Synthesis of tricolorin F

Article abstract of DOI:10.1021/jo030244c

A hetero-trisaccharide resin glycoside of jalapinolic acid known as tricolorin F has been synthesized. The approach involved the preparation of intermediate 5 and a subsequent coupling reaction with imidate 6 to produce disaccharide 7, which after deacety

Full text of DOI:10.1021/jo030244c

VOLUME 69, NUMBER 14
J ULY 9, 2004
© Copyright 2004 by the American Chemical Society
Syn th esis of Tr icolor in F
Marco Brito-Arias,1 Rogelio Pereda-Miranda,2 and Clayton H. Heathcock*,3
Center for New Directions in Organic Synthesis,† Department of Chemistry, University of California,
Berkeley, California 94720, Unidad Profesional Interdisciplinaria de Biotecnolog´ıa, Instituto Polite´nico
Nacional, Av. Acueducto s/ n Barrio La Laguna Ticoma´n, Mexico City 07340, Mexico, and Departamento
de Farmacia, Facultad de Qu´ımica, Universidad Nacional Autonoma de Me´xico, Ciudad Universitaria,
Mexico City 04510, Mexico
heathcock@cchem.berkeley.edu
Received J uly 29, 2003
A hetero-trisaccharide resin glycoside of jalapinolic acid known as tricolorin F has been synthesized.
The approach involved the preparation of intermediate 5 and a subsequent coupling reaction with
imidate 6 to produce disaccharide 7, which after deacetylation generated intermediate 8. A further
coupling between this glycosyl acceptor and the quinovose glycosyl donor 9 resulted in the formation
of the tricoloric acid C derivative 10. Basic hydrolysis afforded the intermediate 11, which was
subsequently lactonized under Yamaguchi conditions to produce protected macrolactone 12. Removal
of acetonide and benzyl protecting groups afforded pure tricolorin F (1).
Resin glycosides, biodynamic constituents of the morn-
ing glory species [e.g., Ipomoea genus (Convolvulaceae
family)], are amphipatic glycosyl derivatives of monohy-
droxy and dihydroxy C14 and C16 fatty acids. The
hydrophilic moieties (sugar core) may simultaneously be
composed of homo- and heteropolysaccharides linked to
the hydrophobic aglycon. Sugar units found in these
metabolites are epimers of hexoses (mainly D-glucose) and
pentoses (L-rhamnose, D-fucose, and D-quinovose), with
D-Glc-(12)-D-Fuc representing a highly conserved disac-
charide subunit. Most of them contain jalapinolic acid,
11(S)-hydroxyhexadecanoic acid, as the aglycon which in
turn is always tied back to form a macrolactone ring
spanning two, three, or more units of their saccharide
backbones.4 Several biological activities have been de-
scribed for the convolvulaceous resins, including antimi-
crobial, mammalian cytotoxicity, and plant toxicity,
among others. Pharmacologically, the crude MeOH-
soluble resin extracts from several Mexican Ipomoea
species, commonly known as jalaps, constitute a group
of traditionally valued purgative remedies. It has been
demonstrated that all the activities are associated with
the macrocyclic structure of these lipopolysaccharides,
since the glycosidic acids derived from saponification
have shown to be inactive.4
The ability of Ipomea tricolor to inhibit the growth of
invasive weeds has been attributed to a mixture of these
resin glycosides.4,5 From the chloroform-soluble extract
of this plant material a complex glycolipids mixture has
been isolated and purified by recycling HPLC, from which
tricolorins A-J have been fully characterized by means
of high-resolution NMR spectrometry and FAB-mass
spectrometry.6,7 From the chloroform-soluble extract
the most abundant and easy to purify resin was tri-
colorin A.5
† The Center for New Directions in Organic Synthesis is supported
by Bristol-Myers Squibb as Sponsoring Member and Novartis as
Supporting Member.
(1) Permanent address: Instituto Polite´cnico Nacional.
(2) Universidad Nacional Auto´noma de Me´xico.
(3) University of California.
This was the first tricolorin to be fully characterized
and was subsequently synthesized by Larson and Heath-
(5) Pereda-Miranda, R.; Mata, R.; Anaya, A. L.; Wickramaratne, D.
