Synthesis of 2′,3′-cyclohexen bicyclic uridine analogues using ring-closure metathesis

Article abstract of DOI:10.1055/s-2006-941568

The synthesis of two new 2′,3′-cyclohexen bicyclic uridine analogues is described. From 5′-protected uridine two successive tin radical-mediated allylations at 2′-C and 3′-C position followed by ring-closure olefin metathesis on the diene intermediate usi

Full text of DOI:10.1055/s-2006-941568

LETTER
1339
Synthesis of 2¢,3¢-Cyclohexen Bicyclic Uridine Analogues Using Ring-Closure
Metathesis
S
ynthesis
u
of
2
¢
,3
¢
-Cycl
l
ohexen
l
Bicycl
i
ic
U
rid
e
ine
A
nalog
n
ues Drone,a Maxim Egorov,a Wilfried Hatton,a Marie-Jo Bertrand,a Christophe Len,b Jacques Lebreton*a
c
Laboratoire de Synthèse Organique, CNRS UMR 6513, Université de Nantes,
2 Rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France
Fax +33(2)51125562; E-mail: Jacques.Lebreton@univ-nantes.fr
d
Synthèse et Réactivité des Substances Naturelles, CNRS UMR 6514, FR 2703, Université de Poitiers,
40 Avenue du Recteur Pineau, 86022 Poitiers Cedex, France
Received 27 February 2006
nucleosides and nucleotides in solution.7 Three different
classes of conformationally restricted nucleoside ana-
logues have been described: (i) bicyclic and tricyclic nu-
cleosides having a bridge between two positions of the
Abstract: The synthesis of two new 2¢,3¢-cyclohexen bicyclic uri-
dine analogues is described. From 5¢-protected uridine two succes-
sive tin radical-mediated allylations at 2¢-C and 3¢-C position
followed by ring-closure olefin metathesis on the diene intermedi-
ate using Grubbs’ catalyst led to the formation of the six-membered furanose ring;8 (ii) cyclonucleosides having a bridge be-
tween the heterocyclic base and the furanose ring (c, P);9
ring.
(iii) cyclic phosphoesters having a bridge extending from
the phosphorus atom of the nucleotide to either the hetero-
cyclic base or the furanose ring (c, g).10 In the case of
bicyclic nucleosides the ring fusion to the 2¢,3¢-positions
of the glycone moiety having either C,O-connection such
as compounds 1–511–14 or C,C-connection such as com-
pounds 6–1815–22 have been reported for evaluation of
either their antiviral activity or their ability to form duplex
between an antisense oligonucleotide and the messenger
RNA target (Figure 1).
Key words: antivirals, nucleic acid analogues, radical allylation,
ring-closure metathesis
Nucleoside analogues display a large range of biological
activities as antiviral agents1 against Human Immunodefi-
ciency Virus (HIV),2 Herpes Simplex Virus (HSV)3 and
Hepatitis B Virus (HBV)4 and as antitumor agents.5 A
large number of 2¢,3¢-dideoxynucleoside analogues (dd-
Ns) and 2¢,3¢-didehydro-2¢,3¢-dideoxynucleoside ana-
logues (d4Ns) are approved by the US Food and Drug
Administration for the treatment of AIDS. The mecha-
nism of action of ddNs and d4Ns require intracellular me-
tabolization by cellular kinases into the corresponding 5¢-
triphosphate forms, which act as competitive inhibitors
and/or chain terminators. Despite the wide number of
nucleoside analogues reported, only a few effective com-
pounds have been obtained. This inactivity may be due to
either low intracellular metabolization into the corre-
sponding nucleotide derivatives or lack of activity of such
a nucleotide on the target enzyme. In the course of the
search for new agents with a higher therapeutic index, the
conformation equilibrium of nucleosides is considered as
essential. The complete definition of the conformation of
nucleosides usually involves the determination of three
principal structural parameters:6 (i) the glycosyl torsion
angle (c; syn–anti equilibrium); (ii) the torsion angle de-
termining the orientation of the 5¢-hydroxy group relative
to C3¢ (g; +sc, ap, -sc equilibrium); (iii) the conformation
of the furanose ring, i.e. its position on the pseudorotation-
al cycle as determined by the phase angle of rotation (P).
