Practical synthesis of active esters of 4-alkoxycarbonylamino-3- methoxypyrrole-2-carboxylic acid

Article abstract of DOI:10.1055/s-2000-6394

An efficient large scale synthesis of the HOAt active ester of 4-tert- butoxycarbonylamino-3-methoxypyrrole-2-carboxylic acid is reported.

Full text of DOI:10.1055/s-2000-6394

PAPER
673
Practical Synthesis of Active Esters of 4-Alkoxycarbonylamino-3-methoxy-
pyrrole-2-carboxylic Acid
Kesavaram Narkunan, Marco A. Ciufolini*
Université Claude Bernard Lyon 1 and Ecole Supérieure de Chimie, Physique, Electronique de Lyon, 43, Boulevard du 11 Novembre 1918,
69622 Villeurbanne cedex, France
Fax +33(4)72432963; E-mail: ciufi@cpe.fr
Received 6 October 1999; revised 5 January 2000
gram lots of 1. The presence of a free “phenolic” OH in 2
Abstract: An efficient large scale synthesis of the HOAt active es-
permits chemoselective base hydrolysis of the ester at po-
ter of 4-tert-butoxycarbonylamino-3-methoxypyrrole-2-carboxylic
acid is reported.
sition 4 to give acid 3. The Yamada modification7 of the
Curtius rearrangement of 3 produces isocyanate 4.8 At-
tempted reaction of 4 with t-BuOH gave a complex mix-
Key words: distamycin, DNA, pyrroles, Curtius rearrangement,
transesterifications, heterocycles
ture containing at best trace amounts of the desired Boc
product, even when capture of the isocyanate with
t-BuOH was attempted in the presence of catalysts such as
The possibility of achieving digital readout of DNA by
CuCl.9 In complete accord with Dervan,5 more reactive al-
chemical methods is becoming increasingly apparent
lyl alcohol did combine with the isocyanate to produce the
thanks especially to the work of Dervan and collabora-
corresponding allyl carbamate, but only in 30-40% yield.
A compound tentatively identified as 5 was also obtained
from this reaction, raising questions about the viability of
a free OH group during the Yamada step. Nonetheless,
tors.1 These workers have shown that analogs of the anti-
tumor agent, distamycin,2 are capable of sequence-
specific recognition of double-stranded DNA.3 The as-
sembly of such constructs requires quantities of various
production of the desired N-Boc intermediate in gram
heterocyclic building blocks,4 including active esters of
amounts became possible as shown in Scheme 1. The allyl
deceptively simple pyrroles of general structure 1
carbamate was O-methylated to furnish 6, which reacted
(R = alkyl, X = 1-benzotriazolyl or 1-pyridotriazolyl).5
The importance of 1 stems from its function as a recogni-
with Boc2O to give a mixed Alloc-Boc imide. Selective
Alloc cleavage under catalysis by Pd(0) then provided es-
tion element for thymine. Thus, unit 1 is incorporated into
ter 7. An even more troublesome difficulty emerged dur-
a pyrrolic polyamide and the C-3 “phenolic” OH is ulti-
ing hydrolysis of 7 in accord with the published
mately liberated. This hydroxyl group, together with the
procedure,5 which calls for prolonged (3 days) heating of
C-4 amido NH function, is believed to establish a bifur-
cate H-bond to the carbonyl group of thymine.5
R–OOC
OH
O=C=N
OH
ROOC–HN
OMe
O
DPPAb
Et3N
3
4
O–X
COOEt
COOEt
N
N
2
N
1
X = alkyl, 1-Bt
or 1-At
Me
Me
4
Me
2
3
R = Et
R = H
NaOHa
Alloc–HN
OMe
Whereas methods for the preparation of most of the fore-
going building blocks are described in the primary litera-
ture,4 the synthesis of compounds related to 1, on scales of
a few hundred milligrams, has been recorded only in a
patent.5,10 Ongoing research required quantities of an ac-
tive ester of 1, wherein the 4-amino group is blocked as an
N-Boc derivative. Such an intermediate has been claimed
in the above patent,5 but details of its preparation are not
provided.10
1. allyl alcoholc
1. Boc2Oe
COOEt
N
f
d
2. Pd(PPh3)4
2. Me2SO4
Me
6
Boc–HN
OMe
Boc–HN
OMe
NaOH
then H3O+
COOEt
R
N
N
7
Me
Me
Our first attempts to produce the desired goal proceeded