B. M.; Pezzuto, J . M.; Kinghorn, A. D. J . Nat. Prod. 1993, 56, 571-
582.
(4) Pereda-Miranda, R.; Bah, M. Curr. Top. Med. Chem. 2003, 3,
111-131.
10.1021/jo030244c CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/06/2004
J . Org. Chem. 2004, 69, 4567-4570
4567

Brito-Arias et al.
SCHEME 1 a
a
Key: (a) BF3‚Et2O, CH2Cl2, -20 °C, 1 h; (b) NaOMe, MeOH, 4 h, rt; (c) 2,4,6-trichlorobenzoyl chloride, Et3N, DMAP, benzene; (d) H2,
10% Pd(OH)2/C, 10% HCl-MeOH, MeOH.
cock8 and by Lu et al.,9 using a macrolactonization
approach, and by Fu¨rstner and Mu¨ller,10 employing a
ring-closing-metathesis strategy.
ester and coupled with the known tri-O-acetyl-R-D-
fucopyranosyl imidate in the presence of BF3‚Et2O
(Scheme 1). The resulting glycoside was deacetylated and
trasformed to the glycosyl acceptor 5.8,9 The next reaction
sequence involved the preparation of known glycosyl
donor 2-O-acetyl-3,4,6-tri-O-benzyl-D-glucopyranosyl imi-
date 6,12 which was chosen as a glycosyl donor because
it can be selectively deprotected under basic conditions
at position 2, the point of attachment for the quinovose
glycosyl acceptor. The coupling reaction between 5 and
6 in the presence of BF3‚Et2O produced disaccharide 7
in 70% yield. That 7 had the desired â-configuration at
the new glycosidic linkage was shown by the observed
The approach followed by Bah and Pereda-Miranda7
for establishing the structure of tricolorin F was to carry
out acid-catalyzed hydrolysis, which indicated that the
aglycon fragment corresponds to (11S)-hydroxyhexa-
decanoic acid (jalapinolic acid) and the trisaccharide
fragment was composed of D-fucose (6-deoxy-D-galactose),
D-glucose, and D-quinovose (6-deoxy-D-glucose). Because
of signal overlapping in the region δ 3.5-4.5, it was
necessary to peracetylate tricolorin F to fully resolve its
1H NMR spectrum. The interglycosidic connectivities and
site of lactonization were established on the basis of the
observed 13C-1H long-range cross-peaks (2,3J CH) in the
HMBC experiments. Through this analysis, it was de-
duced that the structure of tricolorin F is (11S)-hydroxy-
hexadecanoic acid 11-O-â-D-quinovopyranosyl-(1f2)-O-
â-D-glucopyranosyl-(1f2)-â-D-fucopyranoside 1,2′′′-lactone
(1).
4,7
3J H-H values between glucose H-1 (δ 4.73, d, J 1,2 ) 8.0
Hz) and H-2 (δ 4.95, dd, J 2,3 ) 8.0 Hz). Methanolysis of
the acetyl group produced glycosyl acceptor 8 in quan-
titative yield.
The third sugar residue was the synthetically chal-
lenging quinovose, which was subsequently transformed
to the glycosyl donor 2-O-acetyl-3,4-di-O-benzyl-R-D-
quinovosyl trichoroacetimidate 9 following a procedure
similar to the one described for the synthesis of a
rhamnosyl analogue. The coupling reaction between 8
and 9 under the influence of BF3‚Et2O afforded trisacca-
haride 10. Again, the â-anomeric configuration for the
new glycosidic bond was confirmed by the vicinal coupling
Our synthetic approach started with naturally occur-
ring jalapinolic acid,11 which was converted to the methyl
(6) Bah, M.; Pereda-Miranda, R. Tetrahedron 1996, 52, 13063-
13080.
(7) Bah, M.; Pereda-Miranda, R. Tetrahedron 1997, 53, 9007-9022.
(8) (a) Larson, D. P.; Heathcock, C. H. J . Org. Chem. 1996, 61, 5208-
5209. (b) Larson, D. P.; Heathcock, C. H. J . Org. Chem. 1997, 62, 8406-
8418.
(11) (S)-Hydroxyhexadecanoic acid (jalapinolic acid) is available by
hydrolysis of the crude convolvulaceous resins (ref 4) and also by total
synthesis (ref 8).
