Efficient synthesis of sugar iminopyrrolidine derivatives via an intramolecular Staudinger-aza-Wittig-type reaction

Article abstract of DOI:10.1055/s-2006-948177

We report herein the first example of a Staudinger-aza-Wittig-type reaction on a substituted furanoside in which a β-azido glyco-α-aminonitrile was converted into fused iminopyrrolidines in good yields, and the following hydrolysis gave the corresponding conformationally restricted glycoamino acids. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-948177

LETTER
1875
Efficient Synthesis of Sugar Iminopyrrolidine Derivatives via an
Intramolecular Staudinger–aza-Wittig-Type Reaction
S
ynthesis of Sugar
é
Iminopyrr
l
è
Derivativesne Ducatel,a Albert Nguyen Van Nhien,a Serge Pilard,b Denis Postel*a
a
Laboratoire des Glucides (UMR 6219), Faculté des Sciences, Université de Picardie Jules Verne, 33 rue Saint Leu, 80039 Amiens, France
Fax +33(3)22827568; E-mail: denis.postel@u-picardie.fr
b
Plateforme Analytique, Université de Picardie Jules Verne, Faculté des Sciences, 33, rue Saint Leu, 80039 Amiens, France
Received 16 March 2006
ly explored,8c in contrast to a much more intensive inves-
tigation of similar chemistry on the carbonyl group. Of
particular note in respect of the latter is the Staudinger–
aza-Wittig reaction, which involves a one-pot N3 reduc-
tion and subsequent addition of the amino group to a car-
bonyl to give a cyclic imine as exemplified recently by
Spagnolo and coworkers who described a radical reaction
of Bu3SnH with azidonitriles. This involved a 5-exo cy-
clization onto the cyano moiety to give an aminoiminyl
radical that was reduced to give an amidine.9
Our interest in the chemistry of glyco-a-aminonitriles10
and their use in heterocyclic chemistry prompted us to ex-
plore the feasibility of the Staudinger–aza-Wittig reaction
to enable a one-pot 5-exo cyclization of an azido nitrile to
provide a sugar amidine.
Abstract: We report herein the first example of a Staudinger–aza-
Wittig-type reaction on a substituted furanoside in which a b-azido
glyco-a-aminonitrile was converted into fused iminopyrrolidines in
good yields, and the following hydrolysis gave the corresponding
conformationally restricted glycoamino acids.
Key words: aza-sugars, Wittig reactions, glycoamino nitrile,
glycoamino acids, iNOS
Nitric oxide (NO) is an endogenous chemical mediator
that plays a role in various physiological processes, such
as endothelium-dependent vasodilatation, cell-to-cell
communication and cytotoxicity of phagocytes.1 Three
isoforms of nitric oxide synthase are involved in the NO
biosynthesis which includes the nNOS and eNOS consti-
tutive forms and iNOS inducible form.2 The inducible
NOS (iNOS) gene is expressed as a result of stimulation
by inflammatory cytokines and is an important compo-
nent in the body’s immune defense. During inflammation,
the iNOS enzyme is expressed in many tissues and pro-
duces NO at levels 1,000 times greater than nNOS or
eNOS and in fact represents a major contributor to the
patholophysiology of many human diseases.3 Many dif-
ferent types of NOS inhibitors which have been described
in the past few years have focused on structural analogues
of L-arginine including either the guanidine or amidine
moieties.4 Since 1996, 2-iminoazaheterocycles have been
reported to be potent inhibitors of NOS. This series
included cyclic amidines ranging from five- to nine-mem-
bered rings, of which 2-iminopiperidine and 2-homopipe-
ridine were the most potent inhibitors for human inducible
nitric oxide synthase and the parent iminopyrrolidine ring
was a modest inhibitor of hiNOS.5,6a–c Several synthetic
methods have been used to synthesize iminopyrrolidine
rings, one of which involved a lactam as a key intermedi-
ate. This heterocyclic intermediate gave the amidine via
an iminoether using trimethyloxonium tetrafluoroborate,
by treatment with sulfuryl chloride isocyanate7 or through
conversion of the carbonyl into a thiocarbonyl group and
subsequent treatment with an amine and HgCl2.8a,8b Sur-
prisingly, the route which consists of nucleophilic addi-
tion of an amino group on the electrophilic carbon of a
cyano or imino group appears not to have been extensive-
In this paper, we report our initial results of the treatment
of various a-substituted g-azido nitriles with either Ph3P
or Me3P in THF.
