Total synthesis of tricolorin A

Article abstract of DOI:10.1021/jo9711450

Tricolorin A (1), a structurally amazing resin glycoside with promising bioactivities from Ipomoea tricolor cav. (convolvulaceae), was synthesized in a total of 45 steps, with the longest linear sequence of 20 steps and overall yield of 0.65% from D-mannitol. The AB disscharide 19-membered lactone 2 was constructured by a regioselective macrolactonization using Corey-Nicolaou protocol. The macrolactone tetrasaccharide 33 was realized either by 'one- pot two-step' glycosylation procedure or by a stepwise assembly employing the 'armed-disarmed' glycosylation strategy.

Full text of DOI:10.1021/jo9711450

8400
J . Org. Chem. 1997, 62, 8400-8405
Tota l Syn th esis of Tr icolor in A
Shou-Fu Lu, QinQin O’yang, Zhong-Wu Guo, Biao Yu,* and Yong-Zheng Hui*
State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China
Received J une 24, 1997X
Tricolorin A (1), a structurally amazing resin glycoside with promising bioactivities from Ipomoea
tricolor cav. (convolvulaceae), was synthesized in a total of 45 steps, with the longest linear sequence
of 20 steps and overall yield of 0.65% from D-mannitol. The AB disaccharide 19-membered lactone
2 was constructured by a regioselective macrolactonization using Corey-Nicolaou protocol. The
macrolactone tetrasaccharide 33 was realized either by “one-pot two-step” glycosylation procedure
or by a stepwise assembly employing the “armed-disarmed” glycosylation strategy.
Sch em e 1. Retr osyn th esis of Tr icolor in A
In tr od u ction
Tricolorin A (1), a member of the resin glycoside
family,1 was isolated by Pereda-Miranda in 1993 from
Ipomoea tricolor cav. (convolvulaceae), a plant used in
Mexican traditional agriculture as a weed controller.2
Bioassays showed that tricolorin A not only took major
responsibility for the weed growth inhibition of the plant
but also possessed significant cytotoxic activity against
cultured P-388 and human breast cancer cells (ED50 2.2
µg/mL).2a What attracted us more was the beauty of the
structure of tricolorin A that, bearing a disaccharide
containing 19-membered macrolactone, was in a perfect
balance of hydrophobicity and hydrophilicity. Therefore,
we made an effort directed toward the total synthesis of
this interesting molecule. While our synthesis was
underway, Schmidt first accomplished a total synthesis
of another molecule of the resin glycoside family
(calonyctin A).3 Recently, Heathcock reported a com-
munication on the synthesis of a macrolactone disaccha-
ride subunit (2) of tricolorin A.4 Coincidentally, we
employed a similar strategy to assembly this subunit (2)
in our total synthesis. Herein, we wish to describe the
total synthesis of tricolorin A. The synthesis was high-
lighted by a regioselective macrolactonization of a 1-(hy-
droxycarbonyl)pentadec-10(s)-yl disaccharide to build the
macrolactone disaccharide 2 and a “one-pot two-step”
assembly of two monosaccharide donors (3 and 4) to 2.5
(Scheme 1).
* To whom correspondence should be addressed. Phone: (86) 21-
64163300-1407. Fax: (86) 21-64166128. E-mail: byusioc@fudan.ac.cn.
X Abstract published in Advance ACS Abstracts, November 15, 1997.
(1) Lu, S.-F.; O’yang, Q.; Guo, Z.-W.; Hui, Y.-Z. Youji Huaxue 1997,
4, 1.
(2) (a) Pereda-Miranda, R.; Mata, R.; Anaya, A. L.; Wickramaratne,
D. B. M.; Pezzuto, J . M.; Kinghorn, A. D. J . Nat. Prod. 1993, 56, 571.
(b) Bah, M.; Pereda-Miranda, R. Tetrahedron 1996, 52, 13063.
(3) (a) J iang, Z.-H.; Geyer, A.; Schmidt, R. R. Angew. Chem., Int.
Ed. Engl. 1995, 34, 2520. (b) J iang, Z.-H.; Schmidt, R. R. Liebigs Ann.
Chem. 1994, 645. (c) J iang, Z.-H. Dissertation, Universitat Konstan,
1995.
(4) Larson, D. P.; Heathcock, C. H. J . Org. Chem. 1996, 61, 5208.
(5) For all efforts so far on “one-pot” glycosylation, see: (a) Grice,
P.; Ley, S. V.; Pietruszka, J .; Osborn, H. M. I.; Priepke, H. W. M.;
Warriner, S. L. Chem. Eur. J . 1997, 3, 431. (b) Cheng, M.-K.; Douglas,
N. L.; Hinzen, B.; Ley, S. V.; Pannecoucke, X. Synlett 1997, 257. (c)
Ley, S. V.; Priepke, H. W. M. Angew. Chem., Int. Ed. Engl. 1994, 33,
2292. Ley, S. V.; Priepke, H. W. M. Angew. Chem. 1994, 106, 2412.
(d) Grice, P.; Ley, S. V.; Pietruszka, J .; Prieke, H. W. M.; Walther, E.
P. E. Synlett 1995, 781. (e) Yamada, H.; Harada, T.; Takahashi, T. J .
Am. Chem. Soc. 1994, 116, 7919. (f) Chenault, H. K.; Castro, A.
Tetrahedron Lett. 1994, 35, 9145. (g) Yamada, H.; Harada, T.;
Miyazaki, H.; Takahashi, T. Tetrahedron Lett. 1994, 35, 3979. (h)
Raghavan, S.; Kahne, D. J . Am. Chem. Soc. 1993, 115, 1580.
