Synthesis of α- and β-C-glycosides of N-acetylglucosamine

Article abstract of DOI:10.1016/S0040-4039(03)00818-9

As part of efforts to make available new classes of bioactive C-glycoconjugates, D-glucosamine has been effectively converted into a series of 2-deoxy-2-amino-C-glycosides. This versatile approach is keyed by a remarkably effective metal catalyzed olefin isomerization of the isomeric C-allyl amino sugars which, in turn, are readily available via radical allylation of D-glucosamine.

Full text of DOI:10.1016/S0040-4039(03)00818-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 3775–3779
Synthesis of a- and b-C-glycosides of N-acetylglucosamine
Glenn J. McGarvey,* Frank W. Schmidtmann, Tyler E. Benedum and Darin E. Kizer
Department of Chemistry, University of Virginia, Charlottesville, VA 22903, USA
Received 23 January 2003; revised 18 March 2003; accepted 18 March 2003
Abstract—As part of efforts to make available new classes of bioactive C-glycoconjugates,
D-glucosamine has been effectively
converted into a series of 2-deoxy-2-amino-C-glycosides. This versatile approach is keyed by a remarkably effective metal
catalyzed olefin isomerization of the isomeric C-allyl amino sugars which, in turn, are readily available via radical allylation of
D
-glucosamine. © 2003 Elsevier Science Ltd. All rights reserved.
Cell surface glycoconjugates provide an information
rich matrix that mediates cellular interactions with
other cells and with extracellular components. In this
context, glycoproteins have been shown to be relevant
in numerous important disease states.1 The protein is
typically conjugated to a carbohydrate moiety through
a 2-deoxy-2-amino sugar, including both a- and b-
linked glucosamine and galactosamine (examples in
Figure 1). The carbohydrate epitopes of these conju-
gates have been shown to play a central role in a
variety of significant biological events, including
immune response, inflammation, metastasis, and bacte-
rial and viral infection, among others.2 There is consid-
erable interest in developing effective therapeutic
strategies based upon recognition of these cell surface
carbohydrates.
Studies to understand the structural features of cellular
communication and to develop stable carbohydrate-
based therapeutic agents have been complicated by the
intrinsic lability of the N- or O-acetal linkages between
the carbohydrate and its bioconjugate. An intriguing
approach to the solution of this problem lies in the
replacement of the exocyclic heteroatom with a carbon
to afford C-glycosidic analogues that are impervious to
degradation by glycosidases (i.e. X=carbon linkage in
Figure 1). This has focused considerable attention on
the synthesis and properties of these unnatural
analogues.3
Despite structural investigations that have revealed
notable conformational differences between the natural
and unnatural glycosides,4 largely attributed to the
exo-anomeric effect,5 a number of studies comparing
the natural O-glycosides with their C-glycoside ana-
logues in biological settings have shown that the biolog-
ical properties of the carbohydrates are retained.6 Two
recent reports are particularly relevant to the present
studies. In one, a peptide fragment of type II collagen
incorporating a C-glycoside analogue of b-D-galactosyl
hydroxyvaline was evaluated for its immunogenicity
versus helper T-cell hybridomas obtained from a mouse
model for rheumatoid arthritis and was found to be
active, albeit at higher concentrations than the corre-
sponding natural O-glycopeptide.7 In another study, an
exact C-glycoside of a glucosamine glycerolipid was
found to display virtually identical antiproliferative
activity to the O-glycosidic analogue.8
Figure 1. Representative glycopeptide structures.
* Corresponding author.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00818-9

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G. J. McGar6ey et al. / Tetrahedron Letters 44 (2003) 3775–3779
Figure 2 with the expectation that our results would
translate to other 2-amino carbohydrate substrates.
Application of the radical allylation procedures
reported by Horton12 and Bertozzi13 allowed the prepa-
ration of the a- and b-anomers of acetate protected
C-allyl glucosamine (a-1 and b-1, R=Ac, Scheme 1) in
serviceable yields and quantities. Following a protecting
group exchange (R=Ac“R=Bn), the desired propar-
gyl glycosides, a-2 and b-2, were efficiently obtained by
routine oxidative double bond cleavage14 followed by
exposure to Ohira’s reagent.15 Though synthetically
unremarkable, this route provides a suitable solution to
the lack of direct propargylation methodology.16
Figure 2.
