Chain elongation of monosaccharides by sequential cross metathesis and asymmetric dihydroxylation: Expeditious approach to higher sugars

Article abstract of DOI:10.1016/j.tetlet.2011.10.024

Glucose-derived alkenes were homologated via chain elongation to afford higher sugars by the application of cross metathesis with an alkene followed by Sharpless asymmetric dihydroxylation. Heptose, octose, nonose, and decose derivatives were expeditiousl

Full text of DOI:10.1016/j.tetlet.2011.10.024

Tetrahedron Letters 52 (2011) 6767–6771
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Chain elongation of monosaccharides by sequential cross metathesis and
asymmetric dihydroxylation: expeditious approach to higher sugars
⇑
⇑
Prithwish Kumar Jana, Sukhendu B. Mandal , Anup Bhattacharjya
Chemistry Division, Indian Institute of Chemical Biology (A Unit of CSIR), 4, Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Glucose-derived alkenes were homologated via chain elongation to afford higher sugars by the applica-
tion of cross metathesis with an alkene followed by Sharpless asymmetric dihydroxylation. Heptose,
octose, nonose, and decose derivatives were expeditiously prepared by this method.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 30 July 2011
Revised 4 October 2011
Accepted 6 October 2011
Available online 15 October 2011
Keywords:
Monosaccharide
Chain elongation
Cross metathesis
Asymmetric dihydroxylation
Higher sugars
Heptose
Octose
Nonose
Decose
Carbohydrates play a vital role in living systems. Their profound
biological importance has made the synthesis of carbohydrates and
their derivatives an important task for synthetic chemists.
Although the majority of carbohydrate derivatives are made up
of hexose and pentose units, significant effort has been noticed
in the area of synthesis of higher sugars because of the biological
activity found in some natural products containing sugar units,
which have a higher number of carbon atoms than pentoses and
hexoses.1–4 In this context it is imperative that an efficient method
for homologation of readily available pentoses or hexoses will en-
able the synthesis of higher monosaccharides, which will be useful
for future research in the area of carbohydrates. The classical Kili-
ani synthesis has served its purpose, but the use of cyanide makes
its application rather restricted. There have been reports of other
homologation procedures, which are efficient but require reagents
that may not be user friendly.
allylic stannanes followed by substrate-directed hydroxylation.6,7
Synthesis of higher dialdoses has been achieved by using suitable
thiazole-bearing reagents.8 2-(Trimethylsilyl)thiazole8–10 and allyl-
oxymethylmagnesium chloride11 have been employed for one-car-
bon homologation. An attractive approach to the homologation
process would be the use of a methodology in which the homolo-
gating partner has a flexible length, so that the same method would
furnish higher sugars of varying sizes. We outline in Scheme 1 an
expeditious strategy, which could be utilized to homologate an
alkenic sugar derivative 1 to a higher sugar 4 via chain elongation
by employing two well-known and remarkably efficacious reac-
tions used in organic synthesis. One of these reactions is cross
metathesis, which has been fruitfully used for the coupling of two
alkene fragments.12,13 We envisaged that the application of cross
metathesis reaction between two alkene counterparts, one of which
is a monosaccharide template 1 and the other is alkene 2 with vary-
ing number of carbon atoms and hydroxyl groups, would lead to
alkene 3 (Scheme 1). The molecule 3 is a dehydro sugar, and intro-
duction of two hydroxyl groups would transform 3 to its native
form 4. Sharpless asymmetric dihydroxylation procedure has been
widely employed to introduce hydroxyl groups on alkenes
stereoselectively,14,15 and application of this reaction to 3 would
serve the desired purpose, and make available a higher sugar
derivative 4. The homologation in this case is achieved via the
extension of the tail-end of the monosaccharide unit, and the extent
As examples, Casiraghi reported four-carbon homologation of
aldehydo-sugars by using 2-(trimethylsi1oxy)furan.5 In another ap-
proach, two- to three-carbon homologation was demonstrated by
Marshall by stereoselective synthesis of higher sugars by the reac-
tion of carbohydrate-derived enals with nonracemic
c-(silyloxy)
⇑
Corresponding authors. Tel.: +91 33 24995758; fax: +91 33 24735197 (A.B.).
