Synthesis of the natural enantiomer of neplanocin B

Article abstract of DOI:10.1016/j.bioorg.2010.07.003

(-)-Neplanocin B, the natural isomer of a component of the neplanocin family was diasteroselectively synthesized from 2,3-O-isopropylidene-D-1,4- ribonolactone. However, when evaluated against several DNA and RNA viruses in cell culture experiments, it did not show any antiviral activity.

Full text of DOI:10.1016/j.bioorg.2010.07.003

Bioorganic Chemistry 38 (2010) 275–278
Contents lists available at ScienceDirect
Bioorganic Chemistry
journal homepage: www.elsevier.com/locate/bioorg
Synthesis of the natural enantiomer of neplanocin B
⇑
Nadège Hamon, Jean-Pierre Uttaro, Christophe Mathé , Christian Périgaud
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-UM 1-UM 2, Université Montpellier 2, cc1705, Place E. Bataillon, 34095 Montpellier cedex 5, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 June 2010
Available online 16 August 2010
(ꢀ)-Neplanocin B, the natural isomer of a component of the neplanocin family was diasteroselectively
synthesized from 2,3-O-isopropylidene-D-1,4-ribonolactone. However, when evaluated against several
DNA and RNA viruses in cell culture experiments, it did not show any antiviral activity.
Ó 2010 Elsevier Inc. All rights reserved.
Keywords:
Neplanocin derivatives
Natural product
Carbocyclic nucleosides
1. Introduction
2. Experimental
The neplanocin derivatives are an important class of naturally
occurring carbocyclic nucleosides isolated from the culture filtrate
of soil fungus Ampullariella regularis [1,2]. Five distinct components
were identified: (ꢀ)-neplanocin A (1), (ꢀ)-neplanocin B (2), (ꢀ)-
neplanocin C (3), (ꢀ)-neplanocin D (4) and (ꢀ)-neplanocin F (5)
(Fig. 1). Among these compounds, (ꢀ)-neplanocin A received great
attention due to its interesting biological properties [3,4] and
numerous syntheses of neplanocin A as well as of their analogs
were reported [5]. Indeed, (ꢀ)-neplanocin A, the lead compound
of the neplanocin family has been recognized as a potent inhibitor
2.1. General methods
Evaporation of solvents was carried out on a rotary evaporator
under reduced pressure. Melting points were determined in open
capillary tubes on a Gallenkamp MFB-595-010 M apparatus and
are uncorrected. UV spectra were recorded on an Uvikon 931
(Kontron) spectrophotometer. 1H NMR spectra were recorded at
300 MHz, 13C NMR spectra at 100 MHz and 19F NMR at 235 MHz
in (CD3)2SO at ambient temperature with a Brüker DRX 400.
Chemical shifts (d) are quoted in parts per million (ppm) refer-
enced to the residual solvent peak, (CD3)CD2H)SO being set at
d-H 2.49 and d-C 39.5 relative to tetramethylsilane (TMS). Deute-
rium exchange and COSY experiments were performed in order
to confirm proton assignments. Coupling constants, J, are reported
in Hertz. 2D 1H–13C heteronuclear COSY were recorded for the
attribution of 13C signals. Specific rotations were measured on a
Perkin–Elmer Model 241 spectropolarimeter (path length 1 cm),
and are given in units of 10ꢀ1 deg cm2 gꢀ1. Elemental analyses
were carried out by the Service de Microanalyses du CNRS, Divi-
sion de Vernaison (France). Thin layer chromatography was per-
formed on precoated aluminum sheets of Silica Gel 60 F254
(Merck, Art. 5554), visualization of products being accomplished
by UV absorbency followed by charring with 5% ethanolic sulfuric
acid and heating. Column chromatography was carried out on Sil-
ica Gel 60 (Merck, Art. 9385). All moisture-sensitive reactions
were carried out under rigorous anhydrous conditions under an
argon atmosphere using oven-dried glassware. Solvents were
dried and distilled prior to use and solids were dried over P2O5
under reduced pressure.
of S-adenosyl-L-homocysteine (AdoHcy) hydrolase. Inhibition of
AdoHcy hydrolase leads to the accumulation of AdoHcy which is
a feedback inhibitor of S-adenosyl methionine-dependent methyl-
transferases. Such methylation reactions are required for the 50-
capping of viral mRNAs leading to the inhibition of the maturation
of mRNAs which provides an antiviral effect [3].