through modifications of the patented procedures, which
evolve from diethyl ester 2, readily available in 100 g
batches through a published, fully reproducible method.6
In our hands, modifications of public-domain protocols
were entirely unsatisfactory for the synthesis of multi-
8
9
R = COOH
R = H
Reagents and conditions: a) EtOH/H2O, 100°C, 6 h, 75%; b) MeCN,
85°C, 2 h; c) 100°C, 17 h, 40%; d) K2CO3/acetone, reflux, 24 h, 85%;
e) TEA/DMAP/THF, r.t., 16 h, 93%; f) dimedone/THF, r.t., 2 h, 80%
Scheme 1
Synthesis 2000, No. 5, 673–676 ISSN 0039-7881 © Thieme Stuttgart · New York

674
K. Narkunan, M. A. Ciufolini
PAPER
Compound 16 was not extensively characterized, due to
its propensity to undergo facile decarboxylation; rather, it
was immediately condensed with, e.g., HOAt in the pres-
ence of DCC and 4-DMAP to furnish active ester 1
(R = At) in high yield. Material of sufficient purity (NMR,
elemental analysis) for use in the synthesis of Dervan
polyamides was obtained after a simple precipitation from
a CH2Cl2 solution by addition of hexane.
O
NH
N
OH
H
O
O
N
E
O
N
E
Me
Me
5
the substrate at 100°C in strongly basic medium. We were
never able to obtain acid 8 in greater than 30-35% yield,
due to its very facile, and not unexpected, decarboxylation
to pyrrole 9. No simple solution to this problem could be
found.
In summary, a protocol for the synthesis of active esters of
1 on multigram scale is now available. The new procedure
should be a welcome improvement over published routes
to the target systems, on accounts of their importance in
nucleic acid, genomics and medicinal chemistry research.
Our observations suggest that an expressed pyrrolic OH
group is largely incompatible with the Curtius sequence,
even though its presence is required in order to achieve
chemoselective ester hydrolysis of 2. Moreover, the vig-
orous conditions applied to saponification of the C-2 ester
in 7 must be avoided. We thus researched a new protocol
for the synthesis of 1 (R = t-Bu, X = 1-At) on large scale.
A robust process was developed as shown in Scheme 2.
All sensitive reactions were carried out under argon. BnOH and al-
lyl alcohol were stored over anhyd K2CO3 before use. THF was
freshly distilled from Na/benzophenone. t-BuOH was freshly dis-
tilled from Na before use. MeCN, CH2Cl2 and TEA were freshly
distilled from CaH2. DPPA, dimethyl sulfate and K2CO3 (325 mesh)
were used as received. Unless otherwise indicated, NMR spectra (d,
ppm, 300 MHz for 1H; 75 MHz for 13C; 25°C, coupling constants J
in Hz) were recorded in CDCl3 with TMS as internal standard; FTIR
spectra (cm-1) were obtained from thin films on NaCl plates (oils)
or from KBr pellets (solids). Low and high resolution mass spectra
(m/z) were obtained in EI mode. Microanalyses were carried out at
the CNRS analytical center in Solaize (Lyon).
Z–OOC
O–R
Z
OMe
DPPA,
Et3N d
COOEt
COOEt
N
N
Me
4-Benzyl 2-Ethyl 1-Methyl-3-hydroxy-1H-pyrrole-2,4-dicar-
boxylate (10)
Me
2
Z = Et, R = H
BnONaa
13
Z = N=C=O
Z = NHCbz
Z = NHAlloc
Z = NHBoc
R–OH e
Compound 2 (20.0 g, 83.0 mmol) was added to an ice-cold solution
of sodium metal (2.7 g, 116.0 mmol) in benzyl alcohol (172.0 mL).
The resulting mixture was stirred at r.t. for 30 min, then it was heat-
ed at 100°C under reduced pressure (10 Torr) for 4 h, in order to
completely remove the liberated EtOH. Most of the benzyl alcohol
was then distilled by lowering of the pressure to 1 Torr with contin-
ued heating at 100°C. The residue thus obtained was partitioned be-
tween Et2O (100 mL) and H2O (20 mL) and the mixture was taken
to pH 5 with 4 N HCl. The layers were separated and the aqueous
phase was extracted with Et2O (2 × 20 mL). The combined extracts
were washed with sat. aq NaHCO3 (20 mL) and brine (20 mL), dried
(Na2SO4), and evaporated. Recrystallization of the solid residue
(cyclohexane) afforded 20.0 g (79%) of pure 10; mp 88°C.