E-mail addresses: anupbh@hotmail.com, anupbhattacharjya@iicb.res.in
(A. Bhattacharjya).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.10.024

6768
P. K. Jana et al. / Tetrahedron Letters 52 (2011) 6767–6771
Alkene 5 obtained from D-glucose according to known proto-
(CHOH)n
OR
HOH2C
O
col16 was subjected to cross metathesis with allyl alcohol in the
presence of Grubbs second generation catalyst and Triton X-100
in water following a recently developed procedure (Scheme 2).17
The product obtained in 62% yield was identified to be E-alkene
6 as evident from the vicinal J value of 15.9 Hz for one of the alkene
protons in the 1H NMR spectrum taken in C6D6. The cross metath-
esis could also be achieved by using non-aqueous medium,
although the yields were poorer. The next step involved the intro-
duction of hydroxyl groups on the alkene moiety, which was
accomplished by employing the efficient and operationally simple
Sharpless asymmetric dihydroxylation procedure. As a random
choice the chiral ligand (DHQ)2PHAL was used for this purpose.14,15
Dihydroxylation of 6 using K2OsO4 as the osmium source and the
aforementioned ligand resulted in the formation of diol 7 in 87%
yield as a 4.5:1 diastereomeric mixture as evident from its 1H
NMR spectrum (Scheme 2). The individual components of the mix-
ture could not be separated, and instead, the mixture was acety-
lated for characterization to give again an inseparable 4.5:1
diastereomeric mixture of heptose acetate 8. The introduction of
two hydroxyl groups in the hydroxylation reaction was evident
from the mass spectrum as well as the 1H NMR spectrum of 8
exhibiting singlets due the corresponding acetates.
2
cross metathesis
1
monosaccharide
derived alkene
(CHOH)n
OR
O
HOH2C
OH
3
(CHOH)n
dihydroxylation
OR
O
HOH2C
OH
4
homologated monosaccharide
The known enantiomerically pure alkene 1018,19 was used as
the cross metathesis partner in order to achieve two-carbon chain
elongation according to Scheme 3. Reaction between 10 and alkene
5 using Grubbs second generation catalyst in refluxing benzene led
to E-alkene 11 in 64% yield. Unlike the previously mentioned cross
metathesis reaction the use of aqueous medium containing Triton
X-100 gave poorer yields in this and the reactions described later.
Dihydroxylation of 11 gave a single carbohydrate derivative 12.
Scheme 1. Chain elongation of monosaccharide by cross metathesis and asym-
metric dihydroxylation.
of homologation is determined by the value of n. We demonstrate
herein the application of this strategy by the synthesis of seven-
to ten-membered protected monosaccharide derivatives from al-
kene 5.
HO
allyl alcohol,
O
O
O
O
7.4 mol % G2,
Triton X 100, H2O, 25 oC,
48 h, 62%
O
O
BnO
BnO
5
6
(DHQ)2PHAL (10 mol %),
K2CO3, K3Fe(CN)6,
K2OsO4. 2H2O (3 mol %),
t-BuOH:H2O (1:1), 0 oC,
19 h, 87%
AcO
AcO
HO
HO
OAc
O
OH
O
Ac2O, Py,
O
O
H
H
DMAP, 0-25 oC ,
O
O
BnO
BnO
14 h, 87%
7
8
4.5:1 mixture
of diastereomers
4.5:1 mixture
of diastereomers
N
N
Cl
Ru
Cl
Cy3P
Grubbs second
generation catalyst (G2)
Ph
Scheme 2. Homologation of hexose 5 to heptose 8.

P. K. Jana et al. / Tetrahedron Letters 52 (2011) 6767–6771
6769
OAc
BnO
5, G2 (3.6 mol
AcO
%), benzene,
O
OAc
OH
ref. 9
reflux, 16 h, 64%
O
AcO
HO
O
9
10
11
OAc
OAc
Ac2O, Py,
OAc
O
OH
O
DMAP, 0 -25 oC, AcO
16 h, 75%
(DHQ)2PHAL (10 mol %),
K2CO3, K3Fe(CN)6,
AcO
AcO
O
HO
O
H
H
K2OsO4. 2H2O (4 mol %),
t-BuOH:H2O (1:1),
0 oC, 19 h, 85%
O
O
BnO
BnO
13
12
Scheme 3. Homologation of hexose 5 to octose 13.