Toward expanding the repertoire of available C-gly-
cosides, we examined metal-catalyzed isomerization of
these allyl species. Following the report of Wong and
co-workers,17 the benzyl-protected a-isomer, a-1, was
exposed to 40 mol% PdCl2 in refluxing benzene for 24
h to afford a 65% yield of the pure disubstituted olefin
a-3 following careful column chromatography (entries
1, Table 1). In the course of efforts to improve the
availability of this valuable intermediate, we observed
that the isomerization could be effected more rapidly
and under much milder conditions using the cationic
Scheme 1. Reagents and conditions: (a) NaOMe, MeOH. (b)
BnBr, NaH, DMF, rt. (c) OsO4, NaIO4, THF/H2O, rt. (d)
MeCOC(N2)P(O)(OMe)2, K2CO3, MeOH, rt.28
iridium catalyst, (PhMe2P)2IrCOD+PF6 (entries 2,
−
Table 1).18 Further studies revealed that the yield of the
desired isomer was significantly improved by decreasing
the amount of catalyst (entries 3–5, Table 1). In addi-
tion, it was noted that extension of the reaction times
had a deleterious effect on the yield of the product,
perhaps as a consequence of over isomerization. Signifi-
cantly, the isomerization of the analogous peracetylated
substrate could be effected as well, though longer reac-
tion times were required and some anomeric epimeriza-
tion was noted (entries 6, Table 1). Guided by these
results, we chose 10 mol% of the catalyst as the stan-
dard conditions to effect this isomerization. It was
gratifying to find that these conditions could be success-
fully applied to the b-anomer as well to afford both
benzyl and acetate protected vinyl glycosides b-3
With such encouraging results as a backdrop, we have
embarked on studies directed toward understanding
and exploiting recognition events based upon cell sur-
face glycoproteins using stable C-glycoside analogues.9
Toward this objective, we sought to develop general
accessibility to a range of stereoisomeric 2-deoxy-2-
amino-C-glycosides that may be used to access C-gly-
copeptide structures related to the types shown in
Figure 1. The preparation of C-glycosides of 2-amino
sugars has proven difficult and, consequently, there are
relatively few methods reported.10,11 We initially
focused our attention on the preparation of the olefinic
and acetylenic derivatives of glucosamine shown in
Table 1.
Entries
Substrate (R)
Catalyst
Mol%
Time (h)
a-3:b-3
Yield (%)
1a
2
3
4
5
6
7
8
a-1 (Bn)
a-1 (Bn)
a-1 (Bn)
a-1 (Bn)
a-1 (Bn)
a-1 (Ac)
b-1 (Bn)
b-1 (Ac)
PdCl2
40
40
20
10
5
10
10
10
24
2.5
2
2
2
20
2
20
100:0
100:0
100:0
100:0
100:0
10:1
65
65
67
87
86
92
60
80
(Ph2Me)2IrCOD·PF6
(Ph2Me)2IrCOD·PF6
(Ph2Me)2IrCOD·PF6
(Ph2Me)2IrCOD·PF6
(Ph2Me)2IrCOD·PF6
(Ph2Me)2IrCOD·PF6
(Ph2Me)2IrCOD·PF6
0:100
1:6
a Carried out in refluxing PhH.28

G. J. McGar6ey et al. / Tetrahedron Letters 44 (2003) 3775–3779
3777
Figure 3.
variety of conditions including the Lemieux conditions,
dihydroxylation (K2OsO4·H2O, K3Fe(CN)6)/oxidative
cleavage (Pb(OAc)4), and ozonolysis, with the latter
giving the desired aldehyde a-4 in >90% yield as judged
by NMR analysis of the crude product.21 This interme-
diate could be processed to the axial ester in a similar
manner (65% overall). Analogous to a report by Bed-
narski and co-workers,22 epimerization of this aldehyde
to the b-isomer could be effected using mild base to
afford a 4:1 mixture of anomers favoring b-4, thus
offering synthetic entre´e to both C-glycosides anomers
from a single intermediate, a-3. An even more expedi-
tious means to the a-methyl ester could be realized
through ozonolysis using Marshall’s protocol.23
Scheme 2. Reagents and conditions: (a) OsO4, NaIO4, THF/
H2O, rt. (b) NaClO2, NaHPO4, 2-methyl-2-butene, THF/
iPrOH, rt. (c) TMSCHN2, MeOH/PhH, rt. (d) O3, CH2Cl2;
Ph3P. (e) K2CO3, CH2Cl2/MeOH (1a:4b). (f) O3, MeOH,
NaOH.28
Aldehydes a-4 and b-4 appeared to be attractive inter-
mediates for the preparation of the targeted vinylic and
acetylenic C-glycosides (see Figure 2). The configura-
tionally stable b-anomer could be straightforwardly
transformed into the corresponding alkynyl b-615 and
vinyl derivatives b-7 using standard methodology,
albeit in modest overall yields from b-3 (Scheme 3).