Resu lts a n d Discu ssion
First, four monosaccharide building blocks (7, 10, 3,
and 4) were prepared as shown in Scheme 2, which were
all glycosyl donors either with a neighboring participation
group (7, 10, and 3) or with high anomeric effect (3 and
4) to warrant the highly selective â-glycosidation (for 7
and 10) or R-glycosidation (for 3 and 4). 2,3,4-Tri-O-
acetyl-R-D-fucopyranosyl trichloroacetimidate (7) was
prepared from peracetylated D-fucose (5) by selective
deacetylation at the anomeric position6 and trichloro-
acetonitrile addition, and 5 was readily obtained from
D-galactose in four steps by Lerner’s procedure.7 Ethyl
4,6-O-benzylidene-2,3-di-O-acetyl-1-thio-â-D-glucopyrano-
side (10) was synthesized from ethyl 1-thio-â-D-gluco-
(6) Fiandor, J .; Garc´ıa-Lo´pez, M. T.; De Las Heras, F. G.; Me´ndes-
Castrillo´n, P. P. Synthesis 1985, 1121.
(7) Lerner, L. M. Carbohydr. Res. 1993, 241, 291.
S0022-3263(97)01145-6 CCC: $14.00 © 1997 American Chemical Society

Total Synthesis of Tricolorin A
J . Org. Chem., Vol. 62, No. 24, 1997 8401
Sch em e 2. P r ep a r a tion of Mon osa cch a r id e
Bu ild in g Block s 7, 10, 3, a n d 4a
Sch em e 3. P r ep a r a tion of Meth yl
11(S)-J a la p in ola tea
a
Reagents and Conditions: (i) NH3, MeOH-THF (3:7), 0 °C, 3
a
Reagents and conditions: (i) t-BuLi/pentane (1.5 mol/mL), -30
h, 50%; (ii) CNCCl3, DBU, CH2Cl2, rt, overnight, 79%; (iii) NaOMe
(cat.), MeOH, 0 °C, 2 h, 90%; (iv) PhCH(OMe)2, p-TsOH, 50 °C,
4.5 h, 61%; (v) Ac2O, Py, overnight, 84%; (vi) Bu2SnO, toluene,
reflux, 1 h, then PMBCl, CsF, Bu4NI, DMF, rt, 33 h, 79%; (vii)
2(S)-methylbutyric anhydride (2.0 equiv), DMAP, Py, rt, 27 h, 70%;
(viii) CAN (2.0 equiv), CH3CN-H2O (9:1), 25 min, 97%.
°C to rt, 1 h, 70%; (ii) LiAlH4, THF, reflux, 12 h, 95%; (iii) Ac2O,
Py, rt, 2 h, 95%; (iv) KMnO4, benzene-H2O-HOAc (4:4:1), Bu4NI,
rt, overnight, 91%; (v) Br2, HgO, CCl4, reflux, 5 h, 83%; (vi) p-TsOH
(cat.), CH3OH, reflux, 1.5 h, 92%; (vii) TBDMSCl, imidazole, rt, 3
h, 97%; (viii) Mg, THF, reflux, 2 h, then CuI (cat.), 15 (1.0 equiv),
-78 °C to rt, 2.5 h, 66%; (ix) Ac2O, Py, rt, overnight, 91%; (x) J ones
reagent, acetone, rt, 1.5 h, 89%; (xi) BF3‚OEt2 (3.0 equiv), MeOH,
40 °C, 4 h, 97%.
pyranoside (8), which was readily available from D-
glucose,8 by benzylidenization and acetylation. Ethyl
1-thio-R-L-rhamnopyranoside (11), readily prepared from
L-rhamnose by a known procedure in three steps,5c was
selectively protected at 3-OH with a p-methoxybenzyl
(PMB) group by sequential treatment with Bu2SnO,
PMBCl, CsF, and Bu4NI in DMF to give ethyl 3-O-PMB-
1-thio-R-L-rhamnopyranoside (12),9 which was further
converted to ethyl 2,4-di-O-Mba(2s)-3-O-PMB-1-thio-R-
L-rhamnopyranoside (13) by treatment with commercially
available 2(s)-methylbutyric anhydride (from Aldrich) in
pyridine in the presence of DMAP. Removal of the 3-O-
PMB group with cerium(IV) ammonium nitrate (CAN)9
afforded ethyl 2,4-di-O-Mba(2s)-1-thio-R-L-rhamnopyra-
noside (3). Alternatively, 11 was benzylated to provide
the ethyl 2,3,4-tri-O-benzyl-1-thio-R-L-rhamnopyranoside
(4).5c
(Scheme 3). 2(S)-Hydroxyheptanyl tosylate (14), readily
obtained from D-mannitol in seven steps in a yield of 6.7%
according to Barry’s procedure,11 was treated with t-BuLi
to afford the 1,2(S)-epoxyheptane (15) (overall yield of
4.7% from D-mannitol).12 On the other hand, transfor-
mation of undecylenic acid to ω-bromononanyl (tert-butyl
dimethyl) silyl ether (21) was easily realized in six steps
(overall 61% yield): reduction with LiAlH4, acetylation,
oxidative cleavage of the double bond by KMnO4,13
Hunsdieck decarboxylic bromination,14 deacetylation, and
protection of 1-OH with TBDMS. Conversion of 21 into
the Grignard reagent followed by treatment with epoxide
15 in the presence of catalytic CuI conveniently afforded
1-(tert-butyldimethylsiloxy)-11(S)-hexadecanol (22) in 66%
yield. Protection of the 11(S)-hydroxyl of 22 with acetyl,
followed by J ones oxidation, provided 11(S)-acetoxy-1-
hexadecanoic acid (24), which was transferred to methyl
11(S)-jalapinolate (25) in one step by treatment with
BF3‚OEt2 in MeOH.