The mass spectrum of 12 was consistent with the introduction of
two hydroxyl groups. The assignment of stereochemistry to the
newly formed diol in 12 proved problematic due to the overlapping
nature of the 1H NMR signals of the relevant protons. The direct
assignment of stereochemistry by X-ray crystallographic method
was also precluded by our inability to obtain solid derivatives of
the diols suitable for this purpose. This is why we had to take re-
course to the mnemonic device formulated by Sharpless for pre-
dicting the stereochemistry of the diol formed in the
dihydroxylation reaction using DHQ,14,15 and the indicated stereo-
chemistry of 12 was tentatively assigned on the basis of this rule.20
Diol 12 was characterized as acetate 13, which represents a pro-
tected octose.
partners required for cross metathesis. For the purpose of three-
carbon chain elongation of 5, alkene 14 was prepared from 5 as
shown in Scheme 4. Following a known methodology,21 5 was
deprotected with aq H2SO4, followed by cleavage with NaIO4 giving
an aldehyde, and subsequent NaBH4 reduction and acetylation led
to the formation of alkene 14 in 46% overall yield. Cross metathesis
between 5 and 14 in the presence of Grubbs second generation cat-
alyst in refluxing benzene gave rise to E-alkene 15 in 62% yield.
Dihydroxylation of 15 led to the formation of the protected nonose
16, which was characterized as the corresponding acetate 17.
Four-carbon chain elongation of 5 required the conversion of 5
to the enantiomerically pure triol 18 as outlined in Scheme 5.
Deprotection of 5 with aq H2SO4 followed by NaBH4 reduction
and subsequent acetylation afforded alkene triacetate 19 in 55%
overall yield. Cross metathesis between 5 and 19 in the presence
of Grubbs second generation catalyst gave rise to E-alkene 20 in
In this work alkene 5 was used as the carbohydrate derivative
undergoing homologation. The same alkene was also advanta-
geously used as a convenient source for some of the other alkene
(i) 4% aq H2SO4-CH3CN,
25 oC, 48 h
(ii) aq. NaIO4, MeOH,
OBn
OAc
0 oC, 2 h
5
(iii) NaBH4, MeOH, 0-25 oC,
12 h
(iv) Py, Ac2O, DMAP, 0-25 oC,
12 h, 46% overall from 5
OAc
5, G2 (3.5 mol %),
14
benzene, reflux,
37 h, 62%
AcO
BnO
OAc
AcO
BnO
OAc
H
(DHQ)2PHAL (10 mol %),
K2CO3, K3Fe(CN)6,
K2OsO4. 2H2O (4 mol %),
t-BuOH:H2O (1:1),
OH
O
O
O
HO
O
H
O
BnO
O
BnO
15
16
0 oC, 22 h, 76%
AcO
BnO
OAc
H
OAc
O
Ac2O, Py,
DMAP, 0-25 oC,
19 h, 85%
AcO
O
O
BnO
17
Scheme 4. Homologation of hexose 5 to nonose 17.

6770
P. K. Jana et al. / Tetrahedron Letters 52 (2011) 6767–6771
Ac2O, Py, DMAP,
0-25 oC, 18 h, 91%
OBn
(i) 4% aq H2SO4-CH3CN,
OBn
25 oC, 48 h
OAc
5
OH
OAc OAc
(ii) NaBH4, THF-H2O (4:1),
0-25 oC, 4 h, 58% overall
from 5
OH OH
19
18
AcO
OAc
(DHQ)2PHAL (10 mol%),
K2CO3, K3Fe(CN)6
K2OsO4. 2H2O (4 mol%),
t-BuOH:H2O (1:1),
OAc
5, G2 (7.0 mol%),
benzene, reflux, 48 h, 51%
BnO
O
O
H
0 oC, 27 h, 73%
O
BnO
20
AcO
OAc
AcO
AcO
OAc
HO
OAc
H
Ac2O, Py, DMAP,
0-25 oC, 25 h, 80%
OAc
H
OAc
O
OH
O
BnO
BnO
O
O
O
O
BnO
BnO
21
22
Scheme 5. Homologation of hexose 5 to decose 22.
51% yield. Dihydroxylation of 20 gave a single carbohydrate deriv-
ative 21 in 73% yield. Acetylation of 21 gave rise to 22, which is a
protected form of a decose.
the sizes of the two alkene partners will enable the synthesis of
carbohydrate molecules including oligosaccharides of any desired
length. Work in this direction will be reported in due course. We
believe that the approach described in this work will be potentially
useful as a general method for synthesizing a variety of carbohy-
drate derivatives.