10 Z = Bn, R = H
11 Z = Bn, R = Me
12 Z = H, R = Me
14
6
b
Me2SO4
10%Pd/Cc
7
Boc–HN
OMe
BnONaa
COO-R
N
7
Me
15
16
1
R = Bn
R = H
R = At
10% Pd/Cc
HOAtf
1H NMR: d = 1.35 (t, J = 7.35 Hz, 3 H), 3.75 (s, 3 H), 4.33 (q,
J = 7.35 Hz, 2 H), 5.26 (s, 2 H), 7.07 (s, 1 H), 7.20-7.40 (m, 5 H),
8.73 (s, 1 H).
13C NMR: d = 14.41, 38.08, 60.26, 65.58, 101.95, 107.55, 128.00,
128.07, 128.49, 130.12, 136.18, 154.34, 161.92, 163.86.
Reagents and conditions: a) BnOH, 100°C, 10 Torr, 4 h, 79% for 10,
87% for 15; b) K2CO3/acetone, reflux, 24 h, 88%; c) H2, 50 bar,
~100%; d) MeCN, 85°C, 2 h; e) allyl alcohol (80%) or t-BuOH (70%)
or BnOH (78%), 100 °C, 17 h; f) DCC/DMAP/CH2Cl2, r.t., 20 h, 90%
Scheme 2
IR (KBr): n = 3127, 1719, 1645 cm-1.
MS: m/z = 304, 303 (M+), 195, 150, 123, 91.
Exposure of 2 to sodium benzyloxide induced chemose-
lective transesterification at the C-4 carboxy unit. The
emerging 10 was O-methylated prior to hydrogenolysis of
HRMS: m/z calcd for C16H17NO5 303.1107, found 303.1106.
Anal. calcd for C16H17NO5: C 63.36, H 5.65, N 4.62; found: C
the benzyl group and intermediate acid 12 was subjected 63.58, H 5.54, N 4.77.
to Curtius rearrangement. The presumed isocyanate
intermediate8 was readily intercepted with allyl alcohol,
t-BuOH or BnOH to furnish the corresponding carbam-
ates 6, 7 and 14 in 80, 70 and 78% yields, respectively. A
second transesterification of 7 exchanged the C-2 ethyl es-
ter with a benzyl ester, which was hydrogenolyzed at
room temperature to give the sensitive acid 16 in quanti-
tative yield.
4-Benzyl 2-Ethyl 1-Methyl-3-methoxy-1H-pyrrole-2,4-dicar-
boxylate (11)
Dimethyl sulfate (6.7 mL, 71.2 mmol) was added dropwise to a so-
lution of 10 (18.0 g, 59.3 mmol) in anhyd acetone (180.0 mL) con-
taining suspended K2CO3 (325 mesh, 16.4 g, 118.7 mmol). The
resulting mixture was refluxed for 24 h under argon. Concentration
left a residue that was partitioned between Et2O (100 mL) and H2O
(50 mL). The aqueous layer was extracted with Et2O (2 × 20 mL)
and the combined extracts were dried (Na2SO4) and evaporated.
Synthesis 2000, No. 5, 673–676 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Practical Synthesis of Active Esters of 4-Alkoxycarbonylamino-3-methoxypyrrole-2-carboxylic Acid
675
Purification of the residue by flash chromatography (100 g of silica
gel, 20% EtOAc/hexane) afforded 16.6 g (88%) of pure 11 as an oil.
J = 1.5, 10.3 Hz, 1 H), 5.34 (dd, J = 1.5, 17.7 Hz, 1 H), 5.86-6.10
(m, 1 H), 6.48 (br s, 1 H), 7.02 (s, 1 H).
1H NMR: d = 1.36 (t, J = 7.35 Hz, 3 H), 3.83 (s, 3 H), 3.86 (s, 3 H),
4.32 (q, J = 7.35 Hz, 2 H), 5.27 (s, 2 H), 7.21 (s, 1 H), 7.25-7.45
(m, 5 H).
13C NMR: d = 14.35, 38.47, 60.15, 62.91, 65.63, 107.41, 114.76,
128.06, 128.07, 128.54, 130.79, 136.47, 153.27, 160.76, 162.50.