(12) Schmidt, R. R.; Effenberger, G. Carbohydr. Res. 1987, 171, 59-
79.
(9) Lu, S.-F.; O’Yang, Q. Q.; Guo Z-W.; Yu, B.; Hui, Y.-Z. J . Org.
Chem. 1997, 62, 8400-8405.
(10) Fu¨rstner A.; Mu¨ller, T. J . Org. Chem. 1998, 63, 424-425.
4568 J . Org. Chem., Vol. 69, No. 14, 2004

Synthesis of Tricolorin F
4], 4.16 (dd, J ) 7.5, 7.5, 1H) [Fuc-2], 4.31 (d, J ) 7.5, 1H)
[Fuc-1], 4.47 (d, J ) 12.0, 1H), 4.53 (brd, 2H), 4.62 (d, J )
12.0, 1H), 4.78 (d, J ) 12.0, 1H), 4.83 (d, J ) 11.0, 1H), 5.01
(d, J ) 11.0, 1H), 7.10-7.51 (m, 15H); 13C NMR (CDCl3) δ 14.5,
16.8, 23.0, 25.0, 25.3, 25.5, 26.5, 28.3, 29.3, 29.6 (x2), 29.8, 29.9,
32.1, 33.8, 34.5 (x2), 51.5 68.8, 69.0, 71.5, 72.3, 73.5, 75.0 (x2),
75.8, 76.0, 78.5, 79.0, 79.8, 84.0, 100.0, 103.8, 109.5, 127.4,
127.6, 127.7, 127.8, 128.2, 128.4, 138.1, 138.2, 138.3, 174.2;
negative-ion HRFAB-MS m/z 903.5260 [M - H] (calcd for
between quinovose H-1 (δ 5.29, d, J 1,2 ) 8.0 Hz) and H-2
(δ 5.48, dd, J 2,3 ) 9.6 Hz). Basic hydrolysis of the acetate
and methyl ester gave tricoloric acid C (11).
The critical lactonization step was achieved following
the Yamaguchi protocol, providing protected tricolorin F
(12). Removal of the acetonide and benzyl groups was
accomplished by hydrogenolysis under acidic conditions
1
to obtain synthetic tricolorin F (1) identical by H and
13C NMR with an authentic sample of the natural
product.4
C
53H75O12 903.5258).
Meth yl 11(S)-11-[[2-O-Acetyl-3,4-d i-O-ben zyl-â-D-qu in o-
vosyl)-(1f2)-(3,4,6-t r i-O-b e n zyl-â-D -glu cop yr a n osyl)-
(1f2)-3,4-O-isop r op ylid en e-â-D-fu cop yr a n osyl]oxy]h exa -
d eca n oa te (10). Compound 8 (32 mg, 0.035 mmol) and
imidate 9 (19 mg, 0.035 mmol) were coevaporated with freshly
distilled benzene. The oily residue was dissolved in 1.5 mL of
CH2Cl2, and the resulting solution was cooled to -20 °C and
then treated with ethereal BF3‚Et2O (0.25 M, 0.05 mL). The
resulting mixture was stirred for 1 h under N2, the reaction
was then quenched by the addition of saturated aqueous
NaHCO3, and the resulting mixture was extracted with
CH2Cl2. The organic phase was dried over Na2SO4 and
evaporated with a rotary evaporator. Purification by chroma-
tography, eluting with 20% EtOAc in hexanes, gave 27 mg
(60%) of 10 as a syrup: [R]D -14 (c 7.3, CH2Cl2); IR (thin film)
Exp er im en ta l Section
Gen er a l Meth od s. Unless otherwise stated, 1H and 13C
NMR spectra were recorded in CDCl3 and C5D5N solution at
400 and 125 MHz, respectively. Coupling constants (J ) are
reported in Hz. Specific rotations were measured in CH2Cl2
at rt. Reagents and solvent were used as received from
commercial suppliers. All intermediates were purified by flash
chromatography on silica gel and eluted with EtOAc in
hexanes. Reaction progress was monitored on glass silica gel
60 (E. Merck), heating after dipping in CAM solution ((NH4)6-
Mo7O24‚6H2O (5 g) and Ce(SO4)2 (100 mg) in 5% aq H2SO4 (100
mL)).