Monosaccharides higher than pentoses occur predominantly in
the pyranose form. The homologated monosaccharide molecules
described above were synthesized as protected furanosides. In or-
der to demonstrate their conversion to the corresponding pyrano-
sides, the C10 carbohydrate derivative 22 was subjected to removal
of 1,2-isopropylidene group by treatment with aq H2SO4, during
which acetates were also hydrolyzed. The resulting mixture was
acetylated to furnish the pyranose derivative 23 as a 1:1 insepara-
ble anomeric mixture of acetates (Scheme 6). The structure of 23
was secured by NMR and high resolution mass spectroscopic tech-
niques. The occurrence of two single proton doublets at d 6.32
(J = 3.6 Hz) and d 5.54 (J = 8.4 Hz) in the 1H NMR spectrum as well
Acknowledgments
PKJ thanks the CSIR for Senior Research Fellowship. SBM thanks
the CSIR for financial support from Network Project (No.
NWP0036). AB gratefully acknowledges the award of Emeritus
Scientist Fellowship by the CSIR, India. Thanks are due to Mr. K.
Sarkar for HRMS measurements.
as peaks at 89.4 and 91.9 in the 13C NMR spectrum due to the
a-
Supplementary data
and b-anomeric protons and carbon atoms was consistent with
the pyranose structure.22
Supplementary data (1H and 13C NMR spectra of 6, 8, 11,13, 15,
17, 20, 22 and 23) associated with this article can be found, in the
online version, at doi:10.1016/j.tetlet.2011.10.024.
In conclusion, the above work revealed an expeditious strategy
for versatile homologation of monosaccharides. The scope of the
methodology can be appreciated from the fact that the method
employs two efficient reactions viz. alkene cross metathesis and
dihydroxylation of an alkene. Both reactions are general, and in
principle, elongation can be effected from any site containing an al-
kene residue, not necessarily the tail-end. Moreover, variation in
References and notes
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D. A.; Grubbs, R. H. J. Am. Chem. Soc. 2000, 122, 58–71.
13. Chatterjee, A. K.; Choi, T.-L.; Sanders, D. P.; Grubbs, R. H. J. Am. Chem. Soc. 2003,
125, 11360–11370.
OAc
OAc
(i) H2SO4 -CH3CN -H2O
OAc
AcO
(1:18:6), 25 oC, 17 h, 90%
(ii) Py, Ac2O, DMAP, 0 -25 oC,
26 h, 74% overall from 22
O
BnO
22
OAc
OBn
H
AcO
AcO
23
14. Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94, 2483–
2547.
Scheme 6. Conversion of decofuranose 22 to decopyranose 23.

P. K. Jana et al. / Tetrahedron Letters 52 (2011) 6767–6771
6771
15. Kolb, H. C.; Andersson, P. G.; Sharpless, K. B. J. Am. Chem. Soc. 1994, 116, 1278–
1291.
16. Rathbone, E. B.; Woolard, G. R. Carbohydr. Res. 1976, 48, 143–146.
17. Lipshutz, B. H.; Aguinaldo, G. T.; Ghorai, S.; Voigtritter, K. Org. Lett. 2008, 10,
1325–1328.
18. Kulkarni, S. S.; Gervay-Hague, J. Org. Lett. 2006, 8, 5765–5768.
19. Alkene 10 was prepared from diol (S)-9 (Aldrich catalog no. 19159) by
acetylation with acetic anhydride and pyridine.
7.26–7.29 (m, 4H): 13C NMR (150 MHz, CDCl3): d 20.8 (CH3), 20.9 (CH3), 26.2
(CH3), 26.8 (CH3), 63.2 (CH2), 72.0 (CH2), 72.3 (CH), 73.0 (CH2), 77.5 (CH), 80.3
(CH), 82.9 (CH), 83.3 (CH), 104.8 (CH), 111.6 (C), 127.5 (2 ꢂ CH), 127.81 (CH),
127.84 (CH), 128.0 (2 ꢂ CH), 128.2 (CH), 128.3 (CH), 128.36 (2 ꢂ CH), 128.4
(2 ꢂ CH), 137.5 (C), 137.8 (C), 169.8 (C), 170.7 (C); HRMS (ESI, positive ion)
Calcd for C30H36O9Na, m/z 563.2257. Found, 563.2227. Compound 17: colorless
viscous liquid, ½a D25
ꢁ15.7 (c 0.21, CHCl3); IR (neat): 1748, 1372, 1220, 1076,
ꢀ
1035, 748 cmꢁ1 1H NMR (600 MHz, CDCl3): d 1.29 (s, 3H), 1.45 (s, 3H), 2.00 (s,
;
20. In order to apply the mnemonic, the disubstituted alkene was positioned
according to the manner specified in the mnemonic device, and the
(DHQ)2PHAL-osmium reagent was made to approach the alkene from the
bottom face. The indicated stereochemistry of 12, 18, and 21 were all assigned
in this manner.
