Cascade assembly of N,N' -dialkylbarbituric acids and aldehydes: A simple and efficient one-pot approach to the substituted 1,5-dihydro-2H,2'H- spiro(furo[2,3-d]pyrimidine-6,5'-pyrimidine)-2,2',4,4',6'(1'H,3H,3'H)-pentone framework

Article abstract of DOI:10.1016/j.tetlet.2010.10.041

Cascade assembly of N,N′-dialkylbarbituric acids and aldehydes in the presence of bromine leads to the selective and efficient formation of substituted 1,5-dihydro-2H,2′H-spiro(furo[2,3-d]pyrimidine-6,5′- pyrimidine)-2,2′,4,4′,6′-(1′H,3H,3′H)-pentones in

Full text of DOI:10.1016/j.tetlet.2010.10.041

Tetrahedron Letters 51 (2010) 6598–6601
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Cascade assembly of N,N0-dialkylbarbituric acids and aldehydes: a simple
and efficient one-pot approach to the substituted 1,5-dihydro-2H,20H-spiro-
(furo[2,3-d]pyrimidine-6,50-pyrimidine)-2,20,4,40,60(10H,3H,30H)-pentone
framework
⇑
Michail N. Elinson , Anatolii N. Vereshchagin, Nikita O. Stepanov, Pavel A. Belyakov, Gennady I. Nikishin
N. D. Zelinsky Institute of Organic Chemistry, Leninsky prospect 47, 119991 Moscow, Russia
a r t i c l e i n f o
a b s t r a c t
Cascade assembly of N,N0-dialkylbarbituric acids and aldehydes in the presence of bromine leads to the
selective and efficient formation of substituted 1,5-dihydro-2H,20H-spiro(furo[2,3-d]pyrimidine-6,50-
pyrimidine)-2,20,4,40,60-(10H,3H,30H)-pentones in 70–88% yields via a complex cascade process. Spirobar-
biturates containing the furo[2,3-d]pyrimidine framework are a class of compounds with interesting
pharmacological and physiological activity.
Article history:
Received 25 May 2010
Revised 28 September 2010
Accepted 8 October 2010
Available online 16 October 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Aldehydes
Barbituric acids
2,3-Dihydrofuran formation
Furo[2,3-d]pyrimidine
The discovery of novel synthetic methodologies to facilitate the
preparation of compound libraries is a pivotal focal point of re-
search activity in the field of modern medicinal and combinatorial
chemistry.1 Molecular complexity and diversity in natural and bio-
logically relevant systems encourage chemists to investigate new
methods and reactions.
One powerful approach towards this goal is to combine two or
more distinct reactions into a single transformation, thereby pro-
ducing cascade reactions as a sequential process. Cascade reactions
have been utilized to introduce molecular complexity from readily
available starting materials by combining two or more reactions
into a single transformation.2 As such, cascade reactions are of
increasing importance in modern organic chemistry. This is not
only due to the need for more efficient and less labour-intense
methods, but also a consequence of the increasing importance of
environmental considerations in chemistry.
in use.5 The current interest in barbiturates arises from their phar-
macological potential as analeptics, immunomodulating, anti-AIDS
and anticancer agents.6
Among 2,4,6(1H,3H,5H)-pyrimidinetriones, spirobarbiturates
are a class of compounds with interesting pharmacological and
physiological activity.7 The spirobarbiturate system incorporates
a spiro-connected hexahydropyrimidine-2,4,6-trione heterocyclic
ring and may be promising with respect to biological responses.
During the course of our studies on cascade and multicompo-
nent reactions we suggested a new strategy to cyclopropanes by
chemical and electrocatalytic construction of substituted cyclopro-
pane rings8 from CH-acids,9 activated olefins and CH-acids10 and
carbonyl compounds and CH-acids.11
Recently, we reported the first example of the cascade assembly
of a spirocyclopropane structure via direct transformation of
benzylidenemalononitriles and N,N0-dialkylbarbituric acids into
substituted 2-aryl-4,6,8-trioxo-5,7-diazaspiro[2.5]octane-1,1-di-
carbonitriles12 (Scheme 1).