The glycoderivatives 3 and 4 were each synthesized in
87% yield by stereoselective aminocyanation of the ulose
(1)11 using NH3–MeOH/TMSCN/Ti(Oi-Pr)4 (49%) fol-
lowed by classical mesylation or acetylation, respectively
(Scheme 1).
N3
N3
N3
O
O
O
O
O
O
i
iii
NC
RHN
NC
RO
O
O
O
O
1
2 R = H (49%)
3 R = Ms (87%)
4 R = Ac (quant.)
5 R = H (85%)
6 R = Ms (74%)
7 R = Ac (67%)
ii
iv
ii
iv
Scheme 1 Reagents: (i) a) Ti(Oi-Pr)4, MeOH–NH3 7 N; b)
TMSCN; (ii) MsCl, DMAP, pyridine; (iii) NaHCO3, KCN, H2O–
Et2O; (iv) Ac2O, pyridine.
Treatment of 1 with NaCN and NaHCO3 in biphasic H2O–
Et2O media gave the ribo-cyanohydrine 5 in 85% yield
which upon subsequent mesylation and acetylation
accordingly gave the corresponding derivatives 6 (74%)
and 7 (67%).
Treatment of 2 using classical Staudinger conditions
(Me3P–THF) for one hour gave quantitatively the hetero-
cyclic iminopyrrolidine 8 and iminophosphorane inter-
mediate 9 with inseparable traces of (Me)3P=O (Figure 1).
Longer treatment with NH3–MeOH allowed quantitative
conversion of 9 into the final compound 8 (Figure 1).
SYNLETT 2006, No. 12, pp 1875–1878
0
1
.0
8
.2
0
0
6
Advanced online publication: 24.07.2006
DOI: 10.1055/s-2006-948177; Art ID: D08106ST
© Georg Thieme Verlag Stuttgart · New York

1876
H. Ducatel et al.
LETTER
The functionalized aminonitriles 3 and 4 reacted similarly
to the unsubstitued compound 2, to give the correspond-
ing cyclic pyrrolidines 12 and 13 in 76% and 77% yields,
respectively.
H
O
H
O
O
O
N
N
O
O
NH2
NH2
N
NH2
PMe3
8
9
Contrary to the amino derivatives, the reactivity of the
cyanohydrin seemed to be conditioned by the nature of the
O-substituent.
Figure 1
Starting from 5, the corresponding amidine 10 was
formed in 69% yield (isolated as the corresponding
acetylated amidine 11). Surprisingly, the aza-Wittig reac-
tion failed with the functionalized derivatives 6 and 7.
Treatment of acetylated 7 with either PPh3 or PMe3 gave
exclusively the Staudinger reaction product 14 in 55–64%
yield. The Staudinger reaction was also observed with
PPh3 and the mesylated cyanohydrine 6, but in this case
the reduced amino derivative 15 was unstable and could
not be isolated.
Compounds 8 and 913 were characterized by NMR
spectroscopy and mass spectrometry (8: m/z = 214.12
[M – H+]; 9: m/z = 288.14 [M – H+]).
The use of triphenylphosphine instead of Me3P allowed
convenient removal of the triphenylphospine oxide during
the work-up (Et2O–H2O) to afford 8 in 89% yield after
five hours.12
In order to study the role of the a-substituent in the aza-
Wittig reaction, these conditions were applied to the
cyanohydrine 5 and the N- (or O-) substituted derivatives
3, 4, 6 and 7 (Table 1).
The use of the more basic trimethylphosphine instead of
PPh3 led to the heterocyclic compound 16 (76%) resulting
from a Staudinger reduction and subsequent intramole-
cular carbanionic cyclization (CSIC reaction)10d between
the mesyl and the cyano groups.
Table 1 Reaction of N- (or O-) Substituted Derivatives 3, 4, 6 and
7 with Phosphine
These results demonstrated that the Staudinger–aza-
Wittig reaction seems to be independent of the electrone-
gativity of the heteroatom in the a-position but should be
ineffective when the a-substituent is an oxygenated elec-
tron-withdrawing group. In this case, the product resulted
in a Staudinger reduction.
