Intramolecular glycosylation approach toward constructing the macrocyclic structure of resin glycosides

Article abstract of DOI:10.1055/s-0029-1218272

Oligosaccharide-containing macrolides of resin glycosides were effectively constructed by MeOTf-promoted intramolecular glycosylation of dodecyl thioglycosyl donors. Synthesis of a key disaccharide intermediate of tricolorin A and total synthesis of trico

Full text of DOI:10.1055/s-0029-1218272

LETTER
2957
Intramolecular Glycosylation Approach toward Constructing the Macrocyclic
Structure of Resin Glycosides
I
ntramolecular
a
G
lycosylat
n
ion
A
pproac
g
h
-Hyun Son,a Natsuko Yanagiya,a Jun-ichi Furukawa,b Nobuo Sakairi*a
a
Graduate School of Environmental Science, Hokkaido University, Kita-ku, Sapporo 060-0810, Japan
Fax +81(11)7062257; E-mail: nsaka@ees.hokudai.ac.jp
b
Graduate School of Advanced Life Science, Hokkaido University, Kita-ku, Sapporo 001-0021, Japan
Received 26 August 2009
ing our recently developed odorless dodecyl
thioglycosides11 as glycosyl donors as depicted in
Scheme 1.
Abstract: Oligosaccharide-containing macrolides of resin glyco-
sides were effectively constructed by MeOTf-promoted intramolec-
ular glycosylation of dodecyl thioglycosyl donors. Synthesis of a
key disaccharide intermediate of tricolorin A and total synthesis of
tricolorin F were successfully achieved by this approach.
The key intermediate (R/S)-5 that has both glycosyl donor
and acceptor functions was prepared by glycosylation and
esterification of racemic methyl 11-jalapionate6a (R/S)-1
with two dodecyl thioglycosides 2 and 4. The first glyco-
sylation was conducted with (R/S)-1 and the quinovoside
(2) using MeOTf12 as a promoter, giving the b-glycoside
(R/S)-3 in 85% yield. After saponification of (R/S)-3, the
resulting acid was esterified with 4 to give (R/S)-5 in 69%
yield.14 The precursor (R/S)-5 was subjected to intramo-
lecular glycosylation under the conditions summarized in
Table 1. Comparison with two promoters, NIS–TfOH13
and MeOTf (entries 2 and 5), showed that the former
reaction gave (R/S)-614 in slightly higher yield with an al-
most same ratio of the diastereomer. Although increasing
the substrate concentration resulted in rapid consumption
of (R/S)-5 and production of various polar products, al-
most same yield (27–35%) of the desired S-isomer (S)-6
was obtained. These results suggest that the R-isomer of
(R/S)-5 easily undergoes intermolecular glycosylation to
afford polymeric compounds. The best results were ob-
tained at the substrate concentration of 2.2 mM with 10
mol equiv promoter, giving (R/S)-6 in 69% yield with a
diastereomeric ratio of R/S = 52:48. For structural eluci-
dation of the products, the corresponding S-isomer (S)-6
was synthesized from (S)-1.
Key words: resin glycoside, macrolide, tricolorin, dodecyl thiogly-
coside, intramolecular glycosylation
Resin glycosides are glycolipids of plant origin are one of
the constituents of the Convolvulaceae (morning glory
family), some of which has been used as traditional folk
medicines.1 Recently, various resin glycosides with
unique biological effects such as antibacterial,2 antifun-
gal,3 cytotoxic,4 and plant-growth controlling activities5
are isolated from leaves and roots of these plants. They are
consisted of several deoxygenated monosaccharides and
hydroxy fatty acids as an aglycon moiety. Most of the bio-
active resin glycosides have unusual macrolidic struc-
tures, in which the aglycon carboxyl group is
intramolecularly esterified with one of the sugar hydroxy
groups. The unique structure and bioactivity attract atten-
tion of synthetic chemists.6 Synthetic studies so far report-
ed on resin glycosides revealed that construction of the
macrolide structure is a crucial step, which was conven-
tionally carried out by intramolecular esterification be-
tween the aglycon carboxylic acid and a sugar hydroxy
group under high-dilution conditions.7 Recently, Fürstner
developed an alternative approach employing ring-
closure metathesis (RCM) for this cyclization, which was
applied to synthesis of various resin glycosides.8 In con-
trast to these two approaches, the oligosaccharide-
containing macrolidic structure would be constructed by
intramolecular glycosylation. In our previous studies on
cycloglycan synthesis, we recognized the usefulness of
thioglycosyl donors for intramolecular glycosylation.9 In
this communication, we describe a model reaction of in-
tramolecular glycosylation and application of this concept
to the syntheses of tricolorin A and F10 having tetra- and
trisaccharide structures, respectively.