However, the configurational lability of the a-aldehyde
proved problematic and prompted a broader investiga-
tion. Treatment of aldehyde a-4 with the Ohira
reagent15 led to significant isomerization (53% of a 1:1
mixture of a:b acetylenes) and the application of the
TMSCHN2 methodology24 led to unacceptably poor
yields (15%). Fortunately, the Corey–Fuchs protocol
led to the desired alkyne a-6 in acceptable overall yield
from olefin a-3 as a single isomer.25 Olefination of
aldehyde a-4 to provide vinyl derivative a-7 also proved
troublesome being plagued by epimerization and low
yields. As indicated, standard Wittig olefination gave
the olefin in poor yield, as did a variety of titanium-
mediated olefinations.26 A modest improvement in the
overall yield to this vinyl compound could be realized
through semi-reduction of the acetylene a-6.
Scheme 3. Reagents and conditions: (a) OsO4, NaIO4, THF/
H2O, rt. (b) AcC(N2)P(O)(OMe)2, K2CO3, MeOH, rt. (c)
Ph3PꢀCH2, THF, 0°C. (d) O3, CH2Cl2; Ph3P. (e) CBr4, Ph3P,
CH2Cl2, rt. (f) LDA (4 equiv.), THF, −78°C. (g) H2, Pd on
BaSO4, PhH.28
(entries 7 and 8, Table 1), albeit in somewhat lower
yields and with more isomerization accompanying the
formation of the acetate product.
The configurational lability of the a-aldehyde prompted
a more detailed study of the methods by which the
vinyl C-glycosides could be accessed. An effective solu-
tion is illustrated in Figure 3, wherein olefin metathesis
of the propenyl glycoside a-3 with ethylene using 20
mol% of Grubb’s second generation catalyst 8 afforded
the target vinyl glycoside a-7 in high yield with no
discernible loss of stereochemistry.27 At the end of 48 h,
this metathesis had proceeded to about 90% comple-
tion, thus requiring a second exposure to the metathesis
conditions to effect complete conversion. In this man-
ner, the acetate protected vinyl glycoside becomes avail-
With isomeric vinyl glycosides a-3 and b-3 in hand,
access to additional C-glycosidic derivatives was
explored. Oxidative cleavage of b-vinyl glycoside b-3
using Lemieux conditions14 cleanly afforded the
unstable equatorial aldehyde b-4 that, without purifica-
tion, could be oxidized19 and methylated20 to yield the
b-methyl ester b-5 in good overall yield (Scheme 2).
Likewise, oxidation of the a-3 was examined under a

3778
G. J. McGar6ey et al. / Tetrahedron Letters 44 (2003) 3775–3779
able in 82% overall yield in two steps from the allyl
glycoside a-1. Attempts to expand this approach to the
b-isomer, b-3, were not met with similar success as
ethylene metathesis proceeded to only ꢀ70% conver-
sion under the same conditions.
8. Yang, J.; Franck, R. W.; Bittman, R.; Samadder, P.;
Arthur, G. Org. Lett. 2001, 3, 197–200.
9. McGarvey, G. J.; Benedum, T. E.; Schmidtmann, F. W.
Org. Lett. 2002, 4, 3591–3594.
10. For a recent review: Dondoni, A.; Marra, A. Chem. Rev.
2000, 100, 4395–4421.
In summary, we have demonstrated synthetic accessibil-
ity to a variety of glucosamine C-glycosides that
promise to prove useful in the preparation of novel
C-glycoconjugates. It is further anticipated that the
present methods will be readily extended to other 2-
deoxy-2-amino carbohydrates to allow a wide range of
functionalized C-glycosides to be obtained. Of particu-
lar note is the efficient metal catalyzed isomerization of
readily available allyl C-glycosides to afford propenyl
C-glycosides a- and b-3 which represent stable interme-
diates that are anticipated to be valuable building
blocks for the preparation of complex, biologically
important oligosaccharides. The application of these
intermediates to the preparation of C-glycopeptides will
be reported in due course.