Substrate
Phosphine Yield (%)
Reaction product
H
O
N3
O
O
O
N
NC
MsHN
3
PPh3
PPh3
PMe3
76
77
69
O
O
NHMs
NH2
12
With a view to obtaining a convenient route to glyco-
diaminoacids (GDAs), the iminopyrrolidine 8 was hydro-
lyzed in a refluxing basic aqueous media using NaOH (2
N; Scheme 2).
H
O
N3
NC
AcHN
O
O
O
O
N
O
O
NHAc
NH2
The reaction proceeded via an a-amino lactam intermedi-
ate (17)14 to give the GDA 1815 quantitatively after 48
hours.
4
13
H
O
N3
NC
HO
O
O
N
O
H
O
OH
NH2
O
H2N
O
O
O
5
8
HOOC
HN
10
O
O
NH2
H2N
O
H2N
NC
AcO
O
O
N3
O
O
O
17
18
O
PPh3
PMe3
55
64
NC
AcO
O
O
Scheme 2 Reagents and conditions: H2O–NaOH (2 N), reflux; then
IRA-120.
14
7
N3
H2N
The lactam intermediate 17 was isolated using a lower
NaOH concentration (0.1 N vs. 2 N) in 49% yield after 12
hours.
O
O
NC
MsO
NC
MsO
O
O
6
PPh3
–
15
Similarly, this route was applied to the synthesis of the
pseudodisaccharide 22 (Scheme 3). Treatment of 20 with
Ph3P in THF gave the amidine 2116 in 80% yield. Subse-
quent hydrolysis with NaOH (2 N) and then with acidic
resin (Amberlite IRA-120) led, quantitatively, to the
corresponding bis-glycoamino acid in which the pseudo-
disaccharidic linkage is the a-amino acid function.17
H2N
O
O
H2N
O
O
S
O
O
PMe3
76
16
Synlett 2006, No. 12, 1875–1878 © Thieme Stuttgart · New York

LETTER
Synthesis of Sugar Iminopyrrolidine Derivatives
1877
H2N
O
H
H
O
O
H2N
HO
N3
NC
HN
O
O
O
O
O
O
N
O
19
O
O
O
HN
HN
iii
ii
i
HO
H2N
O
O
O
1
O
O
O
HO
HO
HO
O
O
O
20
21
22
Scheme 3 Reagents and conditions: (i) a) 19, Ti(Oi-Pr)4, MeOH, b) TMSCN; (ii) a) PPh3, THF, b) NH3–MeOH; (iii) H2O–NaOH (2 N),
reflux; then IRA-120.
M.; Humes, J. L.; Pacholok, S. G.; Kelly, T. M.; Grant, S. K.;
Wong, K. K. Bioorg. Med. Chem. Lett. 2004, 14, 5907.
(c) Gadreau, C.; Foucaud, A. Tetrahedron Lett. 1974, 48,
4243.
In conclusion we reported the first example of a
Staudinger–aza-Wittig reaction on a furanoside, which
gave a convenient access to fused iminopyrrolidines in
good yields. Further experiments are in progress to ex-
plore the influences of the substituent in the a-position re-
garding the electronic effect and the hard and soft balance
between the N-nucleophilic center of the iminophospho-
rane and C-electrophilic center of the cyano group.
(9) Benati, L.; Bencivenni, G.; Leardini, R.; Minozzi, M.;
Nanni, D.; Scialpi, R.; Spagnolo, P.; Zanardi, G.; Rizzoli, C.
Org. Lett. 2004, 6, 417.
(10) (a) Postel, D.; Nguyen Van Nhien, A.; Pillon, M.; Villa, P.;
Ronco, G. Tetrahedron Lett. 2000, 41, 6403. (b) Nguyen
Van Nhien, A.; Ducatel, H.; Len, C.; Postel, D. Tetrahedron
Lett. 2002, 43, 3805. (c) Postel, D.; Nguyen Van Nhien, A.;
Marco, J. L. Eur. J. Org. Chem. 2003, 19, 3713.
(d) Dominguez, L.; Nguyen Van Nhien, A.; Tomassi, C.;
Len, C.; Postel, D.; Marco-Contelles, J. L. J. Org. Chem.