Encouraged by these successful results of the model ex-
periments, we next examined the synthesis of a disaccha-
ride constituent of tricolorin A. As shown in Scheme 2,
the D-fucosyl donor 7 was first coupled with enantiomer-
ically pure aglycon7a (S)-1 using MeOTf as a promoter
giving 8 in 81%, which was subsequently saponified and
condensed with the glucosyl donor 11.
Although we chose trichloroethoxycarbonyl (Troc) group
as a temporary protective group of 11, its migration during
the condensation reaction resulted in low isolated yield of
12.14 The key intermediate 12 thus obtained was subjected
to similar MeOTf-promoted intramolecular glycosylation
in CH2Cl2 at a substrate concentration of 2.1 mM, giving
the macrolide14 13 in 67% isolated yield. The coupling
constant (7.6 Hz) between H-1¢ and H-2¢ suggested that
the anomeric configuration of newly formed glycosidic
bond was b.
Applicability of intramolecular glycosylation toward a
model disaccharide (R,S)-6 was first investigated employ-
SYNLETT 2009, No. 18, pp 2957–2960
x
x
.x
x
.2
0
0
9
Advanced online publication: 08.10.2009
DOI: 10.1055/s-0029-1218272; Art ID: U08109ST
© Georg Thieme Verlag Stuttgart · New York

2958
S.-H. Son et al.
LETTER
O
BnO
BnO
C5H11
O
SC12H25
BnO
HO
O
SC12H25
BnO
BnO
O
OBz
OBz
4
2
OBz
a
OH
b
C5H11
CO2Me
(R/S)-1
MeO
O
(R/S)-3
intramolecular glycosylation
C5H11
C5H11
O
O
BnO
BnO
O
BnO
O
O
BnO
c
OH
O
BnO
O
O
BnO
SC12H25
OBz
O
OBz
O
(R/S)-6
O
(R/S)-5
Scheme 1 Intramolecular glycosylation toward a model disaccharide (R/S)-6. Reagents and conditions: (a) MeOTf, MS 4 Å, CH2Cl2, r.t., 1.5
h, 85%; (b) NaOH, THF–EtOH, 50 °C, 7 h; then 4, WSC·HCl, DMAP, CH2Cl2, r.t., 4 h, 69%; (c) MeOTf or NIS–TfOH, MS 4 Å, CH2Cl2;
conditions see Table 1.
Table 1 Results of Intramolecular Glycosylationa
Entry
Promoter (equiv)b
MeOTf (10)
MeOTf (5)
MeOTf (5)
MeOTf (5)
NIS (1.5)
Concentration of 5 (mM) Time (h)
Yield (%)
R/Sc
1
2
3
4
5
2.2
4.5
19
13
13
13
13
69
63
39
35
52
52/48
45/55
29/71
22/78
41/59
8.9
17.8
4.5
a Reactions were performed in dry CH2Cl2 at r.t. for MeOTf and at –20 °C for NIS.
b Catalytic amount of TfOH was added together with NIS.
c Ratio of diastereomers was determined by 1H NMR analysis.