11. For some additional recent examples, see: (a) Lohof, E.;
Planker, E.; Mang, C.; Burkhart, F.; Dechantsreiter, M.
A.; Haubner, R.; Wester, H.-J.; Schwaiger, M.; Holze-
mann, G.; Goodman, S. L.; Kessler, H. Angew. Chem.,
Int. Ed. 2000, 39, 2761–2764; (b) SanMartin, R.; Tavas-
soli, B.; Walsh, K. E.; Walter, D. S.; Gallagher, T. Org.
Lett. 2000, 2, 4051–4054; (c) Cipolla, L.; La Ferla, B.;
Lay, L.; Peri, F.; Nicotra, F. Tetrahedron: Asymmetry
2000, 11, 295–303; (d) Schafer, A.; Thiem, J. J. Org.
Chem. 2000, 65, 24–29; (e) Pachamuthu, K.; Gupta, A.;
Das, J.; Schmidt, R. R.; Vankar, Y. D. Eur. J. Org.
Chem. 2002, 1479–1483.
12. Cui, J.; Horton, D. Carbohydr. Res. 1998, 309, 319–330.
13. Roe, B. A.; Boojamra, C. G.; Griggs, J. L.; Bertozzi, C.
R. J. Org. Chem. 1996, 61, 6442–6445.
14. Grugier, J.; Xie, J.; Duarte, I.; Balery, J.-M. J. Org.
Chem. 2000, 65, 979–984.
Acknowledgements
15. Muller, S.; Liepold, B.; Roth, G. J.; Bestmann, H. J.
Synlett 1996, 521–522.
16. Bertozzi, C. R.; Bednarski, M. D. Tetrahedron Lett. 1992,
33, 3109–3112.
17. Wong, C.-H.; Varas, F. M.; Hung, S. G.; Marron, T. H.;
Lin, C.-C.; Gong, K. W.; Schmidt, G. W. J. Am. Chem.
Soc. 1993, 119, 8152–8158.
We thank the National Institutes of Health (GM58510)
for support of this work.
References
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3. For reviews see: (a) Postema, M. H. D. C-Glycoside
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21. Only the aldehyde a-4 and a small amount of Ph3P could
1
be detected by H NMR.
22. To our knowledge, this represents the first such epimer-
ization of a 2-deoxy-2-amino sugar. See: Kobertz, W. R.;
Bertozzi, C. R.; Bednarski, M. D. Tetrahedron Lett. 1992,
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26. Even the typically reliable Nozaki reagent led to poor
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27. For
a recent example of ethylene metathesis, see:
Pietraszuk, C.; Marciniec, B.; Jankowska, M. Adv. Synth.
Catal. 2002, 344, 789–793.
28. Selected spectral data: a-2: H NMR (CDCl3) l 1.83 (s,
1
3H), 1.98 (t, J=2.2 Hz, 1H), 2.36 (dd, J=6.8, 2.6 Hz,
2H), 3.58 (t, J=1.3 Hz, 1H), 3.80 (m, 3H), 4.10 (dt,
J=5.2, 1.3 Hz, 1H), 4.46 (m, 6H), 6.53 (d, J=9.8 Hz,
1H), 7.29 (m, 15H); 13C NMR (CDCl3) l 21.7, 23.2, 46.9,
66.9, 67.5, 69.8, 71.7, 72.0, 72.9, 73.3, 74.1, 75.4, 80.4,
127.5, 127.6, 127.7, 127.9, 128.0, 128.3, 128.4, 128.5,
137.2, 138.1, 169.9. b-2: 1H NMR (CDCl3) l 1.80 (s, 3H),
1.97 (t, J=5.4 Hz, 1H), 2.48 (m, 2H), 3.67 (m, 7H), 4.61
7. Wellner, E.; Gustafsson, T.; Backlund, J.; Holmdahl, R.;
Kihlberg, J. Chembiochem 2000, 1, 272–280.