1
1747 cm-1; H NMR (C5D5N) δ 0.84 (t, J ) 7.0, 3H) [J al-16],
Met h yl (11S)-11-[[(2-O-Acet yl-3,4,6-t r i-O-b en zyl-â-D-
glu cop yr a n osyl)-(1f2)-3,4-O-isop r op ylid en e-â-D-fu cop y-
r a n osyl]oxy]h exa d eca n oa te (7). Alcohol 5 (50 mg, 0.108
mmol) and imidate 6 (68 mg, 0.108 mmol) were coevaporated
in freshly distilled benzene, and the oily residue was dissolved
in 1 mL of CH2Cl2, and cooled to -20 °C. After careful addition
of BF3‚Et2O (0.25 M in Et2O, 0.1 mL), the reaction was allowed
to proceed for 1 h. The reaction mixture was treated with a
saturated solution of NaHCO3 and the resulting mixture
extracted with CH2Cl2. The organic phase was dried over
Na2SO4, filtered, and evaporated in vacuo. Purification by
chromatography on silica gel, eluting with 20% EtOAc in
hexanes, gave 60 mg (70%) of compound 7 as an oil: [R]D -15
1.22-1.40 (m, 20H), 1.48-1.51 (m, 4H), 1.40 (s, 3H), 1.50 (d,
J ) 6.1, 3H) [Qui-6], 1.52 (d, J ) 6.5, 3H) [Fuc-6], 1.56 (s, 3H),
2.02 (s, 3H), 1.60-1.66 (m, 3H), 2.31 (t, J ) 7.5, 2H) [J al-2],
3.45 (dd, J ) 9.2, 9.2, 1H) [Qui-4], 3.61 (s, 3H), 3.66 (dq, J )
6.2, 9.3, 1H) [Qui-5], 3.73 (m, 1H) [Glu-5], 3.83-4.03 (m, 6H),
4.07 (dd, J ) 7.5, 8.0, 1H) [Glu-2], 4.22 (dd, J ) 2.0, 6.0, 1H)
[Fuc-4], 4.35 (dd, J ) 6.2, 7.1, 1H) [Fuc-3], 4.66 (d, J ) 11.3,
1H), 4.70-4.74 (m, 5H), 4.83 (d, J ) 11.3, 1H), 4.85 (d, J )
11.3, 1H), 4.96 (d, J ) 11.3, 1H), 4.98 (d, J ) 11.3, 1H), 5.04
(d, J ) 11.3, 1H), 5.14 (d, J ) 11.3, 1H), 5.29 (d, J ) 8.0, 1H)
[Qui-1], 5.40 (d, J ) 7.5, 1H) [Glu-1], 5.48 (dd, J ) 8.0, 9.6,
1H) [Qui-2], 7.14-751 (m, 25H); 13C NMR (C5D5N) δ 12.8, 15.7,
16.9, 19.5, 21.4, 23.8 (x2), 24.1, 24.9, 26.5, 27.9, 28.3, 28.5, 28.7,
29.0, 30.7, 32.6, 33.3, 33.8, 50.0, 67.2, 67.6, 70.4, 71.9, 72.9,
73.3, 73.7, 73.9, 74.0, 74.1, 75.2, 75.4, 77.4, 77.8, 78.2, 79.5,
82.2, 82.5, 83.7, 98.1, 99.4, 99.8, 108.2, 127.3, 127.5, 128.5,
138.9, 168.4, 172.4; negative-ion HRFAB-MS m/z 1271.6885
[M - H] (calcd for C75H99O17 m/z 1271.6882).