Our attention next focused on the synthesis of a trisaccha- H-1¢¢ and H-2¢¢ were observed as a doublet (J = 10.8 Hz)
ridic resin glycoside, tricolorin F,10 having a 21-mem- and d = 5.01 ppm, respectively, showed that newly formed
bered ring. The D-fucosyl acceptor 9, which was prepared b-D-quinovosyl linkage and the 1,2¢¢-macrolide structure.
by Zemplén de-O-benzoylation of 8, underwent MeOTf- It was noteworthy that H-1 and H-1¢ observed at d = 5.06
promoted glycosylation with the donor 14 to give the dis- and 4.42 ppm as broad doublets probably due to the con-
accharide 15 in 83% yield. In order to transform into the strained structure of its trisaccharide-containing mac-
substrate 19 for intramolecular glycosylation, the ester rolide structure. Finally, global deprotection of 19 was
functions in 15 were hydrolyzed with aqueous NaOH. successfully attained by a two-step procedure involving
Subsequently, the resulting carboxylic acid 16 was to be hydrolysis of the acetal group with 3% HCl–methanol and
coupled with the thioquinovoside 17. Stoichiometric reac- catalytic hydrogenolysis of the O-benzyl groups over Pd/
tion between 16 and 17 gave a complex mixture contain- C in MeOH, giving tricolorin F (20)7a in almost quantita-
ing the desired 19 only in 9% yield probably due to tive yield (Scheme 3).
polymerization. This problem was overcome by use of ex-
In conclusion we have succeeded in synthesis of the mac-
cess alcohol 17 (5 mol equiv) to give 18 in 72% yield. In
rolidic structures of resin glycosides through novel in-
1
its H NMR spectrum, a signal assignable to H-2 of the
tramolecular glycosylation approach. Combination with
quinovose residue was observed at lower magnetic field
macrolactonization and RCM, the new methodology
of d = 4.95 ppm as a triplet (J = 9.6 Hz), suggesting that
would provide various synthetic analogues useful for a
systematic survey of the biological functions of resin gly-
cosides.
the hydroxy group at this position was esterified. The next
intramolecular glycosylation of 18 using similar MeOTf
method found to proceed smoothly in CH2Cl2 at the sub-
strate concentration of 1.8 mM, giving known fully pro-
tected derivative 197a of tricolorin F in 70% yield. Its
structure was confirmed mainly by NMR spectroscopy;14
Synlett 2009, No. 18, 2957–2960 © Thieme Stuttgart · New York

LETTER
Intramolecular Glycosylation Approach
2959
Acknowledgment
O
Me
C5H11
O
We would like to thank Ms A. Maeda and Ms H. Matsumoto at Cen-
ter for Instrumental Analysis, Hokkaido University for measuring
elemental analyses, and Ms S. Oka at the same center for recoding
MS spectra.
O
O
O
O
OR1
H
(S)-1
O
SC12H25
a
OBz
7
R2O
References and Notes
O
(1) Pereda-Miranda, R.; Bah, M. Curr. Top. Med. Chem. 2003,
3, 111.
(2) Cherigo, L.; Pereda-Miranda, R.; Fragoso-Serrano, M.;
Jacobo-Herrera, N.; Kaatz, G. W.; Gibbons, S. J. Nat. Prod.
2008, 71, 1037.
8
9
R
1 = Bz, R2 = Me
R1 = H, R2 = Me
b
c
10 R1, R2 = H
(3) Barnes, C. C.; Smalley, M. K.; Manfredi, K. P.; Kindscher,
K.; Loring, H.; Sheeley, D. M. J. Nat. Prod. 2003, 66, 1457.
(4) Pereda-Miranda, R.; Mata, R.; Anaya, A. L.;
Wickramaratne, D. B. M.; Pezzuto, J. M.; Kinghorn, A. D.
J. Nat. Prod. 1993, 56, 571.
(5) Leon, I.; Enriquez, R. G.; Gnecco, D.; Villarreal, M. L.;
Cortes, D. A.; Reynolds, W. F.; Yu, M. J. Nat. Prod. 2004,
67, 1552.
OBn
O
O
O
BnO
HO
SC12H25
O
O
H
OTroc
11
OBn
OH
C5H11
O
BnO
SC12H25
O
d
OTroc
O
12
(6) (a) Fürstner, A. Eur. J. Org. Chem. 2004, 943.
(b) Furukawa, J.; Sakairi, N. Trends Glycosci. Glycotechnol.
2001, 13, 1.
O
(7) (a) Brito-Arias, M.; Pereda-Miranda, R.; Heathcock, C. H.