In a less extent, only few syntheses of the other natural compo-
nents of the neplanocin family have been reported in the literature.
The total synthesis of (+/ꢀ)-neplanocin F as a racemate [6] as well
as the enantioselective synthesis of its unnatural (+) [7] and natu-
ral (ꢀ)-enantiomer [8] were described. The synthesis of (+) and
(ꢀ)-neplanocin D [9] as well as (ꢀ)-neplanocin C [10] were also re-
ported. In contrast, only the synthesis of the unnatural (+)-enantio-
mer of neplanocin B was published [11].
In this context, and in order to evaluate its antiviral properties,
we report herein the first synthesis of the natural enantiomer.
⇑
Corresponding author. Fax: +33 (0)4 67 04 20 29.
E-mail address: christophe.mathe@univ-montp2.fr (C. Mathé).
0045-2068/$ - see front matter Ó 2010 Elsevier Inc. All rights reserved.
doi:10.1016/j.bioorg.2010.07.003

276
N. Hamon et al. / Bioorganic Chemistry 38 (2010) 275–278
7.33–7.39 (m, 5H), 7.21–7.25 (m, 3H), 7.17–7.20 (m, 2H), 6.11 (d,
J = 1.2 Hz, 1H), 5.19 (m, 1H), 5.07 (m, 1H), 4.71 (d, J = 12.0 Hz,
1H), 4.65 (d, J = 6.3 Hz, 1H), 4.62 (s, 2H), 4.49 (d, J = 12.0 Hz, 1H),
4.30 (s, 2H), 4.17 (d, J = 4.2 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d
151.3, 151.2, 150.9, 145.4, 143.6, 137.6, 137.6, 131.9, 128.5,
128.3, 128.0, 127.9, 127.8, 126.4, 80.6, 75.9, 73.1, 72.6, 71.7, 66.5;
FAB-MS (>0) m/z 463 [M + H]+. HRMS TOF MS E+ for C25H24ClN4O3:
calculated: 463.1537 found: 463.1547. Anal. Calcd for
C25H23ClN4O3. 0.35 Et2O: C, 64.86; H, 5.46; N, 11.46. Found: C,
64.64; H, 5.86; N, 11.35.
2.4. (ꢀ)-(1S,2R,3R,4S,5R)-4-(benzyloxy)-1-[(benzyloxy)methyl]-3-(6-
chloro-9H-purin-9-yl)-6-oxabicyclo[3.1.0]hexan-2-ol (9)
To as solution of 8 (158 mg, 0.34 mmol) in CH2Cl2 (7.2 mL) at
0 °C was added a solution of m-CPBA (124 mg, 0.72 mmol) in
CH2Cl2 (3.6 mL). The reaction mixture was stirred at room temper-
ature for 21 h and solvent was evaporated under reduced pressure.
The residue was purified by column chromatography using diethyl
ether to afford 9 as a white foam (503 mg, 93% yield): Rf (diethyl
ether) 0.36; UV (EtOH, 96%) kmax = 266.0 nm (
ꢀ
= 9500); ½a 2D0
ꢀ41
ꢂ
(c 1.0, CHCl3); 1H NMR (CDCl3, 300 MHz) d 8.44 (s, 1H), 8.07 (s,
1H), 7.27–7.38 (m, 5H), 6.89–6.98 (m, 5H), 5.05 (m, 1H), 5.02 (m,
1H), 4.71 (dd, J = 1.2, 8.1 Hz, 1H), 4.65 (s, 2H), 4.64 (d, J = 12.3 Hz,
1H), 4.37 (t, J = 7.6 Hz, 1H), 4.32 (d, J = 12.2 Hz, 1H), 4.08 (d,
J = 11.4 Hz, 1H), 3.85 (d, J = 11.4 Hz, 1H), 3.78 (d, J = 0.9 Hz, 1H);
13C NMR (CDCl3, 75 MHz) d 151.2, 150.7, 150.1, 146.9, 137.4,
136.7, 131.4, 128.5, 127.9, 127.9, 127.8, 127.6, 75.1, 73.8, 71.8,
70.5, 66.9, 56.4, 63.5, 57.6; FAB-MS (>0) m/z 479 [M+H]+. Anal.