3H), 2.01 (s, 3H), 2.02 (s, 3H), 2.06 (s, 3H), 3.81 (dd, 1H, J = 4.2, 9.6 Hz), 3.83 (d,
1H, J = 3.0 Hz), 4.13–4.16 (m, 2H), 4.19 (dd, 1H, J = 4.8, 11.4 Hz), 4.47 (d, 1H,
J = 11.4 Hz), 4.53 (d, 1H, J = 12.0 Hz), 4.55 (d, 1H, J = 4.2 Hz), 4.59 (d, 1H,
J = 11.4 Hz), 4.63 (d, 1H, J = 11.4 Hz), 5.22 (dd, 1H, J = 4.2, 8.4 Hz), 5.60 (dd, 1H,
J = 1.8, 7.8 Hz), 5.67 (dd, 1H, J = 1.8, 7.8 Hz), 5.84 (d, 1H, J = 3.6 Hz), 7.25–7.36
(m, 10H); 13C NMR (150 MHz, CDCl3): d 20.77 (2 ꢂ CH3), 20.87 (CH3), 20.94
(CH3), 26.2 (CH3), 26.7 (CH3), 63.4 (CH2), 67.4 (CH), 69.4 (CH), 69.6 (CH), 72.1
(CH2), 73.2 (CH2), 75.2 (CH), 78.2 (CH), 80.9 (CH), 81.3 (CH), 104.9 (CH), 111.7
(C), 127.6 (CH), 128.0 (3 ꢂ CH), 128.2 (2 ꢂ CH), 128.3 (2 ꢂ CH), 128.4 (2 ꢂ CH),
137.0 (C), 138.0 (C), 169.39 (C), 169.42 (C), 170.1 (C), 170.7 (C); HRMS (ESI,
positive ion) Calcd for C34H42O13Na m/z 681.2523. Found, 681.2534. Compound
21. Sengupta, J.; Mukhopadhyay, R.; Bhattacharjya, A.; Bhadbhade, M. M.;
Bhosekar, G. V. J. Org. Chem. 2005, 70, 8579–8582.
22. Spectral data 6: colorless viscous liquid, ½a D25
ꢀ
ꢁ43.2 (c 0.18, CHCl3); IR (neat):
3440, 1688, 1455, 1377, 1215, 1163, 1078, 1020, 739, 699 cmꢁ1
;
1H NMR
(300 MHz, C6D6): d 1.24 (s, 3H), 1.57 (s, 3H), 3.86 (d, 1H, J = 1.8 Hz), 3.91 (d, 2H,
J = 4.2 Hz), 4.30 (d, 1H, J = 12.0 Hz), 4.42 (d, 1H, J = 12.0 Hz), 4.52 (d, 1H,
J = 3.3 Hz), 4.86 (br d, 1H, J = 5.1 Hz), 5.87 (td, 1H, J = 4.2, 15.9 Hz), 6.06–6.16
(m, 2H), 7.18–7.34 (m, 5H); 13C NMR (75 MHz, CDCl3): d 26.2 (CH3), 26.7 (CH3),
62.8 (CH2), 72.1 (CH2), 80.6 (CH), 82.9 (CH), 83.3 (CH), 104.7 (CH), 111.6 (C),
124.8 (CH), 127.7 (2 ꢂ CH), 127.9 (CH), 128.4 (2 ꢂ CH), 134.3 (CH), 137.4 (C);
20: reddish brown viscous material, ½a D25
ꢀ
ꢁ14.9 (c 0.16, CHCl3); IR (neat): 1744,
1454, 1373, 1226, 1077, 741, 699 cmꢁ1
;
1H NMR (600 MHz, C6D6): d 1.11 (s,
3H), 1.41 (s, 3H), 1.59 (s, 3H), 1.63 (s, 3H), 1.73 (s, 3H), 3.69 (dd, 1H, J = 4.2,
5.4 Hz), 3.75 (d, 1H, J = 3.0 Hz), 4.21 (dd, 1H, J = 6.6, 11.4 Hz), 4.27 (d, 1H,
J = 12.0 Hz), 4.31 (d, 1H, J = 12.0 Hz), 4.36 (d, 1H, J = 4.2 Hz), 4.42–4.45 (m, 2H),
4.55 (d, 1H, J = 12.0 Hz), 4.76 (dd, 1H, J = 3.0, 6.6 Hz), 5.57 (m, 1H), 5.83 (t, 1H,
J = 6.0 Hz), 5.88 (d, 1H, J = 4.2 Hz), 6.03 (dd, 1H, J = 6.0, 15.6 Hz), 6.12 (dd, 1H,
J = 6.6, 15.6 Hz), 7.05 (t, 1H, J = 7.2 Hz), 7.10 (t, 1H, J = 7.2 Hz), 7.13 (t, 2H,
J = 7.8 Hz), 7.23 (t, 2H, J = 7.8 Hz), 7.27 (m, 4H); 13C NMR: d 20.6 (CH3), 20.8
(2 ꢂ CH3), 26.1 (CH3), 26.7 (CH3), 62.2 (CH2), 70.0 (CH), 71.9 (CH2), 72.2 (CH),
74.4 (CH2), 77.6 (CH), 80.2 (CH), 82.8 (CH), 83.2 (CH), 104.8 (CH), 111.6 (C),