J. Org. Chem. 2004, 69, 4567. (b) Zhu, X.-M.; He, L.-L.;
Yang, G.-L.; Lei, M.; Chen, S.-S.; Yang, J.-S. Synlett 2006,
3510; and references cited therein.
(8) (a) Fürstner, A.; Müller, T. J. Org. Chem. 1998, 63, 424.
(b) Fürstner, A.; Müller, T. J. Am. Chem. Soc. 1999, 121,
7814. (c) Fürstner, A.; Jeanjean, F.; Razon, P. Angew. Chem.
Int. Ed. 2002, 41, 2097. (d) Fürstner, A.; Jeanjean, F.;
Razon, P.; Wirtz, C.; Mynott, R. Chem. Eur. J. 2003, 9, 307.
(e) Fürstner, A.; Jeanjean, F.; Razon, P.; Wirtz, C.; Mynott,
R. Chem. Eur. J. 2003, 9, 320.
O
O
O
H
e
OBn
O
C5H11
BnO
O
O
OTroc
O
13
Scheme 2 Synthesis of a disaccharide constituent of tricolorin A
(13). Reagents and conditions: (a) MeOTf, MS 4 Å, CH2Cl2, r.t., 1 h,
81%; (b) NaOMe, MeOH, 40 °C, 10 h, 96%; (c) NaOH, THF–EtOH,
50 °C, 6 h, 78%; (d) WSC·HCl, DMAP, CH2Cl2, r.t., 24 h, 12%; (e)
MeOTf, MS 4 Å, CH2Cl2, r.t., 3 d, 67%.
(9) (a) Sakairi, N.; Wang, L.-X.; Kuzuhara, H. J. Chem. Soc.,
Chem. Commun. 1991, 289. (b) Sakairi, N.; Kuzuhara, H.
J. Chem. Soc., Chem. Commun. 1993, 1874.
O
O
C5H11
BnO
BnO
O
SC12H25
O
O
OBn
O
OH
17
OBn
O
H
9
BnO
BnO
R2O
BnO
BnO
O
SC12H25
c
a
OR1
OBz
14
O
15 R1 = Bz, R2 = Me
16 R1, R2 = H
b
O
OH
HO
O
O
C5H11
O
C5H11
O
O
O
O
C5H11
O
O
OBn
H
OH
OBn
O
H
O
BnO
BnO
H
O
O
HO
HO
O
BnO
BnO
O
d
O
e
OH
BnO
BnO
O
O
O
HO
HO
O
BnO
BnO
SC12H25
O
O
O
O
O
O
18
19
20
Scheme 3 Total synthesis of tricolorin F. Reagents and conditions: (a) MeOTf, MS 4 Å, CH2Cl2, r.t., 6 h, 83%; (b) NaOH, THF–EtOH, 50 °C,
4 h, 99%; (c) WSC·HCl, DMAP, CH2Cl2, r.t., 24 h, 72%; (d) MeOTf, MS 4 Å, CH2Cl2, r.t., 24 h, 70%; (e) i) HCl, MeOH, r.t., 2 h; ii) Pd/C, H2,
MeOH, r.t., 24 h, 99%.
Synlett 2009, No. 18, 2957–2960 © Thieme Stuttgart · New York

2960
S.-H. Son et al.
LETTER
(10) (a) Bah, M.; Pereda-Miranda, R. Tetrahedron 1996, 52,
13063. (b) Bah, M.; Pereda-Miranda, R. Tetrahedron 1997,
42, 9007.
128.2, 128.0, 102.3, 99.5, 86.1, 84.1, 83.2, 82.2, 76.5, 75.8,
75.6, 75.5, 75.1, 71.5, 70.9, 35.3, 35.0, 34.6, 32.5, 31.6, 29.8,
28.4, 28.1, 27.3, 25.7, 25.4, 23.4, 23.1, 18.4, 14.6. HRMS–
FAB: m/z calcd for C56H72O11 [M + Na]+: 943.4995; found:
943.4995.