G. J. McGar6ey et al. / Tetrahedron Letters 44 (2003) 3775–3779
3779
(m, 5H), 4.83 (dd, J=17.5, 11.6 Hz, 1H), 5.12 (d, J=7.6
Hz, 1H), 7.27 (m, 15H). 13C NMR (CDCl3) l 22.8, 23.5,
55.3, 68.8, 69.7, 73.4, 74.5, 74.8, 76.7, 78.9, 79.3, 80.8,
82.3, 127.5, 127.81, 127.89, 127.9, 128.1, 128.3, 128.4,
4.83 (dd, J=16.5, 11.9 Hz, 1H), 5.17 (d, J=6.3 Hz, 1H),
7.26 (m, 15H). 13C NMR (CDCl3) l 23.2, 52.5, 53.3, 68.6,
73.4, 74.5, 74.9, 77.5, 78.3, 79.2, 81.4, 127.6, 127.9, 128.0,
128.31, 128.36, 128.44, 128.60, 128.69, 137.9, 138.1, 168.8,
170.2. a-6: 1H NMR (CDCl3) l 1.76 (s, 3H), 2.48 (d,
J=2.4 Hz, 1H), 3.73 (m, 4H), 3.96 (m, 1H), 4.17 (m, 1H),
4.58 (m, 4H), 4.83 (m, 3H), 4.97 (d, J=8.3 Hz, 1H), 7.29
(m, 15H). 13C NMR (CDCl3) l 18.8, 23.3, 48.7, 67.8,
69.4, 72.2, 72.4, 73.2, 73.9, 74.7, 75.1, 126.7, 127.63,
127.67, 127.7, 127.8, 127.9, 128.3, 128.4, 130.0, 137.5,
137.7, 138.1, 169.6. b-6: 1H NMR (CDCl3) l 1.86 (s, 3H),
2.43 (d, J=1.9 Hz, 1H), 3.50 (m, 1H), 3.71 (m, 4H), 3.91
(t, J=9.8 Hz, 1H), 4.39 (dd, J=10.1, 1.7 Hz, 1H), 4.60
(m, 4H), 4.82 (dd, J=17.1, 11.6 Hz, 1H), 5.51 (d, J=8.3
Hz, 1H), 7.24 (m, 15H). 13C NMR (CDCl3) l 23.1, 56.0,
68.2, 68.3, 73.1, 74.0, 74.4, 74.5, 78.1, 78.9, 79.3, 81.2,
127.2, 127.5, 127.7, 128.01, 128.06, 128.1, 137.5, 137.9,
170.0. a-7 (benzyl protected): 1H NMR (CDCl3) l 1.82 (s,
3H), 3.61 (t, J=2.6 Hz, 1H), 3.79 (m, 3H), 4.27 (m, 2H),
4.57 (m, 7H), 5.29 (ddt, J=29.0, 17.3, 1.5 Hz, 1H), 5.77
(ddd, J=17.2, 10.7, 4.8 Hz, 1H), 6.31 (d, J=9.4 Hz, 1H),
7.30 (m, 15H). 13C NMR (CDCl3) l 23.2, 48.2, 67.6, 72.0,
72.1, 72.2, 73.1, 73.2, 73.5, 117.2, 127.6, 127.9, 128.0,
128.1, 128.2, 128.3, 128.4, 132.3, 137.3, 137.5, 138.0,
169.7. a-7 (acetate protected) 1H NMR (CDCl3) l 1.90 (s,
3H), 2.01 (s, 3H), 2.03 (s, 3H), 2.06 (s, 3H), 3.95 (m, 1H),
4.07 (dd, J=3.1, 12.3 Hz, 1H), 4.22 (dd, J=5.4, 11.9 Hz,
1H), 4.33 (m, 1H), 4.62 (t, J=5.8 Hz, 1H), 5.02 (m, 2H),
5.43 (m, 2H), 5.84 (d, J=8.5 Hz, 1H), 5.98 (ddd, J=4.2,
6.2, 10.8, 1H); 13C NMR (CDCl3) l 20.4, 20.5, 20.6, 20.7,
23.0, 51.2, 62.1, 68.4, 70.2, 73.8, 121.9, 130.0, 169.1,
169.8, 170.6, 171.5. b-7: 1H NMR (CDCl3) l 1.78 (s, 3H),
3.50 (m, 1H), 3.74 (m, 6H), 4.60 (m, 4H), 4.84 (dd,
J=15.3, 11.6 Hz, 2H), 5.03 (m, 1H), 5.24 (m, 2H), 5.83
(m, 1H), 7.27 (m, 15H). 13C NMR (CDCl3) l 23.5, 55.0,
68.9, 73.5, 74.4, 74.8, 78.7, 78.9, 80.2, 82.6, 118.7, 127.6,
127.8, 128.0, 128.1, 128.3, 128.4, 128.5, 135.0, 138.0,
138.4, 169.9.