IR (neat): n = 2981, 1696, 1551 cm-1.
MS: m/z = 318, 317 (M+), 255, 210, 180, 150, 91.
13C NMR: d = 14.36, 37.64, 59.79, 62.72, 65.97, 110.87, 114.38,
117.66, 118.14, 132.53, 142.58, 153.38, 160.49.
IR (neat): n = 3321, 2983, 1695, 1599 cm-1.
MS: m/z = 283, 282 (M+), 197, 179, 151.
HRMS: m/z calcd for C13H18N2O5 282.1215, found 282.1208.
Ethyl 4-[(Benzyloxycarbonyl)amino]-3-methoxy-1-methyl-1H-
pyrrole-2-carboxylate (14)
HRMS: m/z calcd for C17H19NO5 317.1263, found 317.1266.
The reaction was carried out as described above by starting with
acid 12 (2 mmol) and by using benzyl alcohol (1.0 mL) to intercept
the isocyanate. Chromatographic purification (25 g of silica gel,
15% EtOAc in hexane) of crude material yielded 518 mg (78%) of
14 as an oil.
1H NMR: d = 1.35 (t, J = 7.35 Hz, 3 H), 3.77 (s, 3 H), 3.79 (s, 3 H),
4.30 (q, J = 7.35 Hz, 2 H), 5.16 (s, 2 H), 6.63 (br s, 1 H), 7.04 (s, 1
H), 7.30-7.41 (m, 5 H).
13C NMR: d = 14.35, 37.63, 59.79, 62.71, 67.15, 110.86, 114.37,
117.64, 128.23, 128.28, 128.42, 128.56, 136.12, 142.57, 153.49,
160.48.
IR (neat): n = 3325, 2980, 1694, 1598 cm-1.
Ethyl 4-Carboxy-3-methoxy-1-methyl-1H-pyrrole-2-carbox-
ylate (12)
A solution of 11 (15.0 g, 47.3 mmol) in dioxane (150.0 mL) contain-
ing 10% Pd/C (750.0 mg) was stirred under hydrogen pressure (50
bar) overnight. The catalyst was filtered off (cotton plug) and
washed with more dioxane. Concentration of the combined filtrates
afforded solid acid 12 (10.7 g, ~100%); mp 153°C (EtOH).
1H NMR: d = 1.36 (t, J = 7.35 Hz, 3 H), 3.84 (s, 3 H), 3.91 (s, 3 H),
4.32 (q, J = 7.35 Hz, 2 H), 7.27 (s, 1 H).
13C NMR: d = 14.33, 38.69, 60.31, 63.14, 106.72, 114.80, 131.43,
153.34, 160.57, 167.36.
IR (KBr): n = 2984, 1684, 1556, 1524 cm-1.
MS: m/z = 227 (M+), 180, 155, 152, 42.
MS: m/z 333, 332 (M+), 224, 197, 151, 91.
HRMS: m/z calcd for C17H20N2O5 332.1372, found 332.1368.
Anal. calcd. for C17H20N2O5: C 61.44, H 6.07, N 8.43; found C
61.47, H 6.27; N 8.27.
HRMS: m/z calcd for C10H13NO5 227.0794, found 227.0792.
Anal. calcd for C10H13NO5: C 52.86; H 5.77; N 6.17; found: C
52.97; H 5.84; N 6.20.
Benzyl 4-[(tert-Butyloxycarbonyl)amino]-3-methoxy-1-methyl-
1H-pyrrole-2-carboxylate (15)
Compound 7 (7.5 g, 25.0 mmol) was added to an ice-cold solution
of sodium (288.0 mg, 12.5 mmol) in benzyl alcohol (38.0 mL) and
the resulting mixture was processed under vacuum as detailed ear-
lier for 10, except that heating at 100°C (10 Torr) was continued for
only 1 h. The residue obtained upon removal of benzyl alcohol was
partitioned between Et2O (100 mL) and aq sat. NH4Cl (20 mL). The
layers were separated and the aqueous phase was washed with Et2O
(2 × 20 mL). The combined extracts were washed with brine (20
mL), dried (Na2SO4) and evaporated. Chromatographic purification
(100 g of silica gel, 15% EtOAc in hexane) of the residue afforded
7.9 g (87%) of 15 as an oil.