Therefore, conformationally restricted nucleoside ana-
logues have served as useful model compounds for inves-
tigations of the conformational importance of enzyme–
O
O
O
B
B
B
HO
HO
HO
HO
R
O
O
O
n(H2C)
11 1 B = T ; R = N3 ; n = 1
12,13 2 B = T ; R = OH ; n = 2
13 3 B = T ; R = OH ; n = 3
14 5 B = C
13 4 B = T
O
B
O
B
O
B
HO
HO
H
H
HO
19 9 B = T
21 14 B = T
15 6 B = T
16,17 7 B = C
18 8 B = U
19 10 B = U
19,20 11 B = C
19,20 12 B = A
19 13 B = G
O
B
HO
O
B
HO
H
H
22 16 B = T
22 17 B = U
22 18 B = C
21 15 B = T
substrate interactions and physicochemical properties of Figure 1 Bicyclic nucleosides 1–18.
As part of our drug-discovery program for antiviral agents
having restricted conformation, we have recently reported
the synthesis of the 1,3-dihydrobenzo[c]furan nucleoside
SYNLETT 2006, No. 9, pp 1339–1342
Advanced online publication: 22.05.2006
DOI: 10.1055/s-2006-941568; Art ID: G03706ST
© Georg Thieme Verlag Stuttgart · New York
0
1.
0
6.
2
0
0
6

1340
J. Drone et al.
LETTER
analogues 16–18 which had no significant anti-HIV activ- planned to take advantage of this fact for the preparation
ity.23 One explanation for this result may be related to the of the cis- and trans-diastereoisomers 19 and 20 which
steric effect of the benzene ring which does not allow the could be isolated pure after separation affording then
access of the triphosphate derivative to the enzyme nucle- enough material for preliminary biological evaluation.
otide binding site. In view of this lack of activity we de-
scribed herein the enantiomerically pure nucleoside
Starting from uridine (21), the 2¢-C-allyl-substituted nu-
cleoside 22 was constructed on the basis of known
analogues 19 and 20 having a cyclohexene ring in the
methodology for preparing 2¢-allyl-2¢-deoxynucleo-
2¢,3¢-positions of the sugar residue. These novel com-
sides.29b Selective protection of the primary hydroxyl
group of 22 as a tert-butyldiphenylsilyl (TBDPS) ether
afforded intermediate 23 in excellent yield, the stage was
set to introduce the required allyl group at C-3¢ position.
pounds were expected to (i) retain the phosphorylation
site; (ii) possess enhanced lipophilicity over ddN and d4N
derivatives; (iii) have less steric effect than the ben-
zo[c]furan analogues 16–18. Furthermore, the diastereo-
Accordingly, exposure of 23 to phenyl chlorothiocarbon-
isomeric nucleosides 19 and 20, having S and R absolute
ate (PTCCl) in the presence of N-hydroxysuccinimide
configurations for the carbon atom C-3¢, respectively, had
(NOS), as described by Barton31 in the case of hindered al-
cohol, proceeded smoothly to provide the corresponding
thiocarbonate 24 in 91% yield. Using previous allylation
procedure, no reaction took place and only starting
different conformations (especially for P parameter)
which will permit to contribute to the structure–activity
relationship studies of our group and the others regarding
antiviral nucleosides.
material was recovered. The preparation of the 3¢-C-allyl-
In this preliminary study the choice of uridine as starting uridine derivatives 25 and 26, synthesized from thio-
material was dictated by the possibility at final stage to carbonate 24 by trapping the radical in the Barton
convert an advanced intermediate into its 5-methyl conge- deoxygenation with allyltributyltin was found to be much
ner via 5-bromination and subsequent Pd-catalyzed cross- more delicate compare to the first one at C-2¢ position.
coupling reaction via trimethylaluminum24 or into cyti- After considerable experimentations, it was found that the
dine analogues via 4-triazolo intermediate25 followed by C-allylation reaction was best conducted at refluxing ben-
treatment with concentrated ammonia. Access to the tar- zene with the use of 10 equivalents of allyltributyltin, 1
get molecules 19 and 20 from uridine would be straight- equivalent of 2,2¢-azobis(isobutyronitrile) (AIBN) as ini-
forward via two successive free-radical allylations26 with tiator and 0.1 equivalents of tributyltin hydride32 to give
an appropriate C-2¢- and C-3¢-phenoxythiocarbonyl-sub- the desired key intermediates 25 and 26 in 51%33 as a
stituted uridine leading to new C–C bond formation, 75:25 mixture of cis- and trans-isomers 25 and 26 (vide
followed by a well-established ring-closing metathesis infra), as well as 6% of reduced product (Scheme 1). In
(RCM)27,28 reaction.
