W. Kay, G. E Just and R. Schwartz, J. Am. Chem. Soc., 81, 4328
(1959).
[20] A. Bushanor and W. Schunach, J. Heterocyclic Chem., 21, 753
(1984)
[21] A. Buschauer, S. Postius, I. Szelenyi and W. Schunack,
Arzneim Forsch., 35, 1025 (1985).
N-Arylsulfonyl-N-[1-(1-methyl-1H-imidazol-2-yl)propyl]amine
(14).
To a stirred mixture of compound 7 or its dihydrochloride salt
(2 mmoles) in dichloromethane (30 mL) a saturated aqueous
sodium bicarbonate solution (20 mL) and 4-substituted-benzene-
sulfonyl chloride (3 mmoles) in dichloromethane (10 mL) were
added. The mixture was stirred at room temperature for 2 hours.
The organic layer was washed with water, dried (Na SO ), fil-
2
4
tered and evaporated. The residue was crystallized from ethanol-
ether to give compound 14. The physicochemical data of com-
pounds 14b-14d are summarized in Table 1.
[22] M. S. Gibson, R. W. Bradshaw, Angew Chem. Internat. Edit.,
7, 919 (1968).
Acknowledgement.
This work was supported by grants from the Research Council
of Tehran University of Medical Sciences and by Iran Chapter of
TWAS Based at ISMO.
[[23] P. Fournari, P. Cointet and E. Laviron, Bull. Soc. Chem. Fr., 6,
2438 (1968).
[24] M. Horfenist and A. P. Phillips, J. Am. Chem. Soc., 80, 6261
(1958).
[25] N. W. Dawson and A. Burger, J. Am. Chem. Soc., 74, 5312
(1952).
REFERENCES AND NOTES
[26] W. Gartner, D. Oesterbelt, E. Serfert-Schiller, P. Towner, H.
Hopf and I. Bohnn, J. Am. Chem. Soc., 106, 5654 (1984).
[27] N. Krause, H. Hopf and L. Ernst, Liebigs Ann. Chem., 1398
(1986).
[28] B. Startus and T Van Es, J. Chem. Soc., 531 (1966).
[29] H. C. Brown and B. C. Subba Rao, J. Am. Chem. Soc., 78,
2582 (1955).
[1] M. Hamberg, J. Svensson and B. Samuelsson, Proc. Natl.
Acad. Sci. U.S. A., 72 (1975).
[2] R. A. Johnson, D. R. Morton, , J. H. Kinner, R. R. Gorman, J.
C. McGuire, F.
F. Sun, N. Whittaker, S. Bunting, J. Salmon, S. Moncada and J. R. Van,
Prostaglandins, 12, 915 (1976).
[3] K. C. Nicolaou, Ann. Rep. Med. Chem., 14, 178 (1979).
[4] M. Humberg, J. Svensson and B. Samuelson, Proc. Natl.
Acad. Sci. U.S.A., 72, 2994 (1975).
[30] J. S. New, J. P. Yevich, Synthesis, 388 (1983).
[31] C. Sellior, A. Buschauer, S. Elz and W. Schunach, Liebigs
Ann. Chem., 317 (1992).
[5] J. J. Mehta, Am. Med. Assoc., 249, 2818 (1983).
[32] R. G. Jones J. Am. Chem. Soc., 71, 383 (1949).