Secondly, methyl 11(S)-jalapinolate [methyl 11(S)-
hydroxyhexadecanoyl ester (25)]10 was prepared employ-
ing a chiral pool approach starting from D-(+)-mannitol
(8) Erbing, B.; Lindberg, B. Acta Chem. Scand. B 1976, 30, 611.
(9) The procedure was according to the preparation of methyl
3-O-(4-methoxybenzyl)-1-thio-R-L-rhamnopyranoside: Kovac, P. Car-
bohydr. Res. 1993, 245, 219.
(10) For previous efforts on the syntheses of (11S)-jalapinoic acid,
see: (a) Nodo, N.; Ono, M.; Miyahara, K.; Kawasaki, T.; Okabe, M.
Tetrahedron 1987, 43, 1889. (b) Shibaya, H.; Kitagawa, I. Chem.
Pharm. Bull. 1989, 37, 260. (c) Ono, M.; Kubo, K.; Miyahara, K.;
Kawasaki, T. Chem. Pharm. Bull. 1989, 37, 241.
(11) (a) Tipson, R. S.; Cohen, A. Carbohydr. Res. 1968, 7, 232. (b)
J ackson, D. Y. Synth. Commun. 1988, 18, 337. (c) Barry, J .; Kagan,
H. B. Synthesis 1981, 453.
(12) Schmidt, U.; Talbiersky, J .; Bartkowiak, F.; Wild, J . Angew.
Chem., Int. Ed. Engl. 1980, 19, 198.
(13) Krapcho, A. P.; Larson, J . R.; Eldridge, J . M. J . Org. Chem.
1977, 42, 3749.
(14) Hammoud, A.; Descoins, C. Bull. Soc. Chim. Fr. 1978, 299.

8402 J . Org. Chem., Vol. 62, No. 24, 1997
Lu et al.
Sch em e 4. P r ep a r a tion of AB Disa cch a r id e
Ma cr ola cton e Accep tor 2a
Sch em e 5. Syn th esis of Tr icolor in A by a
Step w ise or “On e-P ot” P r oced u r ea
a
Reagents and conditions: (i) 7 (1.0 equiv), 25 (0.9 equiv),
BF3‚OEt2 (1.2 equiv), CH2Cl2, -15 °C, 1 h, 66%; (ii) 1% NaOMe,
MeOH, -15 °C, 25 min; (iii) Me2C(OMe)2, p-TsOH, acetone,
overnight, 82% (two steps); (iv) 10 (1.6 equiv), NIS (3.0 equiv),
AgOTf (1.0 equiv), 4 Å MS, CH2Cl2, -15 °C, 0.5 h, 76%; (v) 3%
KOH, MeOH-H2O (9:1), reflux, 24 h, 91%; (vi) (PyS)2, Ph3P,
toluene, reflux, 7 days, 69% for 2, 11% for 31.
a
Reagents and conditions: (i) IDCP (2.3 equiv), 4 Å MS, CH2Cl2,
rt, 0.5 h, 98%; (ii) NIS (4.5 equiv), AgOTf (0.5 equiv), 4 Å MS,
CH2Cl2, rt, 1 h, 86%; (iii) (a) DDQ (3.0 equiv), CH3CN-H2O (9:1),
reflux, 4 h; (b) H2 (6 MPa), 10% Pd-C, 60 °C, 7 h, 70% (two steps);
(iv) 3 (1.2 equiv), 4 (1.0 equiv), NIS (1.4 equiv), TfOH (cat.), 4 Å
MS, Et2O-DCE (1:1), -15 °C, 15 min; (v) 2 (1.6 equiv), NIS (1.4
equiv), TfOH (cat.), 4 Å MS, rt, 1 h, 43% (based on 2).
With methyl 11(S)-jalapinolate (25) and monosaccha-
ride donors 7 and 10 in hand, we sought to construct the
macrolactone disaccharide 2 (Scheme 4). Alcohol 25 was
readily glycosylated by imidate 7 using Schmidt’s pro-
cedure15 to afford 26, which was sequentially subjected
to deacetylation and isopropylidenization to give rise to
28 with only 2′-OH free. Treatment of alcohol 28 with
thioglycoside donor 10 in the presence of NIS and AgOTf
in CH2Cl2 at -15 °C led to the disaccharide 29 in 76%
yield, which was saponified with 3% KOH in MeOH-
H2O (9:1) to provide the acid 30 with 2′′,3′′-OH free.
Regioselective macrolactonization of 30 by Corey-Nico-
laou’s protocol16 gave the desired 3′′-OH macrolactonized
product 2 in 69% yield, together with 11% of the 2′′-OH
macrolactonized product 31.
Finally, the macrolactone tetrasaccharide 33 was as-
sembled by a facile “one-pot, two-step” glycosylation of 2
with thioglycoside donors 3 and 4 under NIS/TfOH (cat.)
in 43% yield (based on consumed 2)5 (Scheme 5). Alter-
natively, 33 was also constructed stepwise. Disaccharide
synthon 32, the intermediate in the above “one-pot”
protocol, was efficiently synthesized by the reaction of
thioglycosides 3 and 4 involving the well-known “armed-
disarmed” glycosidation approach17 in the presence of
IDCP (iodium di-sym-collidine perchlorate).18 Glycosy-
lation of macrolactone disaccharide 2 by disaccharide
donor 32 in the presence of promoter (NIS/AgOTf)19
afforded the important precursor (33) of tricolorin A in
good yield (86%). Final deprotection of the 3′,4′-O-
isopropylidene and 4′′,6′′-O-benzylidene of 33 by DDQ20
followed by removal of the benzyl groups by hydrogena-
tion provided tricolorin A in 70.4% yield. The physical
data were in identical to those reported.2
In conclusion, we have achieved the first total synthesis
of tricolorin A in a total 45 steps, with the longest linear
sequence of 20 steps and overall yield of 0.65% from
D-(+)-mannitol. The synthetic route is highlighted by the
regioselective macrolactonization of a disaccharide bear-
ing 19-membered ring and the “one-pot” glycosidation for
construction of a macrolactone tetrasaccharide.