127.3, 127.7, 127.9, 128.0, 128.1, 128.3 and 128.4 (12 ꢂ CH), 137.3 (C), 137.5
(C), 169.6 (C), 170.0 (C), 170.3 (C); HRMS (ESI, positive ion) Calcd for
HRMS (ESI, positive ion) Calcd for
C
17H22O5Na, m/z 329.1365. Found
329.1347.Compound 8: colorless oil, ½a D25
ꢀ ꢁ47.9 (c 0.22, CHCl3); IR (neat):
1748, 1373, 1218, 1103, 1076, 1028 cmꢁ1 1H NMR (300 MHz, CDCl3; 4.5:1
;
diastereomeric mixture; only peaks due to the major isomer are shown): d 1.31
(s, 3H), 1.46 (s, 3H), 1.96 (s, 3H), 2.02 (s, 3H), 2.07 (s, 3H), 3.88 (d, 1H,
J = 2.7 Hz), 4.01 (dd, 1H, J = 6.9, 11.7 Hz), 4.25 (dd, 1H, J = 3.0, 8.7 Hz), 4.33 (dd,
1H, J = 5.1, 11.7 Hz), 4.44 (d, 1H, J = 11.7 Hz), 4.56–4.60 (m, 2H), 5.42 (m, 1H),
5.49 (dd, 1H, J = 3.0, 9.0 Hz), 5.87 (d, 1H, J = 3.6 Hz), 7.30–7.35 (m, 5H); 13C
NMR (75 MHz, CDCl3): d 20.5 (CH3), 20.60 (CH3), 20.64 (CH3), 26.3 (CH3), 26.7
(CH3), 62.3 (CH2), 67.8 (CH), 70.1 (CH), 71.9 (CH2), 77.6 (CH), 80.4 (CH), 81.3
(CH), 105.0 (CH), 111.8 (C), 128.1 (CH), 128.3 (2 ꢂ CH), 128.4 (2 ꢂ CH), 136.7
(C), 169.1 (C), 169.6 (C), 170.5 (C); HRMS (ESI, positive ion) Calcd for
C
33H40O11Na m/z 635.2468. Found, 635.2457. Compound 22: yellow viscous
material, ½a 2D5
ꢀ
ꢁ30.2 (c 0.52, CHCl3); IR (neat): 1747, 1641, 1372, 1222, 1076,
1040, 756 cmꢁ1
;
1H NMR (600 MHz, CDCl3): d 1.30 (s, 3H), 1.45 (s, 3H), 1.97 (s,
C
23H30O10Na, m/z 489.1737. Found 489.1718. Compound 11: sticky liquid,
ꢁ11.7 (c 0.24, CHCl3); IR (neat): 1735, 1380, 1227, 1163, 1081, 1028, 976,
880 cmꢁ1 1H NMR (300 MHz, C6D6): d 1.23 (s, 3H), 1.54 (s, 3H), 1.72 (s, 3H),
3H), 1.98 (s, 3H), 1.99 (s, 3H), 2.00 (s, 3H), 2.06 (s, 3H), 3.84 (d, 1H, J = 3.0 Hz),
4.00 (dd, 1H, J = 4.8, 6.6 Hz), 4.17 (dd, 1H, J = 7.2, 12.0 Hz), 4.19 (dd, 1H, J = 3.0,
8.4 Hz), 4.33 (dd, 1H, J = 4.2, 12.0 Hz), 4.45 (d, 1H, J = 11.4 Hz), 4.53 (d, 1H,
J = 11.4 Hz), 4.56 (d, 1H, J = 3.6 Hz), 4.62 (d, 1H, J = 12.0 Hz), 4.71 (d, 1H,
J = 11.4 Hz), 5.22 (dt, 1H, J = 4.8, 6.6 Hz), 5.32 (t, 1H, J = 6.0 Hz), 5.52 (dd, 1H,
J = 1.8, 6.0 Hz), 5.58 (dd, 1H, J = 1.8, 8.4 Hz), 5.83 (d, 1H, J = 3.6 Hz), 7.29–7.35
(m, 10H); 13C NMR (150 MHz, CDCl3) d 20.6 (CH3), 20.68 (CH3), 20.74 (CH3),
20.9 (CH3), 21.0 (CH3), 26.3 (CH3), 26.7 (CH3), 62.0 (CH2), 67.1 (CH), 69.9 (CH),
70.36 (CH), 70.41 (CH), 72.1 (CH2), 74.5 (CH2), 75.2 (CH), 77.8 (CH), 80.5 (CH),
81.3 (CH), 104.9 (CH), 111.8 (C), 127.6, 127.8, 128.1, 128.3 and 128.5 (10 ꢂ CH),
136.8 (C), 137.9 (C), 169.3 (C), 169.7 (C), 169.9 (C), 170.3 (C), 170.4 (C); HRMS
(ESI, positive ion) m/z Calcd for C37H46O15Na, 753.2734; found, 753.2709.
