An olefin cross metathesis approach to C-disaccharide analogs of the α-d-arabinofuranosyl-(1→5)-α-d-arabinofuranoside motif found in the mycobacterial cell wall

Article abstract of DOI:10.1016/j.tetlet.2006.05.008

Reported is the synthesis of a C-disaccharide analog of the α-d-Araf-(1→5)-α-d-Araf motif present in the cell wall of mycobacteria, including the human pathogen Mycobacterium tuberculosis. The key step is an olefin cross metathesis reaction that proceeds

Full text of DOI:10.1016/j.tetlet.2006.05.008

Tetrahedron Letters 47 (2006) 4561–4564
An olefin cross metathesis approach to C-disaccharide analogs
of the a-D-arabinofuranosyl-(1!5)-a-D-arabinofuranoside
motif found in the mycobacterial cell wall
Grace X. Chang and Todd L. Lowary*
Department of Chemistry, The Ohio State University, 100 West 18th Avenue, Columbus, OH 43210, USA
Received 4 January 2006; revised 28 April 2006; accepted 2 May 2006
Abstract—Reported is the synthesis of a C-disaccharide analog of the a-D-Araf-(1!5)-a-D-Araf motif present in the cell wall of
mycobacteria, including the human pathogen Mycobacterium tuberculosis. The key step is an olefin cross metathesis reaction that
proceeds in excellent yield and which can be carried out on mmol scale.
Ó 2006 Elsevier Ltd. All rights reserved.
Ethambutol (1, Fig. 1) is a front-line antibiotic used to
treat tuberculosis (TB).1 Like some of the other anti-
TB drugs, ethambutol acts by inhibiting the biosynthesis
of the mycobacterial cell wall.2 In particular, 1 inhibits
the arabinosyltransferases3 involved in the assembly of
the mycolyl-arabinogalactan (mAG) complex, the major
structural motif of the cell wall.4 Recent concern5 about
the resurgence of TB and the emergence of drug resis-
tant strains of Mycobacterium tuberculosis has led to
interest in the identification of new drugs that can be
used to treat this disease.6 Novel arabinosyltransferase
inhibitors have received special attention and work
in this area has involved both the synthesis of libraries
of ethambutol analogs,7 and the preparation of mimics
of various structural motifs in the arabinan portion of
the mAG complex.8 The arabinan moiety of this glyco-
conjugate consists of approximately 70 D-arabinofuran-
ose (D-Araf) residues attached via a-(1!5), a-(1!3) and
b-(1!2) linkages, with the a-(1!5)-linked motif (2)
predominating.4
HO
H
H
N
H3C
N
CH3
OH
H
H
1
O
O
HO
O
O(CH2)7CH3
O
O
O
O
HO
OH
HO
OH
HO
OH
HO
OH
2
3
Figure 1. Structures of ethambutol (1), the a-D-Araf-(1!5)-a-D-Araf motif present in the cell wall of mycobacteria (2) and the C-disaccharide analog
of 2 synthesized in this letter (3).
Keywords: C-Glycoside; Olefin metathesis; Mycobacteria; Arabinosyltransferase; Cell wall; Inhibitors.
*
Corresponding author at present address: Alberta Ingenuity Centre for Carbohydrate Science and Department of Chemistry, The University of
Alberta, Gunning-Lemieux Chemistry Centre, Edmonton, Canada AB T6G 2G2; e-mail: tlowary@ualberta.ca
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.05.008

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G. X. Chang, T. L. Lowary / Tetrahedron Letters 47 (2006) 4561–4564
C-Glycoside oligosaccharide analogs have been of long-
standing interest as synthetic targets.9 The attraction of
these compounds stems from the belief that C-glycosides
are better potential drug candidates because, compared
to their O-glycoside parents, they are not only more sta-
ble to acid, but also to glycosidases and thus will have
better biological half-lives. In the interest of developing
C-glycoside based arabinosyltransferase inhibitors, sev-
eral groups have reported the synthesis of C-glycoside
analogs of the a-D-Araf-(1!5)-a-D-Araf disaccharide
motif (2) in which the C–C bond between the monosac-
charide residues was formed either by a nitroaldol reac-
tion,10 a Wittig olefination,11 or an acetylide addition to
monosaccharide lactone.12 Very recently, Prandi and co-
workers synthesized a novel C-glycoside–azasugar con-
jugate and tested its ability to inhibit mycobacterial
growth.13 We describe here an alternate route to a C-
glycoside analog (3) of the a-D-Araf-(1!5)-a-D-Araf
disaccharide motif found in the mAG complex. In the
method reported here, the key step is an olefin cross
metathesis14 dimerization of a D-arabinofuranose de-
rived alkene.