Continued investigations in this area resulted in a cascade pro-
cess, namely direct cascade transformation of aromatic aldehydes
1a–j and N,N0-dialkylbarbituric acids 2a,b into spiro(furo[2,3-
d]pyrimidine-6,50-pyrimidine)pentones 3a–m (Scheme 2, Table 1).
Under the conditions of method A (bromine as the active halo-
gen compound, 1.2 equivalents of EtONa as base, and ethanol as
solvent) aldehydes 1a–j and N,N0-dialkylbarbituric acids 2a,b were
transformed into the corresponding substituted spiro(furo[2,3-
d]pyrimidine-6,50-pyrimidine)pentones 3a–m in 75–88% yields
2,4,6(1H,3H,5H)-Pyrimidinetriones are
a type of privileged
medicinal scaffold also known as barbiturates (derivatives of barbi-
turic acid), are well-known class of drugs that act as central ner-
vous system depressants and by virtue of this they produce a
wide spectrum of effects, from mild sedation to anaesthesia.3 They
are also effective as anxiolytics and as anticonvulsants.3a,4 Pheno-
barbital is the most widely used anticonvulsant and the oldest still
⇑
Corresponding author. Tel.: +7 499 137 38 42; fax +7 499 135 53 28.
E-mail address: elinson@ioc.ac.ru (M.N. Elinson).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.10.041

M. N. Elinson et al. / Tetrahedron Letters 51 (2010) 6598–6601
6599
R1
O
O
R2
R1
N
N
O
CN
Br2
+
O
NC
NC
R2
O
EtONa/ EtOH
N
CN
R2
O
N
R2
Scheme 1.
O
O
R2
O
O
R2
R1
O
R2
N
N
N
O
O
R2
Method A or B
N
+
+
O
O
N
N
O
R2
R2
N
O
O
N
R2
1a-j
2a,b
a R2 = Me; b R2 = Et
O
R2
a R1 = H, b R1 = 4-Me, c R1 = 4-t-Bu,
d R1 = 2-MeO, e R1 = 4-MeO,
f R1 = 2-Cl, g R1 = 3-Cl, h R1 = 4-Cl,
i R1 = 3-Br, j R1 = 4-NO2
3a-m
Method A: 1. EtONa / EtOH; 2. Br2, 3 h, r.t.
Method B: 1. EtOH; 2. 0.2 M Br2 in H2O, 1 h, 40 oC
Scheme 2.
Table 1
Cascade one-pot transformation of aldehydes 1a–j and N,N0-dialkylbarbituric acids 2a,b into spiro(furo[2,3-d]pyrimidine-6,50-pyrimidine)pentones 3a–ma,14
Entry
Aldehyde
Barbituric acid
R1
R2
Product, method, yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
1a
1b
1c
1d
1e
1f
1g
1h
1i
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
3a, A (88); B (83)
3b, A (86); B (81)
3c, A (85); B (78)
3d, A (77); B (69)
3e, A (82); B (70)
3f, A (85); B (79)
3g, A (88); B (81)
3h, A (82); B (73)
3i, A (86); B (80)
3j, A (79); B (75)
3k, A (75); B (68)
3l, A (82); B (74)
3m, A (85); B (79)
4-Me
4-t-Bu
2-MeO
4-MeO
2-Cl
3-Cl
4-Cl
3-Br
4-NO2
H
1j
1a
1b
1j
4-Me
4-NO2
Et
Et
a
Method A: 10 mmol of aldehyde 1, 20 mmol of N,N0-dialkylbarbituric acid 2, 10 mmol of bromine, 12 mmol of EtONa, 20 mL of EtOH, 3 h. Method B: 10 mmol of aldehyde
1, 20 mmol of N,N0-dialkylbarbituric acid 2, 10 mmol of bromine in 50 mL of H2O, 20 mL of EtOH, 40 °C, 1 h.
b
Isolated yield (isolation by filtration of the reaction mixture).