11(S)-11-[[2-O-Acetyl-3,4-d i-O-ben zyl-â-D-qu in ovosyl)-
(1f2)-(3,4,6-tr i-O-ben zyl-â-D-glu cop yr a n osyl)-(1f2)-3,4-
O-isop r op ylid en e-â-D-fu cop yr a n osyl]oxy]h exa d eca n o-
ic Acid (11). A solution of compound 10 (20 mg, 0.015 mmol)
and KOH (10 mg) in CH3OH-H2O (4 mL, 9:1 v/v) was refluxed
for 4 h. The resulting solution was dissolved in 5 mL of
CH2Cl2 and washed with 1 M HCl (1 × 5 mL), dried over
Na2SO4 and evaporated. Purification by chromatography,
eluting with 20% EtOAc in hexanes, gave 15 mg (80%) of acid
11 as a syrup: [R]D -8 (c ) 0.90, CH2Cl2); IR (CH2Cl2 solution)
3430, 1710 cm-1; 1H NMR (C5D5N) δ 0.79 (t, J ) 7.0, 3H) [J al-
16], 1.18-1.25 (m, 20H), 1.34 (s, 3H), 1.47 (d, J ) 6.5, 3H)
[Fuc-6], 1.48 (d, J ) 6.1, 3H) [Qui-6], 1.53 (s, 3H), 1.57 (m,
3H), 1.65 (m, 2H), 2.45 (t, J ) 7.5, 2H) [J al-2], 3.37 (dd, J )
9.0, 9.0, 1H) [Qui-4], 3.62 (dq, J ) 6.1, 9.0, 1H), [Qui-5], 3.70
(m, 1H) [Glu-5], 3.79 (quintet, J ) 6.0, 1H) [J al-11], 3.95-
3.80 (m, 6H), 3.99 (dd, J ) 7.7, 8.5, 1H) [Qui-2], 4.12 (dd, J )
2.0, 6.5, 1H) [Fuc-4], 4.14 (dd, J ) 7.2, 8.5, 1H) [Glu-2], 4.31
(dd, J ) 6.5, 7.5, 1H) [Fuc-3], 4.67 (d, J ) 7.5, 1H) [Fuc-1],
4.63 (d, J ) 12.0, 1H), 4.66 (d, J ) 12.0, 1H), 4.68 (d, J ) 12.0,
1H), 4.69 (dd, J ) 6.5, 7.5, 1H) [Fuc-2], 4.71 (d, J ) 11.2, 1H),
4.79 (d, J ) 11.2, 1H), 4.99 (d, J ) 10.5, 1H), 5.01 (d, J ) 10.3,
1H), 5.03 (d, J ) 11.5, 1H), 5.15 (d, J ) 7.7, 1H) [Qui-1], 5.31
(d, J ) 11.5, 1H), 5.33 (d, J ) 10.3, 1H), 5.40 (d, J ) 7.2, 1H)
[Glu-1], 6.97-7.66 (m, 25H); 13C NMR (C5D5N) δ 14.1, 17.6,
18.4, 22.5, 22.6, 24.9, 25.3, 25.6, 26.5, 27.7, 29.3, 29.6, 29.9,
29.5, 30.1, 31.9, 34.5, 34.9, 37.4, 68.3, 69.2, 71.4, 73.2, 74.4,
74.7, 74.8, 75.3, 75.8, 76.5, 76.8, 78.5, 79.5, 80.4, 83.4, 85.2,
(c 1.8, CH2Cl2); IR (thin film) 1742 cm-1; H NMR (CDCl3) δ
1
0.89 (t, J ) 7.0, 3H) [J al-16], 1.22-1.43 (m, 20H), 1.28 (s, 3H),
1.33 (d, J ) 6.5, 3H) [Fuc-6], 1.39-1.49 (m, 5H), 1.44 (s, 3H),
1.50-1.59 (m, 2H), 1.97 (s, 3H), 2.26 (t, J ) 7.5, 2H) [J al-2],
3.42 (brd, J ) 10.0, 1H) [Glu-5], 3.53 (quintet, J ) 6.0, 1H)
[J alp-11], 3.63 (s, 3H), 3.78-3.65 (m, 6H), 3.92 (dd, J ) 1.9,
5.7, 1H) [Fuc-4], 4.03 (dd, J ) 6.0, 7.0, 1H), 4.26 (d, J ) 7.0
Hz, 1H) [Fuc-1], 4.52 (d, J ) 12.0, 1H), 4.58 (d, J ) 11.0, 1H),
4.64 (d, J ) 12.0, 1H), 4.66 (d, J ) 11.0, 1H), 4.73 (d, J ) 8.0,
1H) [Gluc-1], 4.74 (d, J ) 11.0, 1H), 4.77 (d, J ) 11.0, 1H),
4.95 (dd, J ) 8.0, 8.0, 1H) [Glu-2], 7.10-7.51 (m, 15H); 13C
NMR (CDCl3): δ 14.1, 16.7, 21.0, 22.6, 24.7, 25.0, 25.2, 26.3,
27.8, 29.1, 29.3, 29.6, 29.8, 29.9, 32.1, 33.8, 34.2, 34.7, 51.4,
68.2, 68.5, 73.4, 73.6, 74.6, 74.8, 75.3, 76.3, 78.0, 78.9, 79.4,
79.8, 83.0, 100.0, 100.4, 109.5, 127.4, 127.6, 127.7, 127.8, 128.2,
128.4, 138.1, 138.2, 138.3, 169.4, 174.2; negative-ion HRFAB-
MS m/z 945.5368 [M - H] (calcd for C55H77O13 m/z 945.5364).