boron trifluoride etherate in acetonitrile at 0 °C afforded
allyl C-glycoside 516 in 90% yield as a 10:1 a:b mixture
that could be separated by chromatography. The double
bond was then isomerized in 91% yield upon stirring a
solution of 5 in toluene with Ph(CH3CN)2Cl2 at 40 °C.
As expected, the trans alkene 617 was the major product
(coupling between the olefinic hydrogens = 15.8 Hz)
and only traces of the corresponding cis alkene could
1
be seen in the H NMR spectrum.
With 6 in hand, attempts were made to dimerize this
material using the first-generation Grubbs’ catalyst
(718). However, with this catalyst only unreacted 6 was
isolated and the decision was made to replace the benzo-
ate ester protecting groups with benzyl ethers. Thus,
treatment of 6 with sodium methoxide afforded 8,19
which was then alkylated upon treatment with benzyl
bromide and sodium hydride to give 920 (69% over
two steps). Dimerization of 9 with 7 gave only small
amounts (ꢀ10% yield) of the desired product 10. How-
ever, the use of the second-generation Grubbs’ catalyst
(1121) in dichloromethane at reflux22 provided a nearly
quantitative (96%) yield of 10.23 That the dimerization
had occurred was evident from the mass spectrum,
which showed a peak for the sodium adduct of 10
at m/z = 855.3870. In the 1H and 13C NMR spectra
The synthesis of 3 began from anomeric acetate 4
(Scheme 1), which was prepared as previously re-
ported.15 Treatment of 4 with allyltrimethylsilane and
O
O
BzO
RO
O
BzO
b
a
OAc
OBz
BzO
RO
OR
BzO
OBz
6, R = Bz
8, R = H
9, R = Bn
5
4
c
d
e
BnO
OBn
BnO
OBn
f
O
O
OBn
OR
BnO
R'O
O
O
BnO
BnO
OBn
OBn
10
12, R = R' = Bn
13, R = R' = H
14, R = H; R' = Tr
g, h
j
i
N
N
BnO
OBn
PCy3
Ru
Cl
Cl
Mes
Cl
Mes
Ph
Ph
Ru
PCy3
O
O(CH2)7CH3
RO
O
Cl
PCy3
7
11
BnO
OBn
15, R = Tr
16, R = H
l
k
5
Scheme 1. Reagents and conditions: (a) CH2@CHCH2Si(CH3)3, BF3–OEt2, CH3CN, 0 °C, 18 h, 90%; (b) Pd(CH3CN)2Cl2 (5 mol %), toluene, 40 °C,
24 h, 91%; (c) NaOCH3, CH3OH, rt, 2 h, 92%; (d) BnBr, NaH, DMF, rt, 19 h, 75%; (e) 11 (10 mol %), CH2Cl2, reflux, 18 h, 96%; (f) H2,
(Ph3P)3RhCl, toluene, 35 °C, 18 h, 81%; (g) Ac2O, HOAc, H2SO4, 0 °C, 30 min; (h) NaOCH3, CH3OH, rt, 10 h, 68% from 12; (i) TrCl, pyridine, rt,
12 h, 60%; (j) CH3(CH2)7I, NaH, DMF, rt, 1 h, 92%; (k) p-TsOH, CH2Cl2, CH3OH, rt, 2 h, 89%; (l) H2, Pd/C, CH2Cl2, CH3OH, rt, 16 h, 86%.