Calcd for C25H23ClN4O4. 0.35 Et2O: C, 62.80; N, 11.10; Found: C,
62.97; N, 10.72.
Fig. 1. Naturally occurring carbocyclic nucleosides from the neplanocin family.
2.2. (ꢀ)-9-[(1S,2S,5R)-5-(benzyloxy)-3-[(benzyloxy)methyl]-2-
(methoxymethoxy)-3-cyclopenten-1-yl]-6-chloro-9H-purine (7)
To a solution of 6 (1.12 g, 2.23 mmol) in dry DMF (22.5 mL) was
added successively K2CO3 (971 mg, 7.03 mmol), 6-chloropurine
(776 mg, 5.02 mmol) and 18-crown-6 ether (206 mg, 0.78 mmol).
The mixture was heated at 60 °C for 3 h and poured into brine
(125 mL) and ethyl acetate (125 mL). The aqueous phase was ex-
tracted with ethyl acetate (3 ꢁ 125 mL) and the combined organic
phases were washed with brine (2 ꢁ 125 mL), dried (MgSO4), and
evaporated under reduced pressure. Purification by column chro-
matography using diethyl ether/methylene chloride (5/95 to 10/
90, v/v) gave 7 as a yellow solid (686 mg, 60% yield): mp 93–94
2.5. (ꢀ)-(1S,2S,3R,4R,5R)-3-(6-amino-9H-purin-9-yl)-4-(benzyloxy)-
1-[(benzyloxy)methyl]-6-oxabicyclo[3.1.0]hexan-2-ol (10)
A solution of 9 (716 mg, 13.9 mmol) in saturated methanolic
ammonia (35 mL) in a steel bomb was heated at 70 °C for 14 h.
The reaction mixture was cooled and the solvent removed under
reduced pressure. The residue was purified by column chromatog-
raphy using ethyl acetate/methanol (96:4; v/v) to afford 10 as a
white foam (375 mg, 50% yield); Rf (ethyl acetate/methanol, 9:1)
°C; Rf: (diethyl ether) 0.41; UV (EtOH, 96%) kmax = 266.0 nm (
ꢀ
9000); ½a 2D0
ꢂ
ꢀ23 (c 1.0, CHCl3); 1H NMR (CDCl3, 300 MHz) d 8.62
0.37; UV (EtOH, 96%) kmax = 260.0 nm (
ꢀ
= 12,500); ½a 2D0
ꢀ37 (c
ꢂ
(s, 1H), 7.96 (s, 1H), 7.31–7.38 (m, 5H), 7.10–7.13 (m, 3H), 7.01–
7.04 (m, 2H), 6.12 (s, 1H), 5.13 (d, J = 6.0 Hz, 1H), 5.02 (d,
J = 5.7 Hz, 1H), 4.72 (t, J = 6.0 Hz, 1H), 4.63 (d, J = 12.0 Hz, 1H),
4.59 (d, J = 12.0 Hz, 1H), 4.55 (d, J = 12.0 Hz, 1H), 4.45 (s, 2H),
4.37 (d, J = 12.0 Hz, 1H), 4.19 (d, J = 5.4 Hz, 2H), 3.07 (s, 3H); 13C
NMR (CDCl3, 75 MHz) d 151.3, 151.0, 145.8, 143.0, 137.7, 137.3,
132.3, 128.4, 128.2, 127.9, 127.8, 127.8, 127.7, 127.6, 97.0, 82.5,
81.5, 72.8, 72.0, 71.1, 65.9, 55.5; FAB-MS (>0) m/z 507 [M + H]+.
HRMS TOF MS E+ for C27H28ClN4O4: calculated: 507.1799 found:
507.1800. Anal. Calcd for C27H27ClN4O4. 0.1 Et2O: C, 63.98; H,
5.49, N, 10.99. Found: C, 63.63; H, 5.28; N, 10.97.