absence of tin hydride only starting material was recov-
ered, prolonged reaction times (up to 14 h) led to degrada-
tion. On the basis of this result, it is reasonable to suggest
that the formation of tributyltin radical in decent con-
centration due to the presence of more reactive tributyltin
hydride with AIBN permitted to initiate the reaction with
the thiocarbonyloxy group of 24. Then, the tributyltin rad-
ical led to the classical fragmentation and afforded the
alkyl radical on C-3¢, which can react with the excess of
allyltributyltin to yield the two diastereomeric diallyl de-
rivatives 25 and 26.
Radical allylation has proven to be an excellent tool to
synthesize 2¢- or 3¢-C-substituted nucleoside derivatives
giving high yields in a very practical synthetic route.29
However, previous efforts had shown that stereoselective
radical allylation at C-3¢ in ribo series was more problem-
atic compare to deoxyribo series (see ref. 6h). It should be
pointed out that same difficulties were noted in the addi-
tion of styryltributyltin to 3¢-C-centered radicals in ribo
series: low yields and/or low diastereoselectivity.30 We
U
U
U
TBDPSO
TBDPSO
TBDPSO
U
U
O
O
O
O
O
d
b
a
HO
HO
+
HO
RO
HO
OH
21
22
25
26
23 R = H
24 R = (CS)OPh
c
e
U
U
O
O
RO
RO
+
28 R = TBDPS
20 R = H
27 R = TBDPS
19 R = H
f
f
Scheme 1 Reagents and conditions: (a) ref. 29b; (b) TBDPSCl, imidazole, DMF, r.t., 12 h, 99%; (c) PTCCl, NOS, pyridine, toluene, 80 °C,
4 h, 91%; (d) Bu3Sn-allyl, AIBN, Bu3SnH, PhH, reflux, 14 h, 51%; (e) second-generation Grubbs’catalyst, CH2Cl2, r.t., 12 h, 65%; (f) NH4F,
MeOH, 60 °C, 12 h, 89%.
Synlett 2006, No. 9, 1339–1342 © Thieme Stuttgart · New York

LETTER
Synthesis of 2′,3′-Cyclohexen Bicyclic Uridine Analogues
1341
The modest stereoselectivity of the C-allylation could not
be improved. In parallel, we briefly considered the possi-
bility to use a double radical C-allylation on the 2¢,3¢-O-
thionocarbonate-uridine as a shortest alternative to reach
the diallyl intermediates 25 and 26. Unfortunately all at-
tempts failed, only 2¢,3¢-dideoxy-2¢,3¢-didehydrouridine
(d4U) was isolated in low yield (22%) even when allyl-
tributyltin was used as a solvent.34 The mixture of the di-
allylated nucleosides 25 and 26 could not be efficiently
separated by chromatography on silica gel column at this
stage of the synthesis as well as the unprotected de-
rivatives. The RCM reaction was carried on the later mix-
ture with the Grubb’s second-generation catalyst [1,3-
bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichlo-
ro(phenylmethylene)(tricyclohexylphosphine)ruthenium]
in CH2Cl2 at room temperature overnight at atmospheric
pressure under nitrogen flux to afford the mixture of de-
sired cyclohexene derivatives 27 and 28 in 65% yield after
purification. Finally, cleavage of the silyl ether protecting
group using conditions reported for nucleoside 3 led to the
target molecules 1935 and 20,36 which were separated by
preparative HPLC.37
References and Notes
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The configuration of the diastereomeric products cis-19
and trans-20 was unambiguously assigned by a set of 1D
and 2D NMR experiments, in particularly NOESY,
COSY and HSQC between the proximal hydrogen atoms,
on separated target molecules (see Figure 2).
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O
O
4
5
3 NH
NH
O
6
1
N
HO
HO
2
N
O
O
O
4'
H
1'
H
H
H
H
H
H
2'
3'
9'
H
H
H
6'
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Carbohydr. Res. 1990, 205, 87.