G. X. Chang, T. L. Lowary / Tetrahedron Letters 47 (2006) 4561–4564
4563
4. Brennan, P. J. Tuberculosis 2003, 83, 91–97.
of 10, the symmetry of the molecule was apparent. For
example, only eight peaks were present for the ring
and benzylic carbons in the 13C spectrum and only a sin-
5. (a) Nachega, J. B.; Chaisson, R. E. Clin. Infect. Dis. 2003,
36, S24–S30; (b) Wade, M. M.; Zhang, Y. Front. Biosci.
2004, 9, 975–994.
6. Recent reviews: (a) Kremer, L.; Besra, G. S. Expert Opin.
Inv. Drugs 2002, 11, 153–157; (b) Lowary, T. L. Mini-Rev.
Med. Chem. 2003, 3, 694–707; (c) Sharma, K.; Chopra, P.;
Singh, Y. Expert Opin. Ther. Targets 2004, 8, 79–93.
7. (a) Ha¨usler, H.; Kawakami, R. P.; Mlaker, E.; Severn, W.
1
gle olefinic hydrogen resonance was present in the H
NMR spectrum. Further support for the success of the
reaction was the absence of a peak corresponding to
the allylic methyl group in 9. This reaction could be car-
ried out on a 1.2 mmol scale, which bodes well for the
use of this approach in the synthesis of additional ana-
logs based on this C-disaccharide scaffold.
B.; Stutz, A. E. Bioorg. Med. Chem. Lett. 2001, 11, 1679–
¨
1681; (b) Lee, R. E.; Protopopova, M.; Crooks, E.;
Slayden, R. A.; Terrot, M.; Barry, C. E., III. J. Comb.
Chem. 2003, 5, 172–187; (c) Protopopova, M.; Hanrahan,
C.; Nikonenko, B.; Samala, R.; Chen, P.; Gearhart, J.;
Einck, L.; Nacy, C. A. J. Antimicrob. Chemother. 2005, 56,
968–974; (d) Jia, L.; Tomaszewski, J. E.; Noker, P. E.;
Gorman, G. S.; Glaze, E.; Protopopova, M. J. Pharm.
Biomed. Anal. 2005, 37, 793–799; (e) Jia, L.; Tomaszewski,
J. E.; Hanrahan, C.; Coward, L.; Noker, P. E.; Gorman,
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col. 2005, 144, 80–87.
Having successfully achieved the key C–C bond forming
reaction, the remainder of the steps in the sequence were
straightforward. First, hydrogenation of the alkene moi-
ety in 10 was achieved upon reaction with Wilkinson’s
catalyst and hydrogen gas at 35 °C in toluene, which
afforded the expected product 1224 in 81% yield. Conver-
sion of 12 into diol 1325 was accomplished first by ace-
tolysis26 of the benzyl ethers protecting the primary
hydroxyl groups (acetic anhydride/acetic acid/H2SO4
at 0 °C) and then cleavage of the resulting diacetate with
sodium methoxide (68% yield over two steps). Mono-
protection of 13 was achieved by reaction with chloro-
triphenylmethane in pyridine and the corresponding
trityl ether 1427 was isolated in 60% yield. Alkylation
of 14 with octyl iodide and sodium hydride gave a
92% yield of 15,28 which was then partially deprotected
by acid hydrolysis of the trityl ether. Alcohol 1629 was
obtained in an 89% yield. Conversion of 16 into the tar-
get compound 330 was carried out in 86% yield upon
treatment with hydrogen gas and 5% Pd/C in a 5:1 mix-
ture of methanol and dichloromethane.
8. (a) Cociorva, O. M.; Gurcha, S. S.; Besra, G. S.; Lowary,
T. L. Bioorg. Med. Chem. 2005, 13, 1369–1379; (b) Pathak,
A. K.; Pathak, V.; Suling, W. J.; Gurcha, S. S.;
Morehouse, C. B.; Besra, G. S.; Maddry, J. A.; Reynolds,
R. C. Bioorg. Med. Chem. Lett. 2002, 10, 923–928; (c)
Marotte, K.; Ayad, T.; Genisson, Y.; Besra, G. S.; Baltas,
M.; Prandi, J. Eur. J. Org. Chem. 2003, 2557–2565.