2004, 69, 843. (e) Nguyen Van Nhien, A.; Tomassi, C.; Len,
C.; Marco-Contelles, J. L.; Balzarini, J.; Pannecouque, C.;
De Clercq, E.; Postel, D. J. Med. Chem. 2005, 48, 4276.
(11) Ewing, D. F.; Goethals, G.; MacKenzie, G.; Martin, P.;
Ronco, G.; Vanbaelinghem, L.; Villa, P. Carbohydr. Res.
1999, 321, 190.
Acknowledgment
The authors thank the Conseil Régional de Picardie and the Mini-
stère Français de la Recherche for supporting this work and to G.
Mackenzie for helpful discussions, and careful revision of the
manuscript.
References and Notes
(12) (1R,3R,4R,5R)-5,6-Diamino-3,4-O-isopropylidene-7-aza-
2-oxabicyclo[3.3.0]oct-6-ene (8).
(1) Moncada, S.; Higgs, E. A. FASEB J. 1995, 9, 1319.
(2) Knowles, R. G.; Moncada, S. Biochem. J. 1994, 298, 249.
(3) Kawanaka, Y.; Kobayashi, K.; Kusuda, S.; Tatsumi, T.;
Murot, M.; Nishiyama, T.; Hisaichi, K.; Fujii, A.; Hirai, K.;
Nak, M.; Komeno, M.; Odagaki, Y.; Nakai, H.; Toda, M.
Bioorg. Med. Chem. Lett. 2003, 13, 1723; and references
cited therein.
(4) (a) Ueda, S.; Terauchi, H.; Yano, A.; Iro, M.; Matsumoto,
M.; Kawasaki, M. Bioorg. Med. Chem. Lett. 2004, 14, 313.
(b) Atkinson, R. N.; Moore, L.; Tobin, J.; King, S. B. J. Org.
Chem. 1999, 64, 3467.
(5) Moore, W. M.; Webber, R. K.; Fok, K. F.; Jerome, G. M.;
Connor, J. R.; Manning, P. T.; Wyatt, P. S.; Misko, T. P.;
Tjoeng, F. S.; Currie, M. G. J. Med. Chem. 1996, 39, 669.
(6) (a) Hagen, T. J.; Bergmanis, A. A.; Kramer, S. W.; Fok, K.
F.; Schmelzer, A. E.; Pitzele, B. S.; Swenton, L.; Jerome, G.
M.; Kornmeier, C. M.; Moore, W. M.; Branson, L. F.;
Connor, J. R.; Manning, P. T.; Currie, M. G.; Hallinan, E. A.
J. Med. Chem. 1998, 41, 3675. (b) Tsymbalov, S.; Hagen,
T. J.; Moore, W. M.; Jerome, G. M.; Connor, J. R.; Manning,
P. T.; Pitzele, B. S.; Hallinan, E. A. Bioorg. Med. Chem. Lett.
2002, 12, 3337. (c) Guthikonda, N. R.; Shah, S. K.;
Pacholok, S. G.; Humes, J. L.; Mumford, R. A.; Grant, S. K.;
Chabin, R. M.; Green, B. G.; Tsou, N.; Ball, R.; Fletcher, D.
S.; Luell, S.; MacIntyre, D. E.; MacCoss, M. Bioorg. Med.
Chem. Lett. 2005, 15, 1997.
To a solution of compound 2 (0.20 g, 0.85 mmol) in 10 mL
of THF–H2O (4:1) was added 0.25 g (0.93 mmol) of PPh3.
After stirring overnight at r.t., the reaction mixture was
evaporated and extracted with Et2O and H2O. The aqueous
layer was evaporated to give 0.16 g (89%) of 8 as a slight
yellow syrup; [a]D20 20 (c 0.17, CHCl3). IR (ATR): 2988,
1655, 1374, 1217, 1165, 1086, 1007, 877, 733 cm–1. 1H
NMR (CDCl3): d = 5.80 (d, 1 H, H-1, J1,2 = 3.9 Hz), 4.60 (d,
1 H, H-2), 4.30 (d, 1 H, H-4, J4,5a = 3.0 Hz), 3.72 (dd, 1 H,
H-5a, J5a,5b = 14.0 Hz), 3.67 (d, 1 H, H-5b), 1.53 (s, 3 H,
CH3), 1.35 (s, 3 H, CH3). 13C NMR (CDCl3): d = 168.2
(C=N), 112.9 (CH3CCH3), 106.1 (C-1), 85.1 (C-4), 82.2
(C-2), 74.1 (C-3), 55.5 (C-5), 27.6, 27.3 (2 × CH3). HRMS:
m/z calcd for C9H16N3O3 [M + H]+: 214.1192; found:
214.1196. Anal. Calcd for C9H15N3O3: C, 50.69; H, 7.09; N,
19.71. Found: C, 50.54; H, 6.95; N, 19.60.
(13) Key Data for Compound 9.