1.0, DMSO); 1H NMR (CDCl3, 300 MHz) d 8.13 (s, 1H), 7.69 (s,
1H), 7.38–7.15 (m, 10H), 5.65 (br s, 2H), 5.43 (br s, 1H), 4.87 (d,
J = 7.2 Hz, 1H), 4.72 (d, J = 12.0 Hz, 1H), 4.58–4.67 (m, 3H), 4.54
(d, J = 12.0 Hz, 1H), 4.29 (t, J = 7.3 Hz, 1H), 4.03 (d, J = 11.4 Hz,
1H), 3.83 (d, J = 11.1 Hz, 1H), 3.73 (s, 1H); 13C NMR (CDCl3,
75 MHz) d 155.1, 151.9, 149.5, 141.4, 137.5, 136.9, 128.5, 128.3,
127.9, 127.9, 127.7, 119.9, 76.4, 73.8, 71.5, 70.7, 66.9, 64.2, 63.4,
57.6; FAB-MS (>0) m/z 460 [M + H]+. HRMS TOF MS E+ for
C25H26N5O4: calculated: 460.1985 found: 460.1986. Anal. Calcd
for C25H25N5O4. 0.75 MeOH: C, 63.96; H, 5.84; N, 14.48; Found:
C, 64.17; H, 6.24; N, 14.87.
2.3. (ꢀ)-(1S,4R,5R)-4-(benzyloxy)-2-[(benzyloxy)methyl]-5-(6-
chloro-9H-purin-9-yl)-2-cyclopenten-1-ol (8)
2.6. (ꢀ)-(1S,2S,3S,4R,5R)-3-(6-amino-9H-purin-9-yl)-1-
(hydroxymethyl)-6-oxabicyclo[3.1.0]hexane-2,4-diol (2)
To a solution of 7 (1.5 g, 2.96 mmol) in CH2Cl2 (59 mL) was
added dropwise TFA (14.8 mL). The solution was stirred at room
temperature for 28 h, then poured into an aqueous saturated NaH-
CO3 solution (400 mL) and extracted with CH2Cl2 (3 ꢁ 200 mL). The
combined organic layers were dried (MgSO4) and evaporated to
dryness. A purification by column chromatography using diethyl
ether gave 8 as a white foam (832 mg, 60% yield): Rf (diethyl ether)
To a solution of 10 (375 mg, 0.82 mmol) in methanol (9.1 mL)
was added ammonium formate (772 mg, 12.3 mmol) and 10% Pd/
C (390 mg). The mixture was stirred at reflux for 18 h and filtrated
through a pad of Celite before evaporation of solvent. The residue
was purified by column chromatography using ethyl acetate/meth-
anol (3:1, v/v) to give 2 as a white solid (44 mg, 20% yield); mp
270 °C; Rf (iPrOH, H2O, NH4OH 5:1:1) 0.61; UV (H2O)
0.36; UV (EtOH, 96%) kmax = 266.0 nm (
ꢀ
= 7200); ½a 2D0
ꢂ
ꢀ50 (c 1.0,
kmax = 260.0 nm; ½a D20
ꢂ
ꢀ3.0 (c 1.0, DMSO); 1H NMR (DMSO-d6,
CHCl3); 1H NMR (CDCl3, 300 MHz) d 8.67 (s, 1H), 8.04 (s, 1H),
300 MHz): d 8.05 (br s, 1H), 8.02 (s, 1H) 7.21 (s, 2H, NH2), 5.50

N. Hamon et al. / Bioorganic Chemistry 38 (2010) 275–278
277
Table 1
(br s, 2H), 4.93 (br s, 1H), 4.70 (m, 1H), 4.64 (m, 1H), 4.06 (t,
J = 7.8 Hz, 1H), 3.88 (dd, J = 4.2 Hz, 12.3 Hz, 1H), 3.52 (m, 2H); 13C
NMR (DMSO-d6, 75 MHz) d 156.1, 152.0, 149.8, 141.9, 119.7,
69.74, 69.7, 64.7, 64.69, 59.3, 57.6; FAB-MS (>0) m/z 280 [M+H]+.
HRMS TOF MS E+ for C11H14N5O4: calculated: 280.1046 found:
280.1041.
Catalytic hydrogenation conditions.
Entry
Conditions
Compound 2 (yield)
1
2
3
4
5
6
7
8
9
H2, 5%Pd/C, MeOH, r.t., 1 atm
H2, 10%Pd/C, MeOH, r.t., 1 atm
No deprotection
No deprotection
No deprotection
No deprotection
No deprotection
No deprotection
Trace
H2, 5%Pd/C, HCO2H, MeOH, r.t., 3 atm
H2, 5% Pd black, HCO2H, MeOH, r.t., 3 atm
H2, Pd(OH)2, EtOAc/MeOH, r.t., 1 atm
H2, Ni Raney, EtOH, r.t., 1 atm.