9. Selected reviews: (a) Postema, M. H. D.; Piper, J. L.;
Betts, R. L. Synlett 2005, 1345–1358; (b) Liu, L.; McKee,
M.; Postema, M. H. D. Curr. Org. Chem. 2001, 5, 1133–
1167; (c) Du, Y. G.; Linhardt, R. J.; Vlahov, I. R.
Tetrahedron 1998, 54, 9913–9959.
10. Gurjar, M. K.; Nagaprasad, R.; Ramana, C. V. Tetra-
hedron Lett. 2002, 43, 7577–7579.
11. Dondoni, A.; Marra, A. Tetrahedron Lett. 2003, 44, 4067–
4071.
In summary, we describe here the synthesis of a C-disac-
charide analog of the a-D-Araf-(1!5)-a-D-Araf motif
present in the mycobacterial mAG complex. The key
step in the synthesis is an olefin cross metathesis reaction
that proceeds in excellent yield and which can be carried
out on mmol scale. This route should therefore be ame-
nable to the preparation of large amounts of intermedi-
ates that are needed to synthesize additional analogs of
this motif, for example, through parallel synthesis. Such
analogs are potential inhibitors of mycobacterial arabi-
nosyltransferases and, in turn, are candidates for novel
anti-TB drugs.
12. Aslam, T.; Fuchs, M. G. G.; Le Formal, A.; Wightman,
R. H. Tetrahedron Lett. 2005, 46, 3249–3252.
13. Chaumontet, M.; Pons, V.; Marotte, K.; Prandi, J.
Tetrahedron Lett. 2006, 47, 1113–1116.
14. Blackwell, H. E.; O’Leary, D. J.; Chatterjee, A. K.;
Washenfelder, R. A.; Bussmann, D. A.; Grubbs, R. H.
J. Am. Chem. Soc. 2000, 122, 58–71.
15. Tolman, R. L.; Baker, D. A. Methods Carbohydr. Chem.
1976, 7, 59–62.
16. Data for 5: Syrup; [a]D +14.8 (c 1.0, CHCl3); Rf 0.42 (6:1
1
hexanes/EtOAc); H NMR (CDCl3, 400 MHz, dH) 8.02–
8.11 (m, 6H), 7.31–7.58 (m, 9H), 5.86–6.03 (m, 1H), 5.69
(t, 1H, J = 2.4 Hz), 5.57 (t, 1H, J = 2.4 Hz), 5.15–5.27 (m,
2H), 4.65–4.79 (m, 2H), 4.56–4.61 (m, 1H), 4.42–4.49 (m,
1H), 2.65 (t, 2H, J = 8.5 Hz); 13C NMR (CDCl3,
100 MHz, dC) 166.07, 165.43, 165.42, 133.42, 133.33,
133.09, 132.93, 129.65, 129.63, 129.02, 128.95, 128.48,
128.47, 128.46, 128.39, 128.38, 128.37, 128.20, 128.19,
128.18, 128.09, 128.08, 118.09, 82.77, 81.17, 80.90, 79.65,
64.02, 36.83; HR-ESI-MS calcd for [C29H26O7]Na+
830.4351, found: 830.4354.
Acknowledgment
The National Institutes of Health supported this work
through grant AI44045.
17. Data for 6: Syrup; [a]D +17.1 (c 1.0, CHCl3); Rf 0.40 (6:1
1
References and notes
hexanes/EtOAc); H NMR (CDCl3, 400 MHz, dH) 8.04–
8.11 (m 6H), 7.34–7.57 (m, 9H), 5.92 (dq, 1H, J = 15.8,
6.5 Hz), 5.75 (dd, 1H, J = 15.8, 8.2 Hz), 5.69 (t, 1H,
J = 2.5 Hz), 5.59 (t, 1H, J = 2.5 Hz), 4.69–4.81 (m, 3H),
4.57–4.63 (m, 1H), 1.76 (d, 3H, J = 6.5 Hz); 13C NMR
(CDCl3, 100 MHz, dC) 166.13, 165.52, 165.48, 133.41,
133.35, 132.96, 130.14, 129.97, 129.69, 129.66 (2C), 129.51
(2C), 129.09 (2C), 129.03, 128.41, 128.39, 128.26, 128.22,
128.13, 127.19, 126.47, 83.89, 81.56, 81.14, 79.21, 64.33,
17.71.