Exp er im en ta l Section
Gen er a l Meth od s. Solvents were purified in the usual
way, and melting points were uncorrected. TLC was per-
(18) (a) Lemieux, R. U.; Morgan, A. R. Can. J . Chem. 1965, 43, 2190.
(b) Veeneman, G. H.; van Boom, J . H. Tetrahedron Lett. 1990, 31, 275.
(c) Zuurmond, H. M.; van der Meer, P. H.; van der Klein, P. A. M.; van
der Marel, G. A.; van Boom, J . H. J . Carbohydr. Chem. 1993, 12, 1091.
(d) Zegelar-J arsveld, K.; van der Marel, G. A.; van Boom, J . H.
Tetrahedron 1992, 48, 10133.
(19) (a) Konradsson, P.; Udodong, U. E.; Fraser-Reid, B. Tetrahedron
Lett. 1990, 31, 4313. (b) Takeo, K.; Nagayoshi, K.; Nishimura, K.;
Kitamura, S. J . Carbohydr. Chem. 1994, 13, 1159.
(15) Schmidt, R. R.; Michel, J . Angew. Chem., Int. Ed. Engl. 1980,
19, 731.
(16) Corey, E. J .; Nicolaou, K. C. J . Am. Chem. Soc. 1974, 96, 5614.
(17) Mootoo, D. R.; Konradsson, P.; Udodong, U.; Fraser-Reid, B. J .
Am. Chem. Soc. 1988, 110, 5583.
(20) For removal of acetal or ketal by DDQ, see: (a) Fenandez, J .
M. G.; Mellet, C. D.; Marin, A. M.; Fuentes, J . Carbohydr. Res. 1995,
274, 263. (b) Oku, A.; Kinugasa, M.; Kamada, T. Chem. Lett. 1993,
165. (c) Tanemura, K.; Suzuki, T.; Horaguchi, T. J . Chem. Soc., Chem.
Commun. 1992, 979.

Total Synthesis of Tricolorin A
J . Org. Chem., Vol. 62, No. 24, 1997 8403
formed on precoated plates of silica gel HF254 (0.5 mm,
Qingdao, China) and detected by 10% concentrated sulfuric
acid in methanol. Flash column chromatography was carried
out on silica gel H (400 mesh, Qingdao, China). Coupling
constants (J ) are reported in Hz.
2,3,4-Tr i-O-a cetyl-r-D-fu cop yr a n osyl Tr ich lor oa cetim i-
d a te (7). 5 (4.680 g, 14.08 mmol) was dissolved in a solution
of NH3 in MeOH/THF (200 mL, 3/7 v/v) (prepared by bubbling
NH3 into MeOH-THF until the system was not exothermic).
The mixture was stirred for 3 h at 0 °C and then concentrated.
The residue was purified by flash chromatography on a silica
gel column (petroleum ether-EtOAc, 7:3, then 7:3:1% MeOH)
to afford a white solid 6 (1.922 g, 50%, 5 (652 mg, 14%) was
recovered).
syrup 13 (4.292 g, 69.7%): [R]18 -34.30 (c 3.65, CHCl3); IR
D
(neat) 1741, 1613 cm-1; 1H NMR (300 MHz, CDCl3) 7.15, 6.81
(4H, m), 5.42 (1H, dd, J ) 1.5, 2.9), 5.19 (1H, s), 5.06 (1H, t, J
) 9.7), 4.52 (1H, d, J ) 11.2), 4.30 (1H, d, J ) 11.2), 4.11 (1H,
dq, J ) 9.8, 6.2), 3.77 (3H, s), 3.76 (1H, dd, J ) 3.2, 8.3), 2.62
(2H, m), 2.48 (1H, m), 2.32 (1H, m), 1.67, 1.45 (2H each, m),
1.28 (3H, t, J ) 7.2), 1.18 (3H, d, J ) 6.4), 1.15 (3H, d, J )
7.2), 1.11 (3H, d, J ) 6.9), 0.88 (3H, t, J ) 7.5), 0.87 (3H, t, J
) 7.3); FABMS m/z 496 (M+), 495 (M+ - 1), 435 (M+ - EtS).
Eth yl 2,4-Di-O-[2(S)-m eth ylbu tyr yl]-1-th io-r-L-r h a m -
n op yr a n osid e (3). To a solution of 13 (1.027 g, 2.07 mmol)
in CH3CN-H2O (30 mL, 10:1) was added cerium(IV) am-
monium nitrate (2.280 g, 4.17 mmol) at rt. The mixture was
stirred for 25 min and then quenched with saturated aqueous
NaCO3 solution and diluted with EtOAc. The mixture was
washed with brine. The organic layer was separated, dried
over Na2SO4, and concentrated. Flash chromatography on a
silica gel column (petroleum-EtOAc, 9:1, then 4:1) gave rise
to a colorless syrup 3 (641 mg, 97.5% based on reacted 13,
To a solution of 6 (439 mg, 1.3 mmol) in CH2Cl2 (5 mL) were
added CNCCl3 (2.5 mL, 24.6 mmol) and DBU (0.2 mL, 1.3
mmol). The mixture was stirred at rt overnight under argon
and then concentrated and flash chromatographed on a silica
gel column (petroleum ether-EtOAc, 7:3) to give 7 (480 mg,
79%) as a white amorphous solid: [R]16D +132.8 (c 0.30, CHCl3)
159 mg 13 was recovered): [R]16 -62.13 (c 21.9, CHCl3); IR
D
(lit.3c [R]16 +106.4 (c 3.2, CHCl3)); IR (KBr) 3333, 1746, 1677
(neat) 3484, 1741 cm-1; 1H NMR (300 MHz, CDCl3) 5.24 (1H,
d, J ) 1.3), 5.15 (1H, dd, J ) 1.5, 3.5), 4.88 (1H, t, J ) 9.3),
4.19 (1H, dq, J ) 9.9, 6.3), 3.89 (1H, ddd, J ) 3.5, 9.8, 8.3),
2.64 (2H, m), 2.54-2.41 (2H, m), 2.17 (1H, d, J ) 8.2), 1.78-
1.64, 1.60-1.46 (2H each, m), 1.30 (3H, t, J ) 7.4), 1.23 (3H,
d, J ) 6.4), 1.20 (3H, d, J ) 7.2), 1.18 (3H, d, J ) 6.9), 0.94
D
1
cm-1; H NMR (300 MHz, CDCl3) 8.61 (1H, s), 6.55 (1H, d, J
) 3.4), 5.45-5.39 (2H, m), 5.34 (1H, dd, J ) 10.4), 4.37 (1H,
m), 2.19, 2.02 and 2.01 (3H each, s each), 1.19 (3H, d, J )
6.5).