1H NMR: d = 1.49 (s, 9 H), 3.73 (s, 3 H), 3.78 (s, 3 H), 5.31 (s, 2 H),
6.25 (br s, 1 H), 7.05 (s, 1 H), 7.30-7.50 (m, 5 H).
13C NMR: d = 28.27, 37.58, 62.75, 65.49, 80.21, 110.41, 114.89,
117.94, 127.98, 128.04, 128.44, 136.27, 142.75, 152.94, 160.19.
Ethyl 4-[(tert-Butyloxycarbonyl)amino]-3-methoxy-1-methyl-
1H-pyrrole-2-carboxylate (7)
Diphenylphosphoryl azide (10.0 mL, 46.5 mmol) was added drop-
wise to an ice-cold slurry of 12 (10.0 g, 44.0 mmol) in anhyd MeCN
(44.0 mL) and Et3N (6.5 mL, 46.5 mmol). The resulting mixture
was heated at 85°C for 2 h under argon, then it was cooled to r.t.,
treated with t-BuOH (88.0 mL), and again heated at 100°C for an-
other 17 h, with good stirring. The cooled mixture was concentrated
and the residue was partitioned between Et2O (100 mL) and aq 10%
Na2CO3 solution (50 mL). The layers were separated and the aque-
ous layer was extracted with Et2O (2 × 20 mL). The combined ex-
tracts were dried (Na2SO4) and concentrated. Chromatographic
purification (150 g of silica gel, 15% EtOAc in hexane) of the resi-
due furnished 9.2 g (70%) of pure 7 as an oil.
1H NMR: d = 1.34 (t, J = 7.35 Hz, 3 H), 1.47 (s, 9 H), 3.75 (s, 3 H),
3.79 (s, 3 H), 4.29 (q, J = 7.35 Hz, 2 H), 6.29 (br s, 1 H), 7.00 (br s,
1 H).
13C NMR: d = 14.39, 28.35, 37.59, 59.77, 62.72, 80.31, 110.74,
114.87, 117.46, 129.85, 142.40, 153.00, 160.57.
IR (neat): n = 3335, 2977, 1695, 1597 cm-1.
MS: m/z = 360 (M+), 304, 260, 91, 57.
HRMS: m/z calcd for C19H24N2O5 360.1685, found 360.1680.
IR (neat): n = 3338, 2979, 1696, 1598 cm-1.
MS: m/z = 298 (M+), 283, 242, 198, 180.
HOAt Ester of 4-[(tert-Butyloxycarbonyl)amino]-3-methoxy-1-
methyl-1H-pyrrole-2-carboxylic Acid (1)
HRMS: m/z calcd for C14H22N2O5 298.1529, found 298.1530.
A solution of 15 (7.2 g, 20.0 mmol) in dioxane (72.0 mL) containing
10% Pd/C (360.0 mg) was stirred under hydrogen pressure (40 bar)
for 4 h. The catalyst was filtered off (cotton plug) and washed with
dioxane (20 mL). Concentration of the combined filtrates under re-
duced pressure at below 40°C provided acid 16 in quantitative
yield. This sensitive material was immediately taken up in anhyd
CH2Cl2 (40 mL). The chilled (0°C) solution was treated with 4-di-
methylaminopyridine (244.0 mg, 2.0 mmol), 1-hydroxypyridotriaz-
ole (HOAt, 4.1 g, 30.0 mmol) and DCC (6.2 g, 30 mmol), added in
that order, with good stirring at 0°C under argon. The mixture was
allowed to warm up to r.t. over 20 h, then it was filtered through a
sintered glass funnel to remove the precipitate, which was washed
Ethyl 4-[(Allyloxycarbonyl)amino]-3-methoxy-1-methyl-1H-
pyrrole-2-carboxylate (6)
The reaction was carried out as described above by starting with
acid 12 (2.0 mmol) and by using allylic alcohol (2.0 mL) to intercept
the isocyanate. Chromatographic purification (25 g of silica gel,
15% EtOAc in hexane) of crude material yielded 452 mg (80%) of
6 as an oil.