1. Bass, J. B., Jr.; Farer, L. S.; Hopewell, P. C.; Obrien, R.;
Jacobs, R. F.; Ruben, F.; Snider, D. E.; Thornton, G. Am.
J. Respir. Crit. Care Med. 1994, 149, 1359–1374.
2. Zhang, Y. Annu. Rev. Pharmacol. Toxicol. 2005, 45, 529–
564.
´
3. Belanger, A. E.; Besra, G. S.; Ford, M. E.; Mikusova, K.;
Belisle, J. T.; Brennan, P. J.; Inamine, J. M. Proc. Natl.
Acad. Sci. U.S.A. 1996, 93, 11919–11924.

4564
G. X. Chang, T. L. Lowary / Tetrahedron Letters 47 (2006) 4561–4564
18. Schwab, P.; France, M. B.; Ziller, J. W.; Grubbs, R. H.
Angew. Chem., Int. Ed. Engl. 1995, 34, 2039–2041.
19. Data for 8: Syrup; [a]D +3.6 (c 1.0, CH3OH); Rf 0.27 (10:1
CH2Cl2/CH3OH); 1H NMR (D2O, 400 MHz, dH) 5.80
(dq, 1H, J = 15.2, 6.3 Hz), 5.44 (dd, 1H, J = 15.2, 8.2 Hz),
4.04–4.08 (m, 1H), 3.94–3.99 (m, 1H), 3.78–3.82 (m, 2H),
3.57–3.68 (m, 2H), 1.65 (d, 3H, J = 6.3 Hz); 13C NMR
(D2O, 100 MHz, dC) 133.46, 128.09, 83.15, 82.10, 80.33,
76.33, 61.63, 17.47; HR-ESI-MS calcd for [C8H14O4]Na+
197.0784, found 197.0783.
3.82 (m, 2H), 3.64–3.67 (m, 4H), 2.39 (broad s, 2H), 1.47–
1.82 (m, 4H); 13C NMR (CDCl3, 100 MHz, dC) 137.65
(2C), 137.57 (2C), 128.42 (4C), 128.41 (4C), 127.83 (2C),
127.80 (2C), 127.69 (4C), 127.64 (4C), 87.32 (2C), 84.44
(2C), 82.67 (2C), 82.13 (2C), 72.02 (2C), 71.69 (2C), 62.73
(2C), 28.98 (2C); HR-ESI-MS calcd for [C40H46O8]Na+
677.3085, found 877.3081.
26. Subramanian, V.; Lowary, T. L. Tetrahedron 1999, 55,
5965–5976.
27. Data for 14: Syrup; [a]D +28.9 (c 1.0, CHCl3); Rf 0.14 (6:1
1
20. Data for 9: Syrup; [a]D +2.5 (c 1.1, CHCl3); Rf 0.48 (6:1
hexanes/EtOAc); H NMR (CDCl3, 400 MHz, dH) 7.16–
1
hexanes/EtOAc); H NMR (CDCl3, 400 MHz, dH) 7.22–
7.46 (m, 35H), 4.40–4.52 (m, 8H), 4.16–4.22 (m, 1H),
3.97–4.10 (m, 6H), 3.77–3.84 (m, 2H), 3.65–3.68 (m, 2H),
3.17–3.30 (m, 2H) 1.45–1.82 (m, 4H); 13C NMR (CDCl3,
100 MHz, dC) 143.95 (3C), 137.89, 137.73 (2C), 137.63,
128.74 (4C), 128.47 (4C), 128.44 (4C), 128.38 (4C), 128.35
(4C), 127.78 (2C), 127.77, 127.73 (2C), 127.72 (2C),
127.68, 127.67, 127.66, 127.65 (2C), 126.97, 126.96,
126.95, 88.05, 87.35, 87.30, 86.74, 85.31, 85.32, 84.52,
82.61, 82.42, 81.83, 81.70, 77.20, 72.09, 71.78, 64.32, 62.86,
29.16.