Eth yl 4,6-O-Ben zylid en e-2,3-d i-O-a cetyl-1-th io-â-D-glu -
cop yr a n osid e (10). A mixture of 9 (1.026 g, 4.58 mmol),
PhCH(OMe)2 (6 mL, 39 mmol), and p-TsOH (0.05 g) in DMF
(50 mL) (PH 3.0) was stirred at 50 °C for 4.5 h and then was
neutralized by addition of anhydrous K2CO3. After removal
of DMF and PhCH(OMe)2 under vacuum, the residue was
diluted with EtOAc (50 mL), filtered through a short column
of silica gel, and concentrated. Flash chromatography on a
silica gel column (CH2Cl2-CH3OH, 9:1) gave rise to ethyl 4,6-
O-benzylidene-1-thio-â-D-glucopyranoside (0.897 g, 61%) as a
white needle.
(3H, t, J ) 7.4), 0.94 (3H, t, J ) 7.4); EIMS m/z 315 (M+
-
EtS, 63.1). Anal. Calcd for C18H32O6S: C, 57.42; H, 8.57.
Found: C, 57.38; H, 8.74.
1,2(S)-Ep oxyh ep ta n e (15). To a solution of 14 (5.1 g, 17.8
mmol) in Et2O (50 mL) was added dropwise tBuLi/pentane (1.5
M, 14 mL, 21 mmol, purchased from J anssen Chemica) at -30
°C, then the mixture was warmed to 20 °C and stirred for 1 h.
After the mixture was cooled to -20 °C, a saturated aqueous
solution of NH4Cl (2 mL) was added to quench the reaction.
The mixture was extracted with Et2O (70 mL × 3), washed
with brine, dried over Na2SO4, and concentrated. Flash
chromatography on a silica gel column (pentane-Et2O, 100:
3) furnished a yellow oil 15 (1.429g, 70%): [R]20D -9.46 (c 0.43,
CHCl3) (lit.12 [R]21D -12.3 (c 6.0, dioxane); 1H NMR (300 MHz,
CDCl3) 2.87 (1H, m), 2.70 (1H, pseudo-t, J ) 4.8, 4.1), 2.43
(1H, dd, J ) 2.5, 5.0), 1.50 (4H, m), 1.28 (4H, m), 0.86 (3H, t,
J ) 7.0); EIMS m/z 113 (M+ - 1, 0.3), 71 (M+ - C2H3O, 100.0),
43 (M+ - C5H11, 31.8).
The above product (265 mg, 0.85 mmol) was dissolved in
Py (15 mL) and Ac2O (2 mL). The solution was stirred at rt
overnight. After removal of Py and Ac2O under vacuum, the
residue was purified by chromatography on a silica gel column
(petroleum ether-EtOAc, 80:7) to afford 10 (284 mg, 84.4%)
as a white needle: mp 139-141 °C; [R]24 -72.45 (c 0.62,
D
CHCl3); IR (KBr) 1753, 1731 cm-1; 1H NMR (300 MHz, CDCl3)
7.45-7.35 (5H, m), 5.51 (1H, s), 5.35 (1H, t, J ) 9.13), 5.05
(1H, dd, J ) 10.1, 9.3), 4.59 (1H, d, J ) 10.1), 4.38 (1H, dd, J
) 10.5, 4.9), 3.79 (1H, t, J ) 10.1), 3.70 (1H, t, J ) 9.5), 3.57
(1H, m), 2.72 (2H, m), 2.08, 2.05 (3H each, s each), 1.27 (3H,
t, J ) 7.52); EIMS m/z 335 (M+ - EtS, 1.6%). Anal. Calcd
for C19H24O5S: C, 57.56; H, 6.10; S, 8.09. Found: C, 57.26;
H, 5.84; S, 8.16.
ω-Br om on on a n yl Dim eth yl-ter t-bu tylsilyl Eth er (21).