HCO2NH4 (28 eq.), Pd(OH)2, EtOH, reflux
HCO2NH4 (5 eq.), 10% Pd/C, MeOH, reflux
HCO2NH4 (10 eq.), 10% Pd/C, MeOH, reflux
3. Results and discussion
Trace
20%
The synthesis of (ꢀ)-neplanocin B was achieved from the prep-
aration of a suitable carbocyclic precursor (6) bearing appropriate
protective groups (Fig. 1). Such an intermediate can be obtained
hydrogenation reaction have been investigated. Whatever the con-
ditions used, no debenzylation occured. Nevertheless, compound
10 was finally deprotected (entry 9) by treatment with ammonium
formate and Pd/C in MeOH to afford the target molecule (ꢀ)-nepla-
nocin B (2). The 1H NMR and 13C NMR were identical with those
previously reported for the unnatural enantiomer. The optical rota-
tion value was in agreement with the one previously reported [2].
in several steps from commercially available
D-c-ribonolactone
[8]. Thus, treatment of 6 with K2CO3, 6-chloropurine and a catalytic
amount of 18-crown-6 ether in dry DMF at 60 °C afforded only the
N-9 alkylated compound 7. The structure of 7 was fully established
from 1H, 13C NMR and UV spectra. The selective removal of MOM
group was carried out with diluted TFA in methylene chloride.
Compound 8 was treated with m-chloroperbenzoic acid to give ste-
reoselectively the epoxy derivative 9 in 93% yield. The epoxidation
reaction was directed by the allylic alcohol and gave a single dia-
stereoisomer [12]. Treatment with methanolic ammonia afforded
the desired carbocyclic analog 10 (see Fig. 2).
4. Conclusion
In summary, the synthesis of the natural isomer (ꢀ)-neplanocin
Once the synthesis of the carbocyclic intermediate 10 was
achieved, removal of the benzyl groups was envisioned via a cata-
lytic hydrogenation [13]. Different reaction conditions were at-
tempted (Table 1).
B (2) was carried out from 2,3-O-isopropylidene-D-1,4-ribonolac-
tone. However, when the carbocyclic nucleoside 2 was evaluated
against several DNA and RNA viruses in cell culture experiments,
compound 2 did not showed any antiviral activity nor cytotoxicity
Catalytic hydrogenation of compound 10 in the presence of
Pd/C was not as effective as previously reported [11]. The influence
of pressure, temperature, solvent and the catalyst on the
at the highest concentration tested (usually 100 lM).
Acknowledgments
One of us N.H. is particularly grateful to the Ministère de l’Edu-
cation Nationale, de la Recherche et de la Technologie (France) for a
doctoral fellowship. We gratefully acknowledge Pr. J. Balzarini
(Laboratory of virology and chemotherapy, Katholieke Universiteit,
Leuven) for the biological results.
References
[1] (a) M. Hayashi, S. Yaginuma, N. Muto, M. Tsujino, Nucl. Acids. Res. Symp. Ser. 8
(1980) s65;
(b) M. Hayashi, S. Yaginuma, H. Yoshioka, K. Nakatsu, J. Antibiot. 34 (1981)
675;
(c) S. Yaginuma, N. Muto, M. Tsujino, Y. Sudate, M. Hayashi, M. Otani, J.
Antibiot. 34 (1981) 359.
[2] S. Yaginuma, M. Tsujino, N. Muto, M. Otani, M. Hayashi, F. Ishimura, T. Fujii,
S. Watanabe, T. Matsuda, T. Watanabe, J. Abe, in: J.D. Nelson, C. Grassi (Eds.),
Current Chemotherapy and Infectious Diseases, vol. 2, American Society for
Chemotherapy, Washington DC, 1979, pp. 1558–1559.
[3] E. De Clercq, Antimicrob. Agents Chemother. 28 (1985) 84.
[4] (a) E. De Clercq, R. Bernaerts, D.E. Bregstrom, M.J. Robins, J.A. Montgomery, A.