(Table 1). Method A was earlier used for the direct transformation
of benzylidenemalononitriles and N,N0-dialkylbarbituric acids
into substituted 2-aryl-4,6,8-trioxo-5,7-diazaspiro[2.5]octane-1,1-
dicarbonitriles12 (Scheme 1).
Based on the above results and the mechanistic data on the cas-
cade transformation of alkylidenemalononitriles and malononitrile
into tetracyano-substituted cyclopropanes,15 the cascade transfor-
mation of benzylidenemalononitriles and N,N0-dialkylbarbituric
acids into substituted 2-aryl-4,6,8-trioxo-5,7-diazaspiro[2.5]-
octane-1,1-dicarbonitriles12 and the direct cascade conversion of
carbonyl compounds and malononitrile into substituted tetracy-
anocyclopropanes,16 the following mechanism for the transforma-
tion of aldehydes 1a–j and barbituric acids 2a,b into the
spiro(furo[2,3-d]pyrimidine-6,50-pyrimidine)pentones 3a–m in
the presence of EtONa is proposed (Method A, Scheme 3).
Recently, we developed new conditions avoiding the use of a
base for the cascade synthesis of tetracyanocyclopropanes from
benzylidenemalononitriles and malononitrile.13 This process was
accomplished by the direct action of bromine as shown in Method
B, Scheme 2. Thus, the next step of our research was investigation
of spiro(furo[2,3-d]pyrimidine-6,50-pyrimidine)pentones 3a–m
formation from aldehydes 1a–j and N,N0-dialkylbarbituric acids
2a,b by the direct action of bromine using Method B, (Table 1).
The yields of spiro(furo[2,3-d]pyrimidine-6,50-pyrimidine)pen-
tones 3a–m using Method B were generally slightly lower, in the
range of 68–83%.
In the first step benzylidenebarbituric acid 4 is formed via
Knoevenagel condensation of aldehyde 1 and N,N0-dialkylbarbitu-
ric acid 2 in the presence of EtONa. Next, Michael addition of a sec-
ond N,N0-dialkylbarbituric acid 2 to the benzylidenebarbituric acid

6600
M. N. Elinson et al. / Tetrahedron Letters 51 (2010) 6598–6601
O
O
R2
N
O
O
O
R2
O
R1
N
R2
O
R1
R2
N
N
-
EtO
EtOH
N
O
+
O
-
EtO EtOH
,
O
N
R2
R2
4
1
2
R1
Br
R1
R1
O
O
O
O
O
O
Br
-
R2
O
R2
O
R2
O
R2
O
R2
R2
O
Br2
EtO
N
N
N
N
N
N
-
_Br
EtOH
-
_Br
N
N
N
N
O
N
N
O O
O O
O O
R2
R2
R2
R2
R2
R2
A
5
B
R1
O
O
R2
O
R2
N
N
N
O
O
O
N
R2
R2
3
Scheme 3.
O
O
O
R2
R1
R2
O
R1
N
N
O
+
O
EtOH
O
N
N
R2
R2
1
2
4
R2
O
R2
O
N
N
N
Br
O
Br2
+
O
N
R2
O
R2
O
2
6
R1
O
O
O
R2
O
O
R1
R2
N
N
R2
O
R2
N
N
+
Br
O
N
O
O
N
N
R2
O
O
O
N
R2
R2
R2
6
4
3
Scheme 4.

M. N. Elinson et al. / Tetrahedron Letters 51 (2010) 6598–6601
6601
10. (a) Elinson, M. N.; Feducovich, S. K.; Zakharenkov, A. A.; Bushuev, S. G.;
Pashchenko, D. V.; Nikishin, G. I. Mendeleev Commun. 1998, 15–17; (b) Elinson,
M. N.; Feducovich, S. K.; Starikova, Z. A.; Olessova, O. S.; Vereshchagin, A. N.;
Nikishin, G. I. Tetrahedron Lett. 2000, 41, 4937–4941; (c) Elinson, M. N.;
Feducovich, S. K.; Starikova, Z. A.; Vereshchagin, A. N.; Nikishin, G. I.