A mixture of 20 (28 g, 118 mmol), TBDMSCl (23 g, 152 mmol),
imidazole (12 g, 176 mmol), and catalytic DMAP in CH2Cl2
(300 mL) was stirred for 3 h at rt under nitrogen. The reaction
mixture was filtered and concentrated. Flash chromtography
on a silica gel column (petroleum-EtOAc, 9:1) gave rise to 21
(39g, 97%) as a colorless oil: 1H NMR (300 MHz, CDCl3) 3.59
(2H, t, J ) 6.6), 3.40 (2H, t, J ) 6.9), 1.84 (2H, m), 1.52-1.29
Eth yl 2,4-Di-O-[2(S)-m eth ylbu tyr yl]-3-O-(p-m eth oxy-
ben zyl)-1-th io-r-L-r h a m n op yr a n osid e (13). A mixture of
11 (3.256 g, 15.7 mmol) and Bu2SnO (4.873 g, 19.6 mmol) in
toluene (100 mL) was refluxed for 1 h in a Soxhlet apparatus
with a thimble containing 4 Å molecular sieves. Then the
solution was concentrated. The residue was suspended in
DMF (75 ML), and finely powdered CsF (4.8 g, 31.7 mmol),
Bu4NI (14.5 g, 19 mmol), and PMBCl (5.7 mL, 3.9 mmol) were
added. After being stirred at rt for 33 h, the mixture was
diluted with Et2O (300 mL) and washed with H2O (300 mL ×
3). The separated water phase was extracted with Et2O (100
mL × 2). The combined organic phase was washed with ice
water, dried over Na2SO4, and then filtered through a short
column of silica gel (containing a thin layer of active charcoal).
The eluent was concentrated to a residue, which was purified
by flash chromatography on a silica gel column (CH2Cl2-CH3-
OH, 95:2) to afford a colorless syrup 12 (4.068 g, 79%), which
was directly used in the next step.
A mixture of 12 (4.068 g, 12.4 mmol), 2(S)-methylbutyric
anhydride (5 mL, 25 mmol, purchased from Aldrich), and
catalytic DMAP in Py (30 mL) was stirred for 27 h under Argon
at rt. After the solvent was removed under reduced pressure,
the residue was diluted with EtOAc, washed with aqueous
NaHCO3 and brine, and then dried with anhydrous Na2SO4
and concentrated. Flash chromatography on a silica gel
column (petroleum ether-EtOAc, 100:3) afforded a colorless
(12H, m); EIMS m/z 339 (M+ - 1, 6). Anal. Calcd for C15H33
-
BrOSi, C, 53.39; H, 9.86; Br, 23.68. Found: C, 53.42; H, 9.68;
Br, 23.70.
1-(ter t-Bu tyld im eth ylsiloxy)-11(S)-h exa d eca n ol (22).
To flame-dried three-neck round-bottom flask (1 L) was added
a mixture of magnesium scrubbers (300 mg), catalytic I2, and
a 1 mL solution of 21 in THF (4g/20 mL, 11.9 mmol). The
mixture was heated to start the reaction, and then the
remaining solution of 21 in THF was added into the flask
dropwise. After being refluxed for 2 h, the reaction system
was cooled to -78 °C and catalytic CuI was added. The
mixture was stirred for 15 min and then was added to a
solution of 15 in THF (1.118 g/15 mL, 3.31 mmol) by drop
funnel followed by slow warming to rt for 1.5 h. The reaction
proceeded for an additional 1 h at rt and then was quenched
with a saturated aqueous solution of NH4Cl (4 mL) at -78
°C. The mixture was dried over Na2SO4, filtered, and concen-
trated. Flash chromatography on a silica gel column (petro-
leum-EtOAc, 80:5) gave rise to 22 (2.411 g, 66.0%) as a white
waxy solid: mp 35-38 °C; [R]21D +0.28 (c 4.0, CHCl3); IR (KBr)
1
3400 cm-1; H NMR (600 MHz, CDCl3) 3.55 (3H, t, J ) 6.6),
1.56 (2H, m), 1.38 (4H, m), 1.25 (20H, m), 0.85 (6H, s), 0.85
(3H, t, J ) 6.9), 0.00 (6H, s); EIMS m/z 355 (M+ - OH, 1.0),

8404 J . Org. Chem., Vol. 62, No. 24, 1997
Lu et al.
301 (M+ - C5H11, 6.2). Anal. Calcd for C22H48O2Si: C, 70.90;
H, 12.98. Found: C, 70.82; H, 13.26.
TsOH (15 mg) was added. The reaction proceeded overnight
at rt under argon, neutralized with powdered K2CO3, and then
filtered through a short column of silica gel. Flash chroma-
tography on a silica gel column (petroleum ether-EtOAc, 7:1)
furnished 28 (154 mg, 82%) as a oil: 1H NMR (300 MHz,
CDCl3) 4.16 (1H, d, J ) 8.3), 4.04-4.00 (2H, m), 3.84 (1H, m),
3.67 (3H, s), 3.60 (1H, t, J ) 5.7), 3.51 (1H, m), 2.30 (2H, t, J
) 7.5), 1.54, 1.36 (3H each, s each), 1.40 (3H, d, J ) 6.5), 1.65-
1.27 (24H, m), 0.89 (3H, t, J ) 7.1).
A mixture of 28 (642 mg, 1.4 mmol), 10 (1.1 g, 2.8 mmol),
and 4 Å MS (2 g) in CH2Cl2 (20 mL) was stirred at rt for 15
min under nitrogen. The reaction system was then cooled to
-15 °C, and NIS (1.1 g, 5.0 mmol) was added immediately
followed by a solution of AgOTf (300 mg, 1.4 mmol) in toluene
(5 mL). After the mixture was stirred for 0.5 h, Et3N (1 mL)
was added to quench the reaction. The mixture was filtered
through a short column of silica gel and diluted with CH2Cl2
(150 mL). The solution was washed with 10% aqueous
Na2S2O3 and ice water, dried over Na2SO4, and concentrated.