H
H
H
Figure 2 Selected NOE correlations for products cis-19 and
trans-20.
(18) Wu, J. C.; Chattopadhyaya, J. Tetrahedron 1990, 46, 2587.
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39, 225.
In conclusion, allyltributyltin(IV)-mediated radical C-al-
lylation and RCM have been used successfully to provide
an easy entry to a new family of bicyclic nucleosides. Ex-
tension of this work to the synthesis of other novel nucle-
osides, in particularly the corresponding thymine and
cytosine series, and the results of modeling studies and
biological tests will be reported in due course.
(21) Hossain, N.; Plavec, J.; Thibaudeau, C.; Chattopadhyaya, J.
Tetrahedron 1993, 49, 9079.
(22) Ewing, D. F.; Fahmi, N. E.; Len, C.; Mackenzie, G.; Pranzo,
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Y. Synthesis 1993, 213.
Acknowledgment
This work was supported by the Centre National de la Recherche
Scientifique (CNRS) and the University of Nantes. The authors
wish to warmly thank Dr. Alain De Mesmaeker (Syngenta, Basel,
Switzerland) for fruitful discussions concerning the tin radical-
mediated allylation.
(25) Xu, Y.-Z.; Zheng, Q.; Swann, P. F. J. Org. Chem. 1992, 57,
3839.
Synlett 2006, No. 9, 1339–1342 © Thieme Stuttgart · New York

1342
J. Drone et al.
LETTER
(26) For recent reviews on radical-based reactions, see: (a) Bar,
G.; Parsons, A. F. Chem. Soc. Rev. 2003, 32, 251.
tR = 10.5 min for minor diastereomer 26 and tR = 11.1 min
for major diastereomer 25; Rf = 0.66 (30% Et2O–PE, single
spot with these conditions)]. MS (CI/NH3): m/z 531(100) [M
+ NH3]+, 548.
(b) Renaud, P.; Sibi, M. P. Radicals in Organic Synthesis;
VCH: New York, 2001. (c) Sibi, M. P.; Porter, N. A. Acc.
Chem. Res. 1999, 32, 163.
Data for major diastereomer 25: 1H NMR (400 MHz,
CDCl3): d = 1.03 (s, 9 H, t-Bu), 1.80–2.50 (m, 6 H, H-2¢, H-
3¢, H-6¢, H-6¢¢, H-10¢ and H-10¢¢), 3.60 and 4.00 (part AB of
ABX system, 2 H, J = 2.3 Hz, J = 2.4 Hz, J = 11.8 Hz, H-5¢),
3.80 (m, 1 H, H-4¢), 4.90–5.09 (m, 4 H, H-8¢, H-9¢, H-12¢ and
H-13¢), 5.35 (d, 1 H, J = 8.2 Hz, H-5), 5.45–5.80 (m, 2 H, H-
7¢ and H-11¢), 5.83 (d, 1 H, J = 4,3 Hz, H-1¢), 7.25–7.75 (m,
10 H, 2 ꢀ Ph), 7.95 (d, 1 H, J = 8.2 Hz, H-6), 8.55 (br s, 1 H,
NH-3) ppm. 13C NMR (100 MHz, CDCl3): d = 18.3
[(CH3)3C-Si], 26.0 [(CH3)3C-Si], 29.6 (C-6¢), 32.3 (C-10¢),
38.3 (C-3¢), 46.4 (C-2¢), 63.5 (C-5¢), 83.1 (C-4¢), 87.8 (C-1¢),
101.2 (C-5), 116.1 (C-8¢), 116.3 (C-12¢), 128.0–135.6 (2 ꢀ
Ph), 129.2 (C-7¢), 129.7 (C-11¢), 139.4 (C-6), 149.3 (C=O),
162.1 (C=O) ppm.
(27) For general reviews, see: (a) Grubbs, R. H.; Chang, S.
Tetrahedron 1998, 54, 4413. (b) Armstrong, S. K. J. Chem.
Soc., Perkin Trans. 1 1998, 371. (c) Fürstner, A. Angew.
Chem. Int. Ed. 2000, 39, 3012. (d) Dieters, A.; Martin, S. F.
Chem. Rev. 2004, 104, 2199; and references cited therein.