Tetrahedron Lett. 2005, 46, 6389–6393; (d) Elinson, M. N.; Feducovich, S. K.;
Starikova, Z. A.; Vereshchagin, A. N.; Belyakov, P. A.; Nikishin, G. I. Tetrahedron
2006, 62, 3989–3996.
11. (a) Elinson, M. N.; Feducovich, S. K.; Lizunova, T. L.; Nikishin, G. I. Tetrahedron
2000, 56, 3063–3069; (b) Elinson, M. N.; Feducovich, S. K.; Zaimovskaya, T. A.;
Vereshchagin, A. N.; Nikishin, G. I. Izv. Akad. Nauk Ser. Khim. 2005, 663–667; (c)
Vereshchagin, A. N.; Elinson, M. N.; Zaimovskaya, T. A.; Nikishin, G. I.
Tetrahedron 2008, 64, 9766–9770.
4 takes place in the presence of EtONa to give anion A. Bromina-
tion of anion A gives substituted 5-bromo-5-[aryl(2,4,6-trioxo-
hexahydropyrimidin-5-yl)methyl]pyrimidine-2,4,6(1H,3H,5H)-trione
5. Finally, cyclization of 5 into substituted 1,5-dihydro-2H,20H-spiro
(furo[2,3-d]pyrimidine-6,50-pyrimidine)-2,20,4,40,60-(10H,3H,30H)-pen-
tone 3 takes place in alcoholic solution (Scheme 3).
Of more interest was spiro(furo[2,3-d]pyrimidine-6,50-pyrimi-
dine)pentone 3 formation directly from aldehydes 1 and N,N0-dial-
kylbarbituric acids 2 via the direct action of bromine (Method B,
Scheme 4). In this case, rapid Knoevenagel condensation of alde-
hyde 1 with N,N0-dialkylbarbituric acid 2 takes place in the absence
of base, as was reported earlier,17 along with simultaneous bro-
mination of N,N0-dialkylbarbituric acid 2 to give bromobarbituric
acid 6. Then, addition of bromobarbituric acid 6 to benzylidenebar-
bituric acid 4 results in the formation of spiro(furo[2,3-d]pyrimi-
dine-6,50-pyrimidine)pentones 3 in a manner similar to that of
Method A (Scheme 4).
In summary, a new cascade assembly of barbituric acids and
aldehydes leading to the selective and efficient formation of
substituted 1,5-dihydro-2H,20H-spiro(furo[2,3-d]pyrimidine-6,50-
pyrimidine)-2,20,4,40,60-(10H,3H,30H)-pentones in 70–88% yields is
reported. The cascade process proceeds smoothly with aromatic
aldehydes bearing both electron-donating and electron-withdraw-
ing groups. This novel process offers a facile and convenient method
to prepare diversely substituted privileged spirobarbiturates, which
are a class of small-molecule ligands with different biomedical prop-
erties. The developed cascade procedures require simple and rea-
sonable starting materials. The reaction products are crystallized
directly from the reaction mixture. These novel types of cascade pro-
cesses bring us closer to the notion of ‘ideal synthesis’.18
12. Elinson, M. N.; Vereshchagin, A. N.; Stepanov, N. O.; Zaimovskaya, T. A.;
Merkulova, V. M.; Nikishin, G. I. Tetrahedron Lett. 2010, 51, 428–431.
13. Vereshchagin, A. N.; Elinson, M. N.; Stepanov, N. O.; Nikishin, G. I. Mendeleev
Commun. 2009, 19, 324–325.