Flash chromatography on a silica gel column (petroleum
1-(ter t-Bu t yld im et h ylsiloxy)-11(S)-h exa d eca n yl a c-
eta te (23). A mixture of 22 (1.577 g, 4.2 mmol) and Ac2O (3
mL) in Py (15 mL) was stirred overnight at rt. After Py and
the remaining Ac2O were removed under vacuum, the residue
was purified by flash chromatography on a silica gel column
(petroleum ether-EtOAc, 100:0.6) to afford 23 (1.794 g, 90.5%)
as a colorless oil: [R]22D -1.02 (c 11.39, CHCl3); IR (film) 1740
1
cm-1; H NMR (300 MHz, CDCl3) 4.79 (1H, m), 3.52 (2H, t, J
) 6.6), 1.96 (3H, s), 1.43 (6H, m), 1.19 (20H, br), 0.82 (9H, s),
0.81 (3H, t, J ) 7.1), 0.3 (6H, s); EIMS m/z 415 (M+ + 1, 1.5),
343 (M+ - C5H11, 3.3). Anal. Calcd for C24H50O3Si: C, 69.50;
H, 12.15. Found: C, 69.30; H, 11.82.
11(S)-Acetoxy-1-h exa d eca n oic Acid (24). To a solution
of 23 (657 mg, 1.53 mmol) in acetone (15 mL) was added J ones
reagent (2.0 mL) by drop funnel at 0 °C. After the mixture
was stirred for 1.5 h at rt, a saturated aqueous solution of
NaHCO3 was added to quench the reaction. The mixture was
filtered, and the liquid portion was diluted with EtOAc (80
mL), washed successively with 10% aqueous citric acid and
brine, dried over Na2SO4, and concentrated. Flash chroma-
tography on a silica gel column (petroleum ether-EtOAc, 7:3)
gave rise to 24 (429 mg, 89.4%) as a colorless oil: [R]23D -0.79
ether-EtOAc, 7:1) afforded 29 (838 mg, 76.5%) as a yellow
1
syrup: [R]16 -21.02 (c 4.2, CHCl3); IR (neat) 1757 cm-1; H
D
NMR (600 MHz, CDCl3) 7.5-7.4 (5H, m), 5.50 (1H, s), 5.31
(1H, m), 5.01-4.96 (2H, m), 4.34 (1H, dd, J ) 5.0, 10.3), 4.12
(1H, d, J ) 8.0), 4.03 (1H, t, J ) 5.8), 3.95 (1H, dd, J ) 1.9,
5.7), 3.83-3.72 (3H, m), 3.66 (3H, s), 3.64-3.52 (3H, m), 2.30
(2H, t, J ) 7.5), 2.09, 2.05 (3H each, s each), 1.51, 1.33 (3H,
each, s each), 1.36 (3H, d, J ) 6.5), 1.7-1.2 (24H, m), 0.87
(3H, t); 13C NMR (150 MHz, CDCl3) 14.10, 16.59, 20.80, 20.84,
22.62, 24.71, 24.96, 25.15, 26.18, 26.31, 27.84, 27.96, 28.79,
28.97, 29.17, 29.31, 29.51, 29.69, 29.92, 31.96, 33.84, 34.10,
34.65, 51.40, 66.28, 68.49, 68.79, 72.07, 72.93, 76.43, 78.38,
79.24, 79.60, 80.49, 100.14, 100.70, 101.48, 109.66, 126.14,
128.22, 129.08, 136.93, 169.65, 170.15, 174.28; FABMS m/z
805 (M+ - 1). Anal. Calcd for C63H66O14: C, 64.00; H, 8.24.
Found: C, 63.82; H, 8.37.
(c 14.85, CHCl3); IR (film) 3050-2500, 1738, 1711 cm-1 1H
;
NMR (300 MHz, CDCl3) 4.86 (1H, m), 2.35 (2H, t, J ) 7.5),
2.04 (3H, s), 1.62 (2H, m), 1.49 (4H, m), 1.26 (22H, br), 0.88
(3H, t, J ) 6.6); EIMS m/z 315 (M+ + 1, 36.7. Anal. Calcd for
C18H34O4: C, 68.75; H, 10.90. Found: C, 68.84; H, 10.98.
Meth yl 11(S)-J a la p in ola te (25). A solution of 24 (367 mg
1.2 mmol) and BF3‚OEt2 (0.5 mL, 0.6 mmol) in absolute CH3-
OH (4 mL) was stirred at 40 °C for 4 h, and then Et3N was
added to quench the reaction. After removal of CH3OH and
Et3N, the residue was purified by flash chromatography on a
silica gel column (petroleum ether-EtOAc, 70:6) to give 25
(323 mg, 96.9%) as a colorless plate crystal: mp 48-49 °C;
[R]25 +1.37 (c 2.18, CHCl3) (lit.21 [R]D +1.2 (c 10.0 CHCl3));
1-(H yd r oxyca r b on yl)p en t a d ec-10(S)-yl
O-(4,6-O-
D
IR (KBr) 3334, 1746 cm-1
;
1H NMR (300 MHz, CDCl3) 3.66
Ben zylid en e-â-D-glu cop yr a n osyl)-(1f2)-3,4-O-isop r op y-
lid en e-â-D-fu cop yr a n osid e (30). A mixture of 29 (741 mg,
0.92 mmol) and KOH (500 mg, 9 mmol) in CH3OH-H2O (20
mL, 9:1, v/v) was refluxed for 10 h under argon. The mixture
was neutralized with IRC-85 Amberlite (weak H+), filtered,
and concentrated. Flash chromatography on a silica gel
column afforded 30 (597 mg, 91%) as an amorphous solid: IR
(KBr) 3430, 1710 cm-1; 1H NMR (300 MHz, CDCl3) 7.49-7.26
(5H, m), 5.53 (1H, s), 4.65 (1H, d, J ) 7.7), 4.31 (1H, dd, J )
4.8, 10.5), 4.28 (1H, d, J ) 8.1), 4.15 (1H, dd, J ) 5.5, 7.2),
4.01 (1H, dd, J ) 2.0, 5.4), 3.87-3.46 (5H, m), 2.31 (2H, t),
1.50, 1.34 (3H, each, s each), 1.37 (3H, d, J ) 6.6), 1.7-1.2
(24H, m), 0.88 (3H, t, J ) 7.0); FABMS m/z 437; 13C NMR (75.6
MHz, CDCl3) 179.0, 137.1, 129.2, 128.3, 126.4, 110.3, 104.1,
101.9, 100.3, 80.8, 80.7, 79.8, 78.6, 76.6, 76.0, 68.8, 68.5, 67.0,
34.5, 34.0, 33.7, 32.0, 30.0, 29.6, 29.4, 29.2, 29.0, 27.8, 26.2,
25.0, 24.7, 24.5, 22.6, 16.5, 14.2.