(11) (a) Hasegawa, J.; Hamada, M.; Miyamoto, T.; Nishide, K.;
Kajimoto, T.; Uenishi, J.; Node, M. Carbohydr. Res. 2005,
340, 2360. (b) Matsui, H.; Furukawa, J.; Awano, T.; Nishi,
N.; Sakairi, N. Chem. Lett. 2000, 326. (c) Son, S.-H.; Tano,
C.; Furukawa, J.; Furuike, T.; Sakairi, N. Org. Biomol.
Chem. 2008, 6, 1441. (d) Son, S.-H.; Tano, C.; Furuike, T.;
Sakairi, N. Tetrahedron Lett. 2008, 49, 5289. (e) Son,
S.-H.; Tano, C.; Furuike, T.; Sakairi, N. Carbohydr. Res.
2009, 344, 285.
Compound 12: [a]D –7.2 (c 0.76, CHCl3). 1H NMR (300
MHz, acetone-d6): d = 7.40–7.25 (m, 10 H, 2 CHarom), 5.40
(t, 1 H, J3¢,4¢ = 8.9 Hz, H-3¢), 4.97–4.57 (m, 6 H, PhCH2,
Cl3CCH2), 4.82 (d, 1 H, J1¢,2¢ = 10.0 Hz, H-1¢), 4.73 (t, 1 H,
J2¢,3¢ = 9.6 Hz, H-2¢), 4.22 (d, 1 H, J1,2 = 8.1 Hz, H-1), 4.03
(dd, 1 H, J = 2.2 Hz, J4,5 = 6.0 Hz, H-4), 4.00–3.96 (m, 1 H,
H-3), 3.91 (dd, 1 H, J = 2.1, 6.5 Hz, H-5), 3.86–3.75 (m, 4
H, H-4¢, H-5¢, H-6¢a, H-6¢b), 3.63–3.60 (m, 1 H, CHO), 3.35
(t, 1 H, J2,3 = 7.6 Hz, H-2), 2.85–2.65 (m, 2 H, SCH2), 2.33–
2.20 (m, 2 H, CH2COO), 1.52–1.28 [m, 53 H, H-6, C(CH3)2,
22 × CH2], 0.91–0.86 (m, 6 H, 2 × CH3). Column
(12) Lönn, H. Carbohydr. Res. 1985, 139, 115.
(13) Mootoo, D. R.; Konradsson, P.; Udodong, U.; Fraser-Reid,
B. J. Am. Chem. Soc. 1988, 110, 5583.
(14) All new compounds had satisfactory data for elemental
analysis or high resolution mass spectrum.
chromatography of the mixture gave crude 12 contaminated
with small amount of an unknown product in ca. 60% yield
and a mixture of 11 its 3-O-Troc derivative. Repeated
column chromatography gave pure 12 in 12% yield.
Compound 13: [a]D +2.1 (c 0.33, CHCl3). 1H NMR (300
MHz, acetone-d6): d = 7.44–7.29 (m, 10 H, CHarom), 5.48 (t,
1 H, J3¢,4¢ = 8.6 Hz, H-3¢), 5.36 (d, 1 H, J1¢,2¢ = 7.6 Hz, H-1¢),
5.08–4.63 (m, 6 H, PhCH2, Cl3CCH2), 4.57 (dd, 1 H, J = 7.6
Hz, J2¢,3¢ = 8.8 Hz, H-2¢), 4.23 (d, 1 H, J1,2 = 8.4 Hz, H-1),
4.11 (dd, 1 H, J = 5.3 Hz, J4,5 = 7.0 Hz, H-4), 4.05 (dd, 1 H,
J = 2.0 Hz, J3,4 = 5.3 Hz, H-3), 3.95–3.84 (m, 5 H, H-2, H-5,
H-4¢, H-6¢a, H-6¢b), 3.71–3.65 (m, 1 H, H-5¢), 3.55–3.49 (m,
1 H, CHO), 2.33–2.00 (m, 2 H, CH2COO), 1.53–1.24 [m, 33
H, H-6, C(CH3)2, 12 × CH2], 0.86 (t, 3 H, J = 6.8 Hz,
CH2CH3). 13C NMR (75.5 MHz, acetone-d6): d = 171.8,
153.4, 139.1, 138.8, 128.6, 128.3, 128.2, 128.0, 127.7,
109.6, 101.5, 97.0, 95.3, 81.2, 80.5, 80.2, 77.0, 76.9, 75.5,
75.1, 74.7, 74.5, 73.5, 68.6, 68.3, 35.4, 35.2, 34.5, 32.1, 31.1,
30.1, 29.9, 29.6, 29.3, 29.1, 28.8, 28.6, 28.3, 28.2, 27.9, 27.4,
26.3, 25.4, 25.1, 24.2, 22.8, 16.7, 13.9. HRMS–FAB: m/z
calcd for C48H67Cl3O13 [M + Na]+: 979.3545; found:
979.3542.