14. General procedure. Method A: To an EtOH (10 mL) suspension of aromatic
aldehyde 1 (10 mmol) and barbituric acid 2 (20 mmol) in a 50 ml beaker,
NaOEt (12 mmol) in 10 mL of EtOH was added during 1 min. Next, Br2
(10 mmol) was added during 1 min without external cooling. The mixture was
stirred at room temperature for 3 h, the solid phase filtered, washed with H2O
and dried in a desiccator over P2O5 to give pure product 3. Method B: To an
EtOH (20 mL) solution of aromatic aldehyde 1 (10 mmol) and barbituric acid 2
(20 mmol) in a three-necked flask, was added bromine water (50 mL, 10 mmol,
0.2 M) during 5 min. The mixture was stirred at 40 °C for 1 h, the solid phase
filtered, washed with H2O and dried in a desiccator over P2O5 to give pure
product 3.
1,10,3,30-Tetramethyl-5-phenyl-1,5-dihydro-2H,20H-spiro(furo[2,3-d]pyrimidine-
6,50-pyrimidine)-2,20,4,40,60 (10H,3H,30H)-pentone (3a): white solid; mp 256–
258 °C; IR (KBr):
m = 1720, 1700, 1688, 1676, 1620, 1520, 1480, 1432, 1396,
1036 cmꢀ1; MS (70 eV, EI): m/z (%): 398 (71) [M+], 370 (10), 340 (7), 311 (44),
283 (16), 243 (100), 197 (36), 186 (20), 142 (57), 102 (52). Elemental Anal.
Calcd for C19H18N4O6 (398.4): C, 57.28; H, 4.55; N, 14.06. Found: C, 57.16; H,
4.61; N, 13.92. lH NMR (300 MHz, CDCl3): d = 2.40 (s, 3H, CH3), 3.12 (s, 3H, CH3),
3.22 (s, 3H, CH3), 3.40 (s, 3H, CH3), 5.11 (s, 1H, CH), 7.11–7.18 (m, 2H, Ph), 7.25–
7.35 (m, 3H, Ph); 13C NMR (75 MHz, CDCl3): d = 28.00, 28.19, 29.29, 29.77,
58.98, 85.30, 90.08, 128.05, 128.73, 129.28, 132.63, 149.41, 151.04, 158.45,
162.51, 162.82, 165.33.
5-(4-tert-Butylphenyl)-1,10,3,30-tetramethyl-1,5-dihydro-2H,20H-spiro(furo[2,3-
d]pyrimidine-6,50-pyrimidine)-2,20,4,40,60 (10H,3H,30H)-pentone (3c): white
Acknowledgements
solid; mp 228–230 °C; IR (KBr):
m = 1716, 1700, 1688, 1680, 1652, 1516,
1440, 1288, 1040 cmꢀ1; MS (70 eV, EI): m/z (%): 454 (3) [M+], 397 (1), 351 (6),
299 (7), 285 (2), 237 (5), 168 (4), 128 (8), 115 (20), 58 (100). Elemental Anal.
Calcd for C23H26N4O6 (454.5): C, 60.78; H, 5.77; N, 12.33. Found: C, 60.62; H,
5.93; N, 12.25. lH NMR (300 MHz, DMSO-d6): d = 1.25 (s, 9H, CH3), 2.33 (s, 3H,
CH3), 3.12 (s, 3H, CH3), 3.22 (s, 3H, CH3), 3.40 (s, 3H, CH3), 5.06 (s, 1H, CH), 7.05
(d, 3J(H,H) = 8.3 Hz, 2H, CH, Ar), 7.29 (d, 3J(H,H) = 8.3 Hz, 2H, CH, Ar); 13C NMR
(75 MHz, CDCl3): d = 27.15, 27.69, 28.97, 29.71, 31.00, 34.28, 56.00, 85.22,
90.26, 124.69, 128.31, 131.36, 150.01, 150.82, 151.01, 158.12, 162.28, 163.24,
165.53.
The authors acknowledge financial support from the Russian
Foundation for Basic Research (Project No. 09-03-00003).
References and notes
1. (a) Thompson, L. A. Curr. Opin. Chem. Biol. 2000, 4, 324–337; (b) Nefzi, A.;
Ostresh, J. M.; Houghten, R. A. Chem. Rev. 1997, 97, 449–472.