(28) For recent examples of RCM in nucleosides field, see:
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(b) Borsting, P.; Freitag, M.; Nielsen, P. Tetrahedron 2004,
60, 10955. (c) Agrofoglio, L. A.; Amblard, F.; Nolan, S. P.;
Charamon, S.; Gillaizeau, I.; Zevaco, T. A.; Guenot, P.
Tetrahedron 2004, 60, 8397. (d) Freitag, M.; Thomassen,
H.; Christensen, N. K.; Petersen, M.; Nielsen, P.
Tetrahedron 2004, 60, 3775. (e) Busca, P.; Etheve-
Quelquejeu, M.; Valéry, J.-M. Tetrahedron Lett. 2003, 44,
9131. (f) Montembault, M.; Bourgougnon, N.; Lebreton, J.
Tetrahedron Lett. 2002, 43, 8091. (g) Ewing, D.; Glaçon,
V.; Mackenzie, G.; Postel, D.; Len, C. Tetrahedron Lett.
2002, 43, 3503. (h) Ewing, D.; Glaçon, V.; Mackenzie, G.;
Postel, D.; Len, C. Tetrahedron 2003, 59, 941.
(34) (a) Oba, M.; Suyama, M.; Shimamura, A.; Nishiyama, K.
Tetrahedron Lett. 2003, 44, 4027. (b) Chu, C. K.; Bhadti, V.
S.; Doboszewski, B.; Gu, Z. P.; Kosugi, Y.; Pullaiah, K. C.;
Van Roey, P. J. Org. Chem. 1989, 54, 2217. (c) Nair, V.;
Buenger, G. S. J. Am. Chem. Soc. 1989, 111, 8502.
(35) Selected physico-chemical data for major diastereomer 19:
Rf = 0.23 (5% EtOH–CH2Cl2). 1H NMR (300 MHz,
CD3COCD3): d = 9.98 (br s, 1 H, NH), 8.30 (d, 1 H, J = 8.1
Hz, H6), 5.76–5.72 (m, 2 H, H7¢ and H8¢), 5.69 (d, 1 H, J = 2.5
Hz, H1¢), 5.54 (d, 1 H, J = 8.1 Hz, H5), 4.38 (br s, 1 H, OH),
3.98 (dd, 1 H, J4¢-5¢ = 2.6 Hz and J5¢-5¢= 12.1 Hz, H5¢), 3.90 (dt,
(29) For radical allylation at C-2¢, see: (a) Stork, G.; Zhang, C.;
Gryaznov, S.; Schultz, R. Tetrahedron Lett. 1995, 36, 6387.
(b) Cicero, D. O.; Neuner, P. J. S.; Franzese, O.; D’Onofrio,
C.; Iribarren, A. M. Bioorg. Med. Chem. Lett. 1994, 7, 861.
(c) De Mesmaeker, A.; Lebreton, J.; Waldner, A.; Fritsch,
V.; Wolf, R. M.; Freier, S. M. Synlett 1993, 733. (d) De
Mesmaeker, A.; Lebreton, J.; Hoffmann, P.; Freier, S. M.
Synlett 1993, 677. (e) Chu, C. K.; Doboszewski, W. S.;
Ullas, G. J. Org. Chem. 1989, 54, 2767. For radical
allylation at C-3¢, see: (f) Rozners, E.; Katkevica, D.;
Bizdena, E.; Strömberg, R. J. Am. Chem. Soc. 2003, 125,
12125. (g) Batoux, N.; Benhaddou-Zerrouki, R.; Bressolier,
P.; Granet, R.; Laumont, G.; Aubertin, A.-M.; Krausz, P.
Tetrahedron Lett. 2001, 42, 1491. (h) De Mesmaeker, A.;
Lesueur, C.; Bévièrre, M.-O.; Waldner, A.; Fritsch, V.;
Wolf, R. M. Angew. Chem., Int. Ed. Engl. 1996, 35, 2790.
(i) Fiandor, J.; Tam, S. Y. Tetrahedron Lett. 1990, 31, 597.
(30) An, H.; Wang, T.; Maier, M. A.; Manoharan, M.; Ross, B.
S.; Cook, P. D. J. Org. Chem. 2001, 66, 2789.