7.35 (m, 15H), 5.80 (dq, 1H, J = 15.2, 6.2 Hz), 5.65
(dd, 1H, J = 15.2, 8.0 Hz), 4.51–4.59 (m, 6H), 4.35–4.40
(m, 1H), 4.15–4.22 (m, 1H), 4.06–4.11 (m, 1H), 3.89–3.94
(m, 1H), 3.55–3.61 (m, 2H), 1.71 (d, 3H, J = 6.2 Hz); 13C
NMR (CDCl3, 100 MHz, dC) 138.11, 137.93, 137.86,
129.70 (4C), 129.67 (2C), 128.33 (2C), 128.28 (3C), 127.72
(2C), 127.65 (3C), 127.52, 88.13, 84.84, 83.19, 80.90,
73.31, 71.97, 71.89, 70.29, 18.29; HR-ESI-MS calcd for
[C29H32O4]Na+ 467.2193, found 467.2190.
21. Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett.
1999, 1, 953–956.
28. Data for 15: Syrup; [a]D +16.4 (c 0.9, CHCl3); Rf 0.35
(10:1 hexanes/EtOAc); 1H NMR (CDCl3, 400 MHz, dH)
7.21–7.45 (m, 35H), 4.39–4.59 (m, 8H), 4.17–4.20 (m,
1H), 4.11–4.15 (m, 1H), 4.05–4.08 (m, 1H), 3.91–4.00 (m,
3H), 3.76–3.80 (m, 2H), 3.39–3.54 (m, 4H), 3.18–3.29 (m,
2H), 1.25–1.63 (m, 16H), 0.87 (t, 3H, J = 7.0 Hz); 13C
NMR (CDCl3, 100 MHz, dC) 143.97 (2C), 143.93, 138.07,
138.00, 137.94 (2C), 128.75 (5C), 128.37 (5C), 127.77
(5C), 127.69 (5C), 127.66 (4C), 127.64, 127.63 (3C)
127.62, 127.61, 126.94 (2C), 126.93 (2C), 126.94, 88.44,
88.43, 88.00, 87.99, 86.72, 86.73, 85.65, 85.46, 82.26,
82.25, 81.63, 81.13, 71.81, 71.74, 70.95, 64.34, 33.52,
33.50, 31.83, 30.27, 29.43, 29.26, 26.13, 22.65, 14.09; HR-
ESI-MS calcd for [C67H76O8]Na+ 1031.5432, found
1031.5429.
22. Olefin metathesis procedure: Catalyst 11 (97 mg,
10 mol %) was added, in a dry box, to a solution of 9
(530 mg, 1.2 mmol) in dry CH2Cl2 (15 mL). The flask was
removed from the dry box and the solution was heated at
reflux under argon for 18 h, before being cooled and
concentrated under vacuum. Column chromatography
(4:1 hexanes/EtOAc) of the resulting residue gave 10
(461 mg, 96%).
23. Data for 10: Syrup; [a]D +0.3 (c 1.0, CHCl3); Rf 0.29
(3:1 hexanes/EtOAc); 1H NMR (CDCl3, 400 MHz, dH)
7.24–7.32 (m, 30H), 5.89 (br s, 2H), 4.44–4.55 (m, 14H),
4.20 (dd, 2H, J = 4.8 Hz, 10.1 Hz), 4.06–4.08 (m, 2H), 3.92
(dd, 2H, J = 1.2 Hz, 5.0 Hz), 3.56 (d, 4H, J = 5.4 Hz); 13
C
NMR (CDCl3, 100 MHz, dC) 138.15 (2C), 137.92 (2C),
137.77 (2C), 130.77 (2C), 128.38 (4C), 128.34 (4C), 128.32
(4C), 127.73 (6C), 127.70 (4C), 127.65 (4C), 127.57 (4C),
88.28 (2C), 84.82 (2C), 82.22 (2C), 81.25 (2C), 73.36 (2C),
72.10 (2C), 71.87 (2C), 70.25 (2C); HR-ESI-MS calcd for
[C54H56O8]Na+ 855.3867, found 855.3870.