2. For reviews, see: (a) Tietze, L. F. Chem. Rev. 1996, 96, 115–136; (b) Padwa, A.
Pure Appl. Chem. 2003, 75, 47–62; (c) Nicolaou, K. C.; Edmonds, D. J.; Bulger, P.
G. Angew. Chem., Int. Ed. 2006, 45, 7134–7186.
3. (a) Brunton, L. L.; Lazo, J. S.; Keith, L. P. Goodman & Gilman’s the Pharmacological
Basis of Therapeutics, 11th ed.; The McGraw-Hill Companies, Inc.: New York,
2006; (b) Johns, M. W. Drugs 1975, 9, 448–478; (c) Whittle, S. R.; Turner, A. J.
Biochem. Pharmacol. 1982, 31, 2891–2895; (d) Chen, X.; Tanaka, K.; Yoneda, F.
Chem. Pharm. Bull. 1990, 38, 307–311; (e) Naguib, F. N. M.; Levesque, D. L.;
Wang, E.-C.; Panzica, P. P.; El Kouni, M. H. Biochem. Pharmacol. 1993, 46, 1273–
1278; (f) Bruner, H.; Ittner, K. P.; Lunz, D.; Schmatloch, S.; Schmidt, T.; Zabel, M.
Eur. J. Org. Chem. 2003, 855–862.
5-(2-Chlorophenyl)-1,10,3,30-tetramethyl-1,5-dihydro-2H,20H-spiro(furo[2,3-
d]pyrimidine-6,50-pyrimidine)-2,20,4,40,60 (10H,3H,30H)-pentone (3f): white
solid; mp 264–266 °C; IR (KBr):
m = 1712, 1696, 1688, 1676, 1516, 1440,
1384, 1300, 1188, 1036 cmꢀ1; MS (70 eV, EI): m/z (%): 397 (17) [M+ꢀCl], 340
(5), 283 (59), 226 (11), 176 (30), 136 (45), 113 (24), 75 (26), 66 (39), 58 (100).
Elemental Anal. Calcd for C19H17ClN4O6 (432.8): C, 52.73; H, 3.96; Cl, 8.19; N,
l
12.94. Found: C, 52.58; H, 4.09; Cl, 8.03; N, 12.83. H NMR (300 MHz, CDCl3):
d = 2.69 (s, 3H, CH3), 3.30 (s, 3H, CH3), 3.38 (s, 3H, CH3), 3.50 (s, 3H, CH3), 5.56
(s, 1H, CH), 7.10–7.18 (m, 1H, CH, Ar), 7.21–7.31 (m, 2H, CH, Ar), 7.33–7.41 (m,
1H, CH, Ar); 13C NMR (75 MHz, DMSO-d6): d = 27.68, 27.75, 28.72, 29.73, 52.57,
85.15, 88.93, 127.28, 129.02, 130.41, 131.36, 131.46, 132.92, 150.07, 150.85,
157.95, 162.63, 162.88, 165.48.
4. Lyons, K. E.; Pahwa, R. CNS Drugs 2008, 22, 1037–1045.
5. Sudha, S.; Lakshmana, M. K.; Pradhan, N. Pharmacol. Biochem. Behav. 1996, 54,
633–638.
1,10,3,30-Tetraethyl-5-(4-methylphenyl)-1,5-dihydro-2H,20H-spiro(furo[2,3-
d]pyrimidine-6,50-pyrimidine)-2,20,4,40,60 (10H,3H,30H)-pentone (3l): white
solid; mp 160–162 °C; IR (KBr):
m = 1712, 1688, 1676, 1656, 1504, 1440, 1408,
1380, 1312, 1228 cmꢀ1; MS (70 eV, EI): m/z (%): 468 (19) [M+], 353 (23), 298
(23), 285 (99), 211 (62), 170 (60), 142 (77), 115 (98), 70 (84), 44 (100).
Elemental Anal. Calcd for C24H28N4O6 (468.5): C, 61.53; H, 6.02; N, 11.96.