1
128.5, 137.9, 138.2, 138.3, 170.3. a-3 (R=Bn): H NMR
(CDCl3) l 1.18 (d, J=6.3 Hz, 3H), 1.82 (s, 3H), 3.73 (m,
4H), 4.24 (m, 2H), 4.41 (d, J=5.7 Hz, 1H), 4.56 (m, 6H),
5.42 (ddd, J=10.5, 4.8, 1.5 Hz, 1H), 5.76 (m, 1H), 6.19
(d, J=9.2 Hz, 1H), 7.29 (m, 15H). 13C NMR (CDCl3) l
18.0, 23.3, 48.7, 67.8, 69.4, 72.2, 72.4, 73.2, 73.9, 74.7,
75.1, 126.7, 127.63, 127.67, 127.7, 127.8, 127.9, 128.3,
1
128.4, 130.0, 137.5, 137.7, 138.1, 169.6. a-3 (R=Ac): H
NMR (CDCl3) l 1.74 (d, J=6.5 Hz, 3H), 1.87 (s, 3H),
1.99 (s, 3H), 2.03 (s, 3H), 3.87 (m, 1H), 4.02 (dd, J=2.7,
9.0 Hz, 1H), 4.17 (dd, J=5.0, 6.9 Hz, 1H), 4.28 (m, 1H),
4.49 (t, J=6.6 Hz, 1H), 5.01 (m, 2H), 5.74 (m, 3H). 13C
NMR (CDCl3) l 18.2, 20.4, 20.5, 20.6, 23.0, 51.2, 62.2,
68.5, 69.7, 71.0, 74.1, 122.5, 134.9, 169.1, 169.8, 170.6,
171.5. b-3 (R=Bn): 1H NMR (CDCl3) l 1.66 (dd, J=6.3,
1.3 Hz, 3H), 1.78 (s, 3H), 3.48 (m, 1H), 3.67 (m, 6H),
4.61 (m, 4H), 4.82 (dd, J=16.2, 11.3 Hz, 2H), 4.97 (d,
J=6.1 Hz, 1H), 5.47 (dd, J=15.3, 5.7 Hz, 1H), 5.70 (m,
1H), 7.17 (m, 2H), 7.31 (m, 13H). 13C NMR (CDCl3) l
17.8, 23.4, 55.2, 68.9, 73.4, 74.4, 74.8, 78.7, 80.1, 82.8,
127.5, 127.7, 127.8, 127.9, 128.1, 128.3, 128.4, 130.9,
138.03, 138.08, 138.4, 169.7. b-3 (R=Ac): 1H NMR
(CDCl3) l 1.67 (d, J=6.6 Hz, 3H), 1.87 (s, 3H), 1.99 (s,
3H), 2.00 (s, 3H), 2.06 (s, 3H), 3.67 (m, 2H), 4.05 (m,
2H), 4.20 (dd, J=4.6, 12.0 Hz, 1H), 5.05 (m, 2H), 5.46
(dd, J=7.6, 15.4 Hz, 1H), 5.59 (d, J=9.2 Hz, 1H), 5.74
(m, 1H); 13C NMR (CDCl3) l 18.4, 21.0, 21.1, 21.2, 23.7,
54.0, 62.9, 69.0, 74.7, 76.1, 81.3, 123.0, 132.7, 169.8,
170.4, 171.3, 171.9. a-5: 1H NMR (CDCl3) l 1.78 (s, 3H),
3.65 (t, J=8.7 Hz, 1H), 3.74 (m, 6H), 4.14 (m, 1H), 4.58
(m, 8H), 6.40 (d, J=8.7 Hz, 1H), 7.28 (m, 15H). 13C
NMR (CDCl3) l 23.2, 47.9, 52.2, 67.3, 69.9, 72.6, 72.9,
73.2, 74.1, 75.4, 75.6, 127.6, 127.7, 127.94, 127.96, 128.3,
137.8, 169.6, 170.3. b-5: 1H NMR (CDCl3) l 1.76 (s, 3H),
3.54 (m, 1H), 3.73 (m, 7H), 3.96 (m, 2H), 4.61 (m, 4H),