Selected Physical Data
Compound (R,S)-5: 1H NMR (300 MHz, CDCl3): d = 8.02–
7.25 (m, 20 H, CHarom), 5.45 (t, 1 H, J3¢,4¢ = 9.4 Hz, H-3¢),
5.19 (t, 1 H, J2¢,3¢ = 9.8 Hz, H-2¢), 4.97–4.61 (m, 6 H,
PhCH2), 4.57 (d, 1 H, J1¢,2¢ = 10.0 Hz, H-1¢), 4.25 (d, 1 H,
J1,2 = 7.1 Hz, H-1), 3.61–3.48 (m, 4 H, H-2, H-3, H-5¢,
OCH), 3.41–3.33 (m, 2 H, H-5, H-4¢), 3.20 (t, 1 H, J4,5 = 8.6
Hz, H-4), 2.69–2.63 (m, 2 H, SCH2), 2.26 (s, 1 H, OH), 2.09
(t, 2 H, J = 7.3 Hz, CH2COO), 1.57–0.85 (m, 56 H, H-6, H-
6¢, 22 × CH2, 2 × CH3). Although (R)-5 and (S)-5 were not
distinguished by both 1H NMR and 13C NMR spectra, the
diastereomeric ratio of almost 1:1 was deduced by careful
HPTLC (Merck) analysis on silica gel using hexane–EtOAc
(2:1).
Compound (R)-6: [a]D +13.3 (c 1.05, CHCl3). 1H NMR (300
MHz, CDCl3): d = 7.90–7.19 (m, 20 H, CHarom), 5.41 (t, 1 H,
J3¢,4¢ = 8.6 Hz, H-3¢), 5.23 (t, 1 H, J2¢, 3¢ = 7.7 Hz, H-2¢), 5.14
(d, 1 H, J1¢,2¢ = 7.7 Hz, H-1¢), 4.75–4.48 (m, 6 H, PhCH2),
4.39 (d, 1 H, J1,2 = 7.7 Hz, H-1), 3.85–3.76 (m, 2 H, H-2,
OCH), 3.53–3.45 (m, 1 H, H-5¢), 3.42 (t, 1 H, J4¢,5¢ = 9.2 Hz,
H-4¢), 3.41 (t, 1 H, J3,4 = 8.5 Hz, H-3), 3.29–3.22 (m, 1 H, H-
5), 3.11 (t, 1 H, J4,5 = 9.1 Hz, H-4), 2.29–2.08 (m, 2 H,
CH2COO), 1.67–1.21 (m, 30 H, H-6, H-6¢, 12 × CH2), 0.88
(t, 3 H, J = 6.7 Hz, CH2CH3). 13C NMR (75.5 MHz, CDCl3):
d = 172.4, 165.4, 138.5, 138.1, 133.4, 130.2, 130.1, 129.0,
128.8, 128.4, 128.4, 128.2, 128.0, 99.6, 95.6, 86.4, 84.4,
82.9, 81.0, 76.2, 75.8, 75.6, 75.4, 74.9, 71.2, 71.1, 34.9, 34.5,
34.5, 32.6, 31.2, 29.4, 28.3, 28.0, 27.9, 26.9, 23.1, 18.5, 18.4,
14.6. HRMS–FAB: m/z calcd for C56H72O11 [M + Na]+:
943.4995; found: 943.4995.