Found: C, 61.35; H, 5.95; N, 11.83. lH NMR (300 MHz, CDCl3): d = 0.69 (t,
3J(H,H) = 7.3 Hz, 3H, CH3), 1.20 (t, 3J(H,H) = 7.1 Hz, 3H, CH3), 1.35 (t,
3J(H,H) = 7.1 Hz, 3H, CH3), 1.44 (t, 3J(H,H) = 7.1 Hz, 3H, CH3), 2.31 (s, 3H, CH3),
3.02–3.18 (m, 1H), 3.28–3.44 (m, 1H), 3.88–4.20 (m, 6H), 4.85 (s, 1H, CH), 6.97
(d, 3J(H,H) = 8.1 Hz, 2H, CH, Ar), 7.12 (d, 3J(H,H) = 8.1 Hz, 2H, CH, Ar); 13C NMR
(75 MHz, CDCl3): d = 12.03, 12.81, 13.01, 13.53, 20.85, 36.39, 37.54, 37.87,
38.73, 58.59, 85.86, 89.49, 128.19, 129.30, 129.63, 139.04, 148.71, 150.16,
158.11, 162.07, 162.55, 165.27.
6. (a) Grams, F.; Brandstetter, H.; D’Alo, S.; Gepperd, D.; Krel, H. W.; Leinert, H.;
Livi, V.; Menta, E.; Oliva, A.; Zimmermann, G. Biol. Chem. 2001, 382, 1277–1285;
(b) Maquoi, E.; Sounni, N. E.; Devy, L.; Oliver, F.; Frankenne, F.; Krell, H. W.;
Grams, F.; Foidart, J. M.; Noel, A. Clin. Cancer Res. 2004, 10, 4038–4047; (c)
Uhlmann, C.; Froscher, W. CNS Neurosci. Ther. 2009, 15, 24–31.
7. (a) Mokrosz, J. L. Pharmazie 1985, 40, 359–360; (b) Prankerd, R. J.; McKeown, R.
H. Int. J. Pharm. 1992, 83, 39–45; (c) Galati, E. M.; Monforte, M. T.; Miceli, N.;
Raneri, E. Farmaco 2001, 56, 459–461; (d) Singh, P.; Paul, K. J. Heterocycl. Chem.
2006, 43, 607–612; (e) Dundee, J. W.; McIlroy, P. D. A. Anaesthesia 2007, 37,
726–734; (f) Lomlin, L.; Einsiedel, J.; Heinemann, F. W.; Meyer, K.; Gmeiner, P. J.
Org. Chem. 2008, 73, 3608–3611.
8. Elinson, M. N.; Feducovich, S. K.; Lizunova, T. L.; Nikishin, G. I. Elektrokhimiya
1996, 32, 42–52.
15. Elinson, M. N.; Feducovich, S. K.; Stepanov, N. O.; Vereshchagin, A. N.; Nikishin,
G. I. Tetrahedron 2008, 64, 708–713.
16. Elinson, M. N.; Vereshchagin, A. N.; Stepanov, N. O.; Ilovaisky, A. I.; Vorontsov,
A. Y.; Nikishin, G. I. Tetrahedron 2009, 65, 6057–6062.
17. Ded, M. L.; Bhuyan, P. J. Tetrahedron Lett. 2005, 46, 6453–6466.
18. ‘Towards the ideal synthesis’: Wender, P. A.; Handy, S. T.; Wright, D. L. Chem.
Ind. 1997, 765–769.
9. (a) Nikishin, G. I.; Elinson, M. N.; Feducovich, S. K. Izv. Akad. Nauk Ser. Khim.
1986, 1919–1920; (b) Elinson, M. N.; Lizunova, T. L.; Dekaprilevich, M. O.;
Struchkov, Y. T.; Nikishin, G. I. Mendeleev Commun. 1993, 192–193; (c)
Feducovich, S. K.; Elinson, M. N.; Nikishin, G. I. Izv. Akad. Nauk Ser. Khim.
1994, 1835–1836.