1H NMR: d = 1.36 (t, J = 7.35 Hz, 3 H), 3.78 (s, 3 H), 3.80 (s, 3 H),
4.31 (q, J = 7.35 Hz, 2 H), 4.62 (d, J = 5.9 Hz, 2 H), 5.24 (dd,
Synthesis 2000, No. 5, 673–676 ISSN 0039-7881 © Thieme Stuttgart · New York

676
K. Narkunan, M. A. Ciufolini
PAPER
with additional CH2Cl2 (50 mL). The combined filtrates were
washed with 0.05 N HCl (3 × 35 mL) and H2O (3 × 30 mL), dried
(Na2SO4) and evaporated. The residue was dissolved in a minimum
amount of CH2Cl2 (5 mL). Addition of hexane (50 mL) induced pre-
cipitation of practically pure 1 (7.0 g, 90%); mp 158°C.
1H NMR: d = 1.44 (s, 9 H), 3.76 (s, 3 H), 3.98 (s, 3 H), 6.65 (br s, 1
H), 7.30-7.45 (m, 2 H), 8.39-8.41 (m, 1 H), 8.68-8.72 (m, 1 H).
13C NMR: d = 28.25, 37.66, 63.25, 80.69, 105.29, 115.94, 120.71,
122.92, 129.39, 134.99, 141.05, 145.21, 151.63, 152.93, 156.12.
IR (KBr): n = 3235, 3090, 2975, 1761, 1714, 1602, 1554 cm-1.
MS: m/z = 388 (M+), 332, 253, 197, 125, 84.
Int. Ed. Engl. 1998, 37, 1421.
(d) Turner, J. M.; Swalley, S. E.; Baird, E. E.; Dervan, P. B. J.
Am. Chem. Soc. 1998, 120, 6219.
(2) The synthesis of distamycin and related compounds has been
summarized in an excellent review: Bailly, C.; Chaires, J. B.
Bioconjugate Chem. 1998, 9, 513.
(3) (a) Van Dyke, M. W.; Hertzberg, R. P.; Dervan, P. B. Proc.
Natl. Acad. Sci. U. S. A. 1983, 79, 5470.
(b) Kopka, M. L.; Yoon, C.; Goodsell, D.; Pjura, P.;
Dickerson, R. E. Proc. Natl. Acad.Sci. U. S. A. 1985, 82, 1376.
(c) Klevit, R. E.; Wemmer, D. E.; Reid, B. R. Biochemistry
1986, 25, 3296.
(4) Baird, E. E.; Dervan, P. B. J. Am. Chem. Soc. 1996, 118, 6141.
(5) Dervan, P. B. World Patent WO 97/30975. Chem. Abstr.
1997, 127, 263060.
(6) Momose, T.; Tanaka, T.; Yokota, T.; Nagamoto, N.; Yamada,
K. Chem. Pharm. Bull. 1978, 26, 2224.
HRMS: m/z calcd for C17H20N6O5 388.1495, found 388.1484.
Anal. calcd for C17H20N6O5 C 52.57; H 5.19; N 21.64; found C
52.96; H 5.23; N 21.23.
(7) Ninomiya, K.; Shioiri, T.; Yamada, S. Tetrahedron 1974, 30,
2151.
(8) This sensitive material was not isolated.
Acknowledgement
We thank the CNRS (postdoctoral fellowship to K. N.), the
MENRT, and the Région Rhône-Alpes for support of our research
program. We are grateful to Dr. Daniela Fattori, of IRBM, S.p.A.,
Pomezia, Italy, and to her colleagues, for valuable discussion.
(9) Gendler, P. L.; Rapoport, H. J. Med. Chem. 1981, 24, 33.
(10) Note added in proof. Subsequent to the acceptance of this
manuscript, Dervan and collaborators reported full details of
an alternative procedure for the large-scale synthesis of
compounds related to the ones discussed in this paper:
Urbach, A. R.; Szewczyk, J. W.; White, S.; Turner, J. M.;
Baird, E. E.; Dervan, P. B. J. Am. Chem. Soc. 1999, 121,
11621.
References
(1) (a) Herman, D. M.; Baird, E. E.; Dervan, P. B. Chem. Eur. J.
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(b) Clairac, R. P. L.; Seel, C. J.; Geierstanger, B. H.; Mrksich,
M.; Baird, E. E.; Dervan, P. B.; Wemmer, D. E. J. Am. Chem.
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Article Identifier:
1437-210X,E;2000,0,05,0673,0676,ftx,en;P05899SS.pdf
(c) Trauger, J. W.; Baird, E. E.; Dervan, P. B. Angew. Chem.
Synthesis 2000, No. 5, 673–676 ISSN 0039-7881 © Thieme Stuttgart · New York