Meth yl (11S)-11-[[(3,4,6-Tr i-O-ben zyl-â-D-glu cop yr a n o-
syl)-(1f2)-3,4-O-isop r op ylid en e-â-D-fu cop yr a n osyl]oxy]-
h exa d eca n oa te (8). Compound 7 (50 mg, 0.053 mmol) was
dissolved in anhydrous MeOH (1 mL), and a methanolic
sodium methoxide solution (8 mg of Na in 1 mL MeOH) was
added dropwise. The solution was stirred at rt under N2
atmosphere for 4 h. The reaction solution was diluted with
CH2Cl2, washed with cold 1 M HCl (10 mL), saturated solution
of NaHCO3 (2 × 10 mL), and water (1 × 10 mL), dried over
Na2SO4, and evaporated with a rotary evaporator. Purification
by chromatography on silica gel, eluting with 20% EtOAc in
hexanes, gave 45 mg (95%) of an oily product: IR (thin film)
3500, 1738 cm-1; [R]D -6.8 (c 3.5, CH2Cl2); 1H NMR (CDCl3) δ
0.88 (t, J ) 6.5, 3H) [J al-16], 1.22-1.40 (m, 20H), 1.34 (s, 3H),
1.37 (d, J ) 6.5, 3H) [Fuc-6], 1.46-1.53 (m, 2H), 1.53 (s, 3H),
1.60 (m, 2H), 2.28 (t, J ) 7.5, 2H) [J al-2], 3.65 (s, 3H), 3.59-
3.71 (m, 5H), 3.75-3.79 (m, 2H), 4.00 (brd, J ) 5.5, 1H) [Fuc-
J . Org. Chem, Vol. 69, No. 14, 2004 4569

Brito-Arias et al.
85.4, 99.5, 100.9, 103.6, 109.6, 127.2, 127.5, 128.2, 128.5, 138.9,
178.1; negative-ion HRFAB-MS m/z 1215.6646 [M - H]- (calcd
for C72H95O16 m/z 1215.6620).
back-filled with H2, and stirred overnight under the pressure
of a balloon filled with H2. The reaction mixture was basified
with 0.5 mL of Et3N and filtered through a small plug of Celite.