½ ꢀ
a 2D5
;
1.75 (s, 3H), 3.80 (d, 1H, J = 3.0 Hz), 4.04 (dd, 1H, J = 6.9, 11.7 Hz), 4.29 (two
doublets merged, 2 ꢂ 1H, J = 12.0 Hz), 4.40 (d, 1H, J = 12.0 Hz), 4.47 (d, 1H,
J = 3.6 Hz), 4.77 (dd, 1H, J = 3.0, 6.6 Hz), 5.72–5.82 (m, 2H), 6.01 (d, 1H,
J = 3.6 Hz), 6.16 (dd, 1H, J = 6.6, 14.4 Hz), 7.20–7.37 (m, 5H, merged with
solvent); 13C NMR (75 MHz, CDCl3): d 20.7 (CH3), 21.0 (CH3), 26.2 (CH3), 26.7
(CH3), 64.8 (CH2), 71.2 (CH), 72.1 (CH2), 80.1 (CH), 82.8 (CH), 82.9 (CH), 104.8
(CH), 111.6 (C), 127.6 (2 ꢂ CH), 127.9 (CH), 128.2 (CH), 128.4 (2 ꢂ CH), 128.9
(CH), 137.3 (C), 169.9 (C), 170.6 (C); HRMS (ESI, positive ion) Calcd for
C
22H28O8Na m/z 443.1682. Found 443.1634. Compound 13: colorless oil, ½a D25
ꢀ
ꢁ44.5 (c 0.32, CHCl3); IR (neat): 1750, 1373, 1218, 1075, 858 cmꢁ1
;
1H NMR
Compound 23: colorless oil, ½a D25
ꢀ
+2.7 (c 0.7, CHCl3); IR (neat): 1749, 1457,
(600 MHz, CDCl3) d 1.30 (s, 3H), 1.47 (s, 3H), 2.00 (s, 6H), 2.02 (s, 3H), 2.08 (s,
3H), 3.87 (d, 1H, J = 3.0 Hz), 4.09 (dd, 1H, J = 6.0, 12.0 Hz), 4.20 (dd, 1H, J = 3.6,
8.4 Hz), 4.35 (dd, 1H, J = 4.2, 12.0 Hz), 4.46 (d, 1H, J = 11.4 Hz), 4.56 (d, 1H,
J = 3.6 Hz), 4.57 (d, 1H, J = 12.0 Hz), 5.26–5.28 (m, 1H), 5.47 (dd, 1H, J = 3.0,
8.4 Hz), 5.50 (dd, 1H, J = 3.0, 6.6 Hz), 5.86 (d, 1H, J = 3.6 Hz), 7.29–7.36 (m, 5H);
13C NMR (150 MHz, CDCl3): d 20.5 (CH3), 20.70 (CH3), 20.74 (CH3), 20.8 (CH3),
26.3 (CH3), 26.8 (CH3), 62.1 (CH2), 67.6 (CH), 69.8 (CH), 69.9 (CH), 72.0 (CH2),
78.3 (CH), 80.8 (CH), 81.3 (CH), 105.0 (CH), 111.9 (C), 128.1 (CH), 128.4
(2 ꢂ CH), 128.5 (2 ꢂ CH), 136.8 (C), 169.37 (C), 169.44 (C), 170.0 (C), 170.6 (C);
HRMS (ESI, positive ion) Calcd for C26H34O12Na m/z 561.1948. Found 561.1943.