29. Data for 16: Syrup; [a]D +26.3 (c 0.8, CHCl3); Rf 0.41 (2:1
1
hexanes/EtOAc); H NMR (CDCl3, 400 MHz, dH) 7.25–
7.35 (m, 20H), 4.49–4.60 (m, 8H), 4.12–4.19 (m, 1H),
4.02–4.10 (m, 1H), 3.93–4.00 (m, 4H), 3.75–3.82 (m, 2H),
3.66–3.71 (m, 2H), 3.42–3.55 (m, 4H), 2.04 (s, 1H), 1.23–
1.68 (m, 16H), 0.87 (t, 3H, J = 7.0 Hz); 13C NMR (CDCl3,
100 MHz, dC) 137.98, 137.90, 137.68, 137.60, 128.71 (3C),
128.48 (2C), 128.46 (3C), 128.38 (2C), 127.87 (3C), 127.78
(2C), 127.73 (3C), 127.68 (2C), 87.95, 87.31, 85.56, 84.48,
82.72, 82.63, 82.20, 81.13, 73.30, 72.08, 71.81, 71.71, 72.61,
70.93, 62.82, 32.89, 31.79, 29.62, 29.39, 29.26, 26.77, 26.11,
22.64, 14.08.
24. Data for 12: Syrup; [a]D +13.3 (c 1.0, CHCl3); Rf 0.29 (3:1
1
hexanes/EtOAc); H NMR (CDCl3, 400 MHz, dH) 7.18–
7.33 (m, 30H), 4.44–4.54 (m, 12H), 4.18 (dd, 2H,
J = 3.9 Hz, 5.8 Hz), 4.00–4.05 (m, 4H), 3.78–3.82 (m,
2H), 3.50–3.61 (m, 4H), 1.50–1.90 (m, 4H); 13C NMR
(CDCl3, 100 MHz, dC) 138.16 (2C), 137.91 (2C), 137.87
(2C), 128.30 (6C), 128.26 (4C), 128.05 (4C), 127.69 (4C),
127.63 (4C), 127.62 (4C), 127.49 (4C), 88.34 (2C), 85.94
(2C), 82.52 (2C), 81.73 (2C), 73.82 (2C), 72.26 (2C), 72.23
(2C), 70.80 (2C), 29.76 (2C); HR-ESI-MS calcd for
[C54H58O8]Na+ 857.4024, found 857.4020.
30. Data for 3: Syrup; [a]D +46.0 (c 0.9, CH3OH); Rf 0.17 (8:1
CH2Cl2/CH3OH); 1H NMR (D2O, 400 MHz, dH) 3.44–
3.95 (m, 14H), 1.51–1.57 (m, 6H), 1.20–1.22 (m, 10H), 0.79
(t, 3H, J = 7.0 Hz); 13C NMR (D2O, 100 MHz, dC) 85.51,
82.50, 82.16, 81.41, 80.69, 80.70, 78.08, 77.21, 72.05, 70.99,
61.62, 32.01, 32.00, 29.53, 29.44, 29.38, 28.79, 26.05, 22.80,
14.12; HR-ESI-MS calcd for [C20H38O8]Na+ 429.2459,
found 429.2457.
25. Data for 13: Syrup; [a]D +17.1 (c 1.1, CHCl3); Rf 0.21 (1:1
1
hexanes/EtOAc); H NMR (CDCl3, 400 MHz, dH) 7.23–
7.46 (m 20H), 4.45–4.52 (m, 8H), 3.96–4.10 (m, 6H), 3.80–