13C NMR (CDCl3): d = 173.4 (C=N, J2C-P = 9.0 Hz), 75.4
(C-3, J3C-P = 17.2 Hz), 14.4 [P(CH3)3, J1CH3-P = 66.0 Hz).
MS: m/z = 288.14 [M + H]+.
(14) 3-Amino-3-deoxy-1,2-O-isopropylidene-a-D-ribofurano-
sidurono-3,5-lactam (17).
White solid, mp 159–162 °C; [a]D20 18 (c 0.11, CHCl3). 1H
NMR (CD3OD): d = 5.81 (d, 1 H, H-1, J1,2 = 3.9 Hz), 4.60
(d, 1 H, H-2), 4.40 (d, 1 H, H-4, J4,5a = 3.5 Hz), 3.65 (dd, 1
H, H-5a, J5a,5b = 11.8 Hz), 3.32 (d, 1 H, H-5b), 1.56 (s, 3 H,
CH3), 1.38 (s, 3 H, CH3). 13C NMR (CD3OD): d = 176.4 (1
C, C=O), 112.8 (1 C, CH3CCH3), 106.1 (1 C, C-1), 81.9 (1
C, C-2), 81.8 (1 C, C-4), 68.8 (1 C, C-3), 45.6 (1 C, C-5),
26.4, 26.0 (2 C, CH3). IR (ATR): n = 2959, 2932, 1716,
1659, 1465, 1382, 1233, 1166, 1098, 1082, 1001 cm–1.
HRMS: m/z calcd for C9H14N2O4Na: 237.0851 [M + Na]+;
found: 237.0850.
(7) Burden, P. M. Synth. Commun. 1993, 23, 1195.
(8) (a) Shankaran, K.; Donnelly, K.; Shah, S. K.; Guthikonda, R.
N.; MacCoss, M.; Humes, J. L.; Pacholok, S. G.; Grant, S.
K.; Kelly, T. M.; Wong, K. K. Bioorg. Med. Chem. Lett.
2004, 14, 4539. (b) Shankaran, K.; Donnelly, K. L.; Shah, S.
K.; Caldwell, C. G.; Chen, P.; Hagmann, W. K.; MacCoss,
Synlett 2006, No. 12, 1875–1878 © Thieme Stuttgart · New York

1878
H. Ducatel et al.
LETTER
(15) 3,5-Diamino-3-C-carboxy-3,5-dideoxy-1,2-O-isopropyl-
idene-a-D-ribofuranose (18).
(2 C, 2 C-1), 85.6 (1 C, C-2), 83.1 (1 C, C-4), 82.2 (1 C, C-
2¢), 77.9 (1 C, C-4¢), 76.5 (2 C, C-3¢, C-3), 58.2 (1 C, C-5¢),
42.4 (1 C, C-5), 27.3 (1 C, CH3), 27.1 (1 C, CH3), 26.7 (1 C,
CH3), 26.1 (1 C, CH3). HRMS: m/z calcd for C17H28N3O7:
386.1927 [M + H]+; found: 386.1908. Anal. Calcd for
C17H27N3O7: C, 52.98; H, 7.06; N, 10.90. Found: C, 52.91;
H, 7.04; N, 10.87.
White solid, mp 200 °C; [a]D20 77 (c 0.21, H2O). 1H NMR
(D2O): d = 5.88 (d, 1 H, H-1, J1,2 = 3.6 Hz), 4.55 (d, 1 H, H-
2), 3.94 (dd, 1 H, H-4, J4,5a = 1.8 Hz), 3.13 (dd, 1 H, H-5a,
J5a,5b = 13.3 Hz), 2.78 (dd, 1 H, H-5b, J5b,4 = 9.9 Hz), 1.44 (s,
3 H, CH3), 1.27 (s, 3 H, CH3). 13C NMR (D2O): d = 175.1
(1 C, C=O), 113.4 (1 C, CH3CCH3), 105.9 (1 C, C-1), 83.3
(1 C, C-2), 80.3 (1 C, C-4), 68.5 (1 C, C-3), 40.1 (1 C, C-5),
26.1, 25.7 (2 C, CH3). IR (ATR): n = 2987, 2917, 1614,
1540, 1409, 1381, 1230, 1163, 1069, 1015, 883, 809 cm–1.