Compound 19: [a]D –20.5 (c 0.064, CHCl3). 1H NMR (600
MHz, acetone-d6): d = 7.41–7.20 (m, 25 H, CHarom), 5.06 (d,
1 H, J1¢, 2¢ = 7.4 Hz, H-1¢), 5.01 (s, 1 H, H-1¢¢), 5.01 (t, 1 H,
J2¢¢,3¢¢ = 4.5 Hz, H-2¢¢), 5.01–4.61 (m, 10 H, PhCH2), 4.45 (t,
1 H, J3,4 = 6.3 Hz, H-3), 4.42 (d, 1 H, J1,2 = 6.4 Hz, H-1),
4.12 (dd, 1 H, J = 2.0 Hz, J4,5 = 5.7 Hz, H-4), 3.98–3.91 (m,
1 H, H-5), 3.94 (t, 1 H, J2,3 = 6.4 Hz, H-2), 3.80–3.74 (m, 2
H, H-6¢a, 6¢b), 3.69 (t, 1 H, J3¢,4¢ = 7.7 Hz, H-3¢), 3.64 (m, 1
H, H-3¢¢), 3.61 (t, 1 H, J2¢,3¢ = 7.4 Hz, H-2¢), 3.58 (t, 1 H,
Compound (S)-6: [a]D +25.6 (c 0.20, CHCl3). 1H NMR (300
MHz, CDCl3): d = 7.92–7.17 (m, 20 H, CHarom), 5.42 (t, 1 H,
J4¢,5¢ = 7.3 Hz, H-4¢), 3.56 (m, 2 H, H-5¢¢, CHO), 3.46–3.42
(m, 1 H, H-5¢), 3.32 (t, 1 H, J4¢¢, 5¢¢ = 9.1 Hz, H-4¢¢), 2.13 (t, 2
H, J = 7.6 Hz, CH2COO), 1.70–0.85 [m, 39 H, H-6, H-6¢¢,
12 × CH2, C(CH3)2, CH2CH3]. 13C NMR (75.5 MHz,
acetone-d6): d = 172.6, 138.9, 138.7, 138.5, 138.3, 129.0,
128.9, 128.8, 128.6, 128.5, 128.3, 128.2, 128.1, 127.9,
127.6, 110.2, 102.9, 100.8, 83.8, 78.7, 77.7, 75.9, 75.8, 75.6,
75.5, 75.4, 74.0, 72.0, 68.8, 36.6, 35.4, 34.5, 32.5, 30.2, 30.1,
29.4, 28.2, 28.1, 28.0, 26.9, 25.5, 23.1, 18.7, 17.3, 14.6.
HRMS–FAB: m/z calcd for C72H96O15 [M + H]+: 1199.6672;
found: 1199.6640.
J3¢,4¢ = 8.6 Hz, H-3¢), 5.23 (t, 1 H, J2¢,3¢ = 8.3 Hz, H-2¢), 5.07
(d, 1 H, J1¢,2¢ = 7.6 Hz, H-1¢), 4.75–4.46 (m, 6 H, PhCH2),
4.24 (d, 1 H, J1,2 = 7.8 Hz, H-1), 3.82 (dd, 1 H, J = 8.0 Hz,
J2,3 = 9.3 Hz, H-2), 3.53–3.46 (m, 2 H, H-5¢, OCH), 3.40 (t,
1 H, J4¢,5¢ = 9.2 Hz, H-4¢), 3.40 (t, 1 H, J3,4 = 8.4 Hz, H-3),
3.31–3.26 (m, 1 H, H-5), 3.11 (t, 1 H, J4,5 = 9.2 Hz, H-4),
2.19 (s, 2 H, CH2COO), 1.59–1.22 (m, 30 H, H-6, H-6¢,
12 × CH2), 0.89 (t, 3 H, J1,2 = 6.4 Hz, CH2CH3). 13C NMR
(75.5 MHz, CDCl3): d = 172.4, 165.5, 138.5, 138.2, 133.4,
130.2, 130.1, 129.0, 128.9, 128.8, 128.4, 128.3, 128.3,
Synlett 2009, No. 18, 2957–2960 © Thieme Stuttgart · New York

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