1371, 1221, 1044, 749 cmꢁ1
;
1H NMR (600 MHz, CDCl3, 1:1 mixture of
anomers): d 1.91 (s, 3H), 1.93 (s, 3H), 1.97 (s, 3H), 1.98 (s, 3H), 1.99 (s, 3H),
2.00 (s, 3H), 2.02 (s, 3H), 2.03 (s, 3H), 2.05 (s, 3H), 2.08 (s, 3H), 2.09 (s, 3H), 2.10
(s, 3H), 2.11 (s, 3H), 2.13 (s, 3H), 3.71 (t, 1H, J = 9.0 Hz), 3.78 (dd, 1H, J = 2.4,
7.2 Hz), 3.80 (dd, 1H, J = 1.8, 10.2 Hz), 3.83 (br d, 1H, J = 6.0 Hz), 3.89 (t, 1H,
J = 9.6 Hz), 3.99 (dd, 1H, J = 6.6, 12.0 Hz), 4.08 (dd, 1H, J = 6.0, 12.6 Hz), 4.15 (d,
1H, J = 10.2 Hz), 4.32 (dd, 1H, J = 3.6, 12.0 Hz), 4.38 (dd, 1H, J = 3.0, 12.0 Hz),
4.55–4.72 (m, 8H), 5.03–5.07 (m, 2H), 5.11 (t, 1H, J = 9.6 Hz), 5.17–5.22 (m, 4H),
5.26 (br s, 2H), 5.40 (dd, 1H, J = 2.4, 7.8 Hz), 5.54 (d, 1H, J = 8.4 Hz), 6.32 (d, 1H,
J = 3.6 Hz), 7.21–7.35 (m, 20H); 13C NMR (150 MHz, CDCl3) d 20.6, 20.68, 20.7,
20.74, 20.78, 20.8, 20.9 and 21.0 (14 ꢂ CH3), 62.6 (CH2), 62.7 (CH2), 66.6 (CH),
67.5 (CH), 67.6 (CH), 67.8 (CH), 68.8 (CH), 69.5 (CH), 70.5 (CH), 70.8 (CH), 70.9
(CH), 71.4 (CH), 71.5 (CH), 73.0 (CH), 74.2 (CH2), 74.4 (CH2), 74.6 (CH2), 74.8
(CH2), 75.5 (CH), 75.8 (CH), 77.3 (CH), 80.3 (CH), 89.4 (CH), 91.9 (CH), 127.5,
127.6, 127.69, 127.73, 127.9, 128.0, 128.3, 128.4, 128.45 and 128.5 (20 ꢂ CH),
137.4 (C), 137.7 (C), 137.8 (C), 138.0 (C), 168.6, 168.9, 169.1, 169.2, 169.4,
169.5, 169.6, 170.1, 170.18, 170.24, 170.4 and 170.5 (14 ꢂ C); HRMS (ESI,
positive ion) Calcd for C38H46O17 Na m/z 797.2633. Found 797.2650.
Compound 15: reddish brown viscous liquid, ½a D25
ꢀ
+1.6 (c 0.19, CHCl3); IR
(neat): 1741, 1455, 1373, 1230, 1078, 1025, 741, 699 cmꢁ1
;
1H NMR (600 MHz,
C6D6): d 1.12 (s, 3H), 1.43 (s, 3H), 1.62 (s, 3H), 1.63 (s, 3H), 3.64 (dd, 1H, J = 5.4,
9.6 Hz), 3.73 (d, 1H, J = 3.6 Hz), 4.05 (dd, 1H, J = 6.0, 11.4 Hz), 4.25 (d, 1H,
J = 12.0 Hz), 4.31 (d, 1H, J = 12.0 Hz), 4.38 (d, 1H, J = 4.2 Hz), 4.39 (dd, 1H,
J = 4.2, 13.2 Hz), 4.44 (d, 1H, J = 12.0 Hz), 4.51 (d, 1H, J = 12.0 Hz), 4.71 (dd, 1H,
J = 3.0, 6.6 Hz), 5.75 (dd, 1H, J = 5.4, 6.0 Hz), 5.89–5.93 (m, 2H), 6.09 (dd, 1H,
J = 6.0, 15.6 Hz), 7.06–7.11 (m, 2H), 7.14–7.16 (m, 2H), 7.22 (t, 2H, J = 7.8 Hz),