1 H, J4¢-5¢ = 2.6 Hz, J3¢-4¢ = 7.9 Hz, H4¢), 3.82 (dd, 1 H, J4¢-5¢
=
2.6 Hz and J5¢-5¢ = 12.1 Hz, H5¢), 2.56 (m, 1 H, H2¢), 2.54 (m,
1 H, H3¢), 2.43–2.27 (m, 2 H, H6¢eq and H9¢eq), 2.09–1.96 (m,
2 H, H6¢ax and H9¢ax) ppm. 13C NMR (75 MHz, CD3SOCD3):
d = 163.2 (C4), 150.6 (C2), 140.5 (C6), 125.0 (C8¢ or C7¢),
124.3 (C8¢ or C7¢), 100.6 (C5), 89.2 (C1¢), 84.9 (C4¢), 60.5
(C5¢), 40.2 (C2¢), 32.2 (C3¢), 22.9 (C6¢), 22.9 (C9¢) ppm.
HRMS (ESI): m/z calcd for C13H16N2O4Na [M + Na+]:
287.1008; found: 287.1004.
(36) Selected physico-chemical data for minor diastereomer 20:
Rf = 0.26 (5% EtOH–CH2Cl2). 1H NMR (300 MHz,
CD3COCD3): d = 9.98 (br s, 1 H, NH), 8.15 (d, 1 H, J = 8.1
Hz, H6), 5.88 (d, 1 H, J = 7.9 Hz, H1¢), 5.77 (m, 1 H, J = 11.9
Hz, H8¢), 5.71 (m, 1 H, J = 11.9 Hz, H7¢), 5.60 (d, 1 H, J = 8.1
Hz, H5), 4.27 (br s, 1 H, OH), 4.22 (dt, 1 H, J4¢-5¢ = 2.6, 3.3
Hz, J3¢-4¢ = 6.6 Hz, H4¢), 3.89 (dd, 1 H, J4¢-5¢ = 3.3 Hz and
(31) Barton, D. H. R.; Jaszberenyi, J. C. Tetrahedron Lett. 1989,
30, 2619.
(32) Personal communication from Dr. Alain De Mesmaeker
(Syngenta, Basel, Switzerland).
(33) Representative Procedure for the Preparation of 3¢-C-
Allyluridine 25 and 26.
J5¢-5¢ = 11.9 Hz, H5¢), 3.76 (dd, 1 H, J4¢-5¢ = 2.6 Hz and J5¢-5¢
11.9 Hz, H5¢), 2.38–2.28 (m, 2 H, H2¢ and H3¢), 2.28 (m, 1 H,
6¢eq), 2.30–2.20 (m, 2 H, H9¢ax and H9¢eq), 2.00 (m, 1 H, H6¢ax
ppm. 13C NMR (75 MHz, CD3SOCD3): d = 163.0 (C4),
=
H
)
A degassed solution of thiocarbonate 24 (1.0 g, 1.56 mmol),
Bu3SnAll (4.83 mL, 15.58 mmol, 10 equiv), AIBN (256 mg,
1.56 mmol, 1 equiv) and Bu3SnH (45 mg, 0.16 mmol, 0.1
equiv) in distilled benzene (1.5 mL, 1 mol/L) was stirred
overnight at reflux. The solvent was removed under reduced
pressure and purification by flash chromatography (30%
Et2O–PE) afforded a mixture of diastereoisomers 25 and 26
(420 mg, 51%) as a white foam; 75% de [determined by
HPLC performed using a Chrompack Inertsil column
Intersil 250 ꢀ 3 mm with a flow of rate 1 mL/min (CH2Cl2),
150.8 (C2), 140.6 (C6), 126.8 (C8¢), 125.7 (C7¢), 101.8 (C5),
87.5 (C1¢), 79.7 (C4¢), 61.6 (C5¢), 42.9 (C2¢), 40.6 (C3¢),
26.8 (C6¢), 25.3 (C9¢) ppm. HRMS (ESI): m/z calcd for
C13H16N2O4Na [M + Na+]: 287.1008; found: 287.0995.
(37) Preparative HPLC was performed using a Chrompack
Inertsil column Intersil 250 ꢀ 10 mm with a flow of rate 1
mL/min (CH2Cl2–MeOH, 95:5) with tR = 31.0 min for minor
diastereomer 20 and tR = 34.8 min for major diastereomer
19.
Synlett 2006, No. 9, 1339–1342 © Thieme Stuttgart · New York