Holy, Antimicrob. Agents Chemother. 29 (1986) 482;
(b) E. De Clercq, Nucleosides Nucleotides 17 (1998) 625;
(c) K. Isono, J. Antibiot. 41 (1988) 1711;
(d) K. Isono, Pharmacol. Ther. 52 (1991) 269;
(e) S. Rachakonda, L. Cartee, Curr. Med. Chem. 11 (2004) 775.
[5] (a) L.S. Hegedus, L. Geisler, J. Org. Chem. 65 (2000) 4200;
(b) D.H. Shin, H.W. Lee, S.S. Park, J.H. Kim, L.S. Jeong, M.W. Chun, Arch. Pharm.
Res. 23 (2000) 302;
(c) M. Ono, K. Nishimura, H. Tsubouchi, Y. Nagaoka, K. Tomioka, J. Org. Chem.
66 (2001) 8199;
(d) S. Shuto, N. Minakawa, S. Niizuma, H.S. Kim, Y. Wataya, A. Matsuda, J. Med.
Chem. 45 (2002) 748;
(e) L.S. Jeong, S.J. Yoo, K.M. Lee, M.J. Koo, W.J. Choi, H.O. Kim, H.R. Moon, M.Y.
Lee, J.G. Park, S.K. Lee, M.W. Chun, J. Med. Chem. 46 (2003) 201;
(f) K.L. Seley, S.L. Mosley, F.X. Zeng, Org. Lett. 5 (2003) 4401;
(g) H.R. Moon, H.J. Lee, K.R. Kim, K.M. Lee, S.K. Lee, H.O. Kim, M.W. Chun, L.S.
Jeong, Bioorg. Med. Chem. Lett. 14 (2004) 5641;
(h) X.Q. Yin, S.W. Schneller, Tetrahedron Lett. 46 (2005) 1927;
(i) F.A. Khan, B. Rout, J. Org. Chem. 72 (2007) 7011;
(j) B.Y. Michel, P. Strazewski, Tetrahedron 63 (2007) 9836;
(k) A.Y. Park, K.R. Kim, H.R. Lee, J.A. Kang, W.H. Kim, P. Chun, P. Ahmad, L.S.
Jeong, H.R. Moon, B. Korean Chem. Soc. 29 (2008) 2487;
Fig. 2. Reagents and conditions: (a) K2CO3, 18-crown-6 ether, DMF, 60 °C; (b) TFA
(18%)/CH2Cl2, r.t.; (c) m-CPBA/CH2Cl2, r.t.; (d) NH3/MeOH, 70 °C; (e) see Table 1.

278
N. Hamon et al. / Bioorganic Chemistry 38 (2010) 275–278
(l) H. Kumamoto, K. Deguchi, T. Wagata, Y. Furuya, Y. Odanaka, Y. Kitade, H. [8] S. Rodriguez, D. Edmont, C. Mathe, C. Perigaud, Tetrahedron 63 (2007)
Tanaka, Tetrahedron 65 (2009) 8007;
7165.
(m) H.R. Lee, J.A. Kang, A.Y. Park, W.H. Kim, P. Chun, J. Kim, J.A. Kim, B. Lee, L.S.
Jeong, H.R. Moon, B. Korean Chem. Soc. 30 (2009) 2043;
(n) W. Ye, M.Z. He, S.W. Schneller, Tetrahedron Lett. 50 (2009) 7156.
[9] G.Y. Song, V. Paul, H. Choo, J. Morrey, R.W. Sidwell, R.F. Schinazi, C.K. Chu, J.
Med. Chem. 44 (2001) 3985.
[10] M.J. Comin, J.B. Rodriguez, Tetrahedron 56 (2000) 4639.
[11] M.J. Comin, S.C. Pellegrinet, J.B. Rodriguez, Arkivoc (2005) 205.
[12] H.B. Henbest, R.A. Wilson, J. Chem. Soc. (1957) 1958.
[13] S.A. Weissman, D. Zewge, Tetrahedron 61 (2005) 7833.
[6] M. Bodenteich, V.E. Marquez, W.H. Hallows, B.M. Goldstein, J. Org. Chem. 57
(1992) 2071.
[7] M.J. Comin, J. Leitofuter, J.B. Rodriguez, Tetrahedron 58 (2002) 3129.