HRMS: m/z calcd for C9H16N2O5Na: 255.0957 [M + Na]+;
found: 255.0950.
(17) 3,5-Diamino-3-C-carboxy-3,5-dideoxy-3-N-[1¢,2¢-O-
isopropylidene-a-D-xylofuranos-5¢-yl]-1,2-O-isopropyl-
idene-a-D-ribofuranose (22).
White solid, mp 254–256 °C; [a]D25 8.0 (c 0.21, CHCl3). IR
(ATR): 2987, 2900, 1589, 1394, 1215, 1066 cm–1. 1H NMR
(CD3OD): d = 5.99 (d, 1 H, H-1¢, J1¢,2¢ = 3.6 Hz), 5.95 (d, 1
H, H-1, J1,2 = 3.8 Hz), 5.01 (d, 1 H, H-2), 4.49 (d, 1 H, H-2¢),
4,22 (m, 2 H, H-4¢, H-3¢), 3.98 (t, 1 H, H-4, J4,5 = 6.8 Hz),
3.12 (d, 2 H, H-5), 3.56 (dd, 2 H, H-5a¢, J5a,5b = 11.7 Hz,
(16) (1R,3R,4R,5R)-5-{[1,2-O-Isopropylidene-a-D-xylo-
furanos-5-yl]amino}-6-amino-3,4-O-isopropylidene-7-
aza-2-oxabicyclo[3.3.0]oct-6-ene (21).
White solid, mp 125–128 °C; [a]D20 18.2 (c 0.36, CHCl3). IR
(ATR): 2989, 2901, 1655, 1384, 1217, 1167, 1073, 1014,
879, 858 cm–1. 1H NMR (CDCl3): d = 5.89 (d, 1 H, H-1,
J5a,4 = 6.3 Hz), 2.71 (dd, 1 H, H-5b¢, J5b,4 = 7.3 Hz), 1.56 (s,
3 H, CH3), 1.47 (s, 3 H, CH3), 1.38 (s, 3 H, CH3), 1.31 (s, 3
H, CH3). 13C NMR (CD3OD): d = 174.6 (1 C, C=O), 112.3,
111.6 (2 C, CH3CCH3), 106.8, 105.4 (2 C, C-1¢, C-1), 85.2
(1 C, C-2¢), 81.2 (1 C, C-2), 80.8 (1 C, C-4¢), 77.8 (1 C, C-
4), 76.5 (2 C, C-3¢, C-3), 43.1 (1 C, C-5¢), 40.9 (1 C, C-5),
26.4 (1 C, CH3), 26.2 (1 C, CH3), 25.7 (1 C, CH3), 25.5 (1 C,
CH3). HRMS: m/z calcd for C17H28N2O9Na: 427.1693
[M + Na]+; found: 427.1685.
J
1,2 = 3.6 Hz), 5.77 (d, 1 H, H-1¢, J1¢,2¢ = 3.7 Hz), 4.62 (d,
1 H, H-2¢), 4.52 (s, 1 H, H-4), 4.38 (d, 1 H, H-2), 4.14 (d, 1
H, H-4¢, J4¢,3¢ = 2.7 Hz), 4.05 (d, 1 H, H-3¢), 3.56 (s, 2 H, H-
5¢), 3.06 (d, 1 H, H-5a, J5a,5b = 11.7 Hz), 2.77 (dd, 1 H, H-5b,
J
5b,4 = 3.5 Hz), 1.48 (s, 3 H, CH3), 1.39 (s, 3 H, CH3), 1.29
(s, 3 H, CH3), 1.20 (s, 3 H, CH3). 13C NMR (CDCl3): d =
164.9 (1 C, CN), 112.9, 111.5 (2 C, CH3CCH3), 105.2, 104.8
Synlett 2006, No. 12, 1875–1878 © Thieme Stuttgart · New York