Purification by chromatography was performed with a short
column, eluting with 10:10:1 acetone-chloroform-methanol,
to give 7 mg (80%) of tricolorin F (1) as a white solid: mp 116-
118 °C; [R]D -30 (c ) 0.1, MeOH); 1H NMR (C5D5N) δ 0.85 (t,
J ) 7, 3H), 1.20-1.70 (m, 30H), 1.55 (d, J ) 6.1, 1H), 1.72(d,
J ) 5.8, 1H), 2.42-2.60 (m, 2H), 3.77 (m, 2H), 3.81 (m, 2H),
3.94 (m, 1H), 4.05-4.09 (m, 2H), 4.17-4.20 (m, 4H), 4.36-
4.38 (m, 2H), 4.74 (d, J ) 7.5, 1H) [Fuc-1], 5.23 (d, J ) 7.5,
1H) [Glu-1], 5.23 (d, J ) 7.5, 1H) [Qui-1], 5.65 (dd, J ) 7.5,
8.5, 1H) [Qui-2]; 13C NMR (C5D5N) δ 13.8, 16.9, 17.8, 18.8, 22.5,
25.2, 28.5, 29.0, 32.0, 35.1, 63.6, 71.3, 73.6, 74.7, 75.5, 76.2,
81.1, 103.0, 173.2; positive-ion HRFAB-MS m/z 731.3833 [M
+ Na]+ (calcd for C34H60O15Na m/z 731.3829). The spectra
were identical with those of an authentic sample of natural
tricolorin F.7
11(S )-11-[[3,4-D i-O -b e n zy l-â-D -q u in o v o s y l)-(1f2)-
(3,4,6-t r i-O-b en zyl-â-D-glu cop yr a n osyl)-(1f2)-3,4-O-iso-
p r op ylid en e-â-D-fu cop yr a n osyl]oxy]h exa d eca n oic Acid
1,2′′′-La cton e (12). 2,4,6-Trichlorobenzoyl chloride (0.012
mmol) was added to a mixture of hydroxy acid 11 (15 mg, 0.012
mmol) and Et3N in benzene (5 mL), and the solution was
stirred under N2 for 2 h at rt. The resulting mixture was
filtered through a short pad of Celite, diluted with toluene (5
mL), and added to a refluxing solution of DMAP (0.3 mmol)
in toluene (10 mL) over a period of 6 h. The reaction was
washed with cold 1 M HCl (1 × 5 mL), a saturated solution of
NaHCO3 (2 × 5 mL), and brine (1 × 5 mL) and dried over
Na2SO4. The organic phase was concentrated and purified by
chromatography on silica gel with 2% EtOAc in hexanes to
give 9 mg (60%) of compound 12 as a syrup: [R]D -28 (c )
0.80, CH2Cl2); IR (CH2Cl2 solution) 1738 cm-1 1H NMR
;
(CHCl3) δ 0.86 (t, 3 H, J ) 7.1), 1.13-1.90 (m, 33H), 2.30-
2.58 (m, 2H), 3.50-4.40 (m, 15H), 4.42 (d, J ) 10.8 Hz, 1H),
4.59 (d, J ) 10.8 Hz, 1H); 4.62 (d, J ) 10.5 Hz, 1H); 4.80-
5.00 (m, 8H), 5.47 (m, 1H), 5.50 (dd, J ) 7.5, 8.5, 1H) [Qui-2],
7.10-8.40 (m, 25H); 13C NMR (C5D5N) δ 14.2, 17.7, 18.3, 22.4,
22.5, 24.8, 25.3, 25.7, 26.5, 27.8, 29.3, 29.7, 29.9, 29.5, 30.1,
31.9, 34.5, 34.9, 37.4, 67.6, 69.5, 71.9, 73.2, 74.4, 74.8, 74.9,
75.2, 75.3, 76.2, 76.9, 77.4, 77.9, 80.3, 80.4, 83.1, 85.0, 85.2,
100.0, 101.7, 101.9, 109.6, 127.2, 127.5, 128.2, 128.5, 138.9,
178.1; negative-ion HRFAB-MS m/z 1197.6517 [M - H]- (calcd
for C72H93O15 m/z 1197.6514).
Ack n ow led gm en t . This work was supported by
the National Institutes of Health (GM 46057). The
National Council of Science and Technology of Mexico
(CONACyT) is thanked for funding the sabbatical visit
of M.B.A. to the University of California (010141).
R.P.-M. acknowledges financial support from Direccion
General de Asuntos del Personal Academico, UNAM
(IN200902-2). We thank Mariela Colo´n and Chambers
Hughes for NMR determination.
(11S)-Hyd r oxyh exa d eca n oic Acid 11-O-â-D-Qu in ovo-
p yr a n osyl-(1f2)-O-â-D-glu cop yr a n osyl-(1f2)-â-D-fu cop y-
r a n osid e 1,2′′′-La cton e (Tr icolor in F , 1). To a solution of
12 (15 mg, 0.012 mmol) in 0.5 mL of MeOH was added 0.5
mL of 10% HCl in MeOH and 8 mg of Pd(OH)2-C 10%
(Pearlman’s catalyst). The reaction mixture was evacuated,
Su p p or tin g In for m a tion Ava ila ble: NMR spectra of 7,
8, 10, 11, 12, 1, and authentic tricolorin F. This material is
available free of charge via the Internet at http://pubs.acs.org.
J O030244C
4570 J . Org. Chem., Vol. 69, No. 14, 2004