(3H, s), 3.57 (1H, m), 2.30 (2H, t, J ) 7.5), 1.61 (2H, m), 1.42-
1.28 (22H, m), 0.89 (3H, t, J ) 6.6); EIMS m/z 269 (M+ - OH,
57.2), 215 (M+ - C5H11, 12.0). Anal. Calcd for C17H34O3: C,
71.28; H, 11.96. Found: C, 71.11; H, 11.68.
1-(Met h oxyca r b on yl)p en t a d ec-10(S)-yl
2,3,4-Tr i-O-
a cetyl-â-D-fu cop yr a n osid e (26). A mixture of 7 (480 mg,
1.0 mmol), 25 (370 mg, 1.3 mmol), and 4 Å MS (0.8 g) in CH2-
Cl2 (4 mL) was stirred for 15 min at rt under argon and then
cooled to -30 °C, and a solution of BF3‚OEt2-CH2Cl2 (0.6 mL,
1:40, v/v) was added in one portion. After being warmed to 0
°C, the reaction was proceeded for another 1 h. Saturated
aqueous NaHCO3 was added to quench the reaction. The
mixture was dried over Na2SO4, filtered, and concentrated.
Chromatography on a silica gel column afforded a yellow oil
26 (334 mg, 65.7%, based on reacted 25, the acetyl transfer
product (109 mg) was also obtained): [R]18 +4.45 (c 2.56,
D
CHCl3); IR (film) 1755 cm-1; 1H NMR (300 MHz, CDCl3) 5.21
(1H, dd, J ) 2.9, 0.8), 5.16 (1H, dd, J ) 7.8, 10.4), 5.01 (1H,
dd, J ) 10.3, 3.4), 4.44 (1H, d, J ) 8.0), 3.77 (1H, dq, J ) 0.8,
6.5), 3.67 (3H, s), 3.53 (1H, m), 2.31 (2H, t, J ) 7.6), 2.17, 2.03,
1.98 (3H each, s each), 1.64-1.28 (24H, m), 1.20 (3H, d, J )
6.5), 0.88 (3H, t, J ) 7.0); 13C NMR (75 MHz, CDCl3) 14.19,
16.14, 16.23, 20.80, 22.63, 24.79, 24.98, 29.17, 29.28, 29.47,
29.62, 29.92, 31.91, 34.12, 34.77, 51.47, 68.94, 69.49, 70.47,
71.63, 81.33, 100.92, 169.40, 170.33, 170.85, 174.32; FABMS
559 (M+ + 1). Anal. Calcd for C29H50O11: C, 62.34; H, 9.02.
Found: C, 62.65; H, 9.09.
1-(Met h oxyca r b on yl)p en t a d ec-10(S)-yl O-(2,3-d i-O-
a cetyl-4,6-O-ben zylid en e-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 osid e (29). A mixture of
26 (229 mg, 0.41 mmol) in NaOMe-MeOH (1%, 5 mL) was
stirred at -15 °C for 25 min under argon. The solution,
neutralized with Dowex-50w (H+), was then filtered, concen-
trated, and dried under vacuum. The residue was dissolved
in acetone (5 mL) and Me2C(OMe)2 (1 mL, 8.21 mmol), and
1,3-(B)-La cton e of (S)-1-(Hyd r oxyca r bon yl)p en ta d ec-
10-yl O-(4,6-Ben zylid en e-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 osid e (2) a n d 1,2(B)-
Lacton e of (S)-1-(Hydr oxycar bon yl)pen tadec-10-yl O-(4,6-
B e n z y li d e n e -â-D-g lu c o p y r a n o s y l)-(1f2)-3,4-O -i s o -
p r op ylid en e-â-D-fu cop yr a n osid e (31). A solution of 30 (400
mg, 0.56 mmol), (PyS)2 (640 mg, 3.0 mmol), and Ph3P (750 mg,
3.0 mmol) in deoxygenated anhydrous toluene (15 mL) was
stirred for 5 h at rt under argon. The mixture was diluted
with deoxygenated anhydrous toluene (50 mL) and then was
added dropwise to the refluxing dry deoxygenated toluene (700
mL) over 10 h. The solution was refluxed under argon for 7
days. After removal of toluene, the residue was chromato-
graphed on a silica gel column (petroleum-EtOAc, 8:2) to afford
2 (270 mg, 69%) as colorless needles together with 31 (45 mg,
11%) as a white amorphous solid. 2: mp 209-211 °C; [R]19
D
-59.09 (c 0.07, CHCl3); IR (KBr) 3484, 1742 cm-1; H NMR
1
(300 MHz, CDCl3) 7.45-7.35 (5H, m), 5.52 (1H, s), 5.22 (1H,
t, J ) 8.8), 5.06 (1H, d, J ) 7.4) 4.30-4.23 (2H, m), 4.16 (1H,
t, J ) 6.0), 3.97-3.73 (5H, m), 3.60-3.54 (2H, m), 3.42 (1H,
m), 2.79 (1H, br), 2.51, 2.31 (1H each, m each), 1.67-1.25 (22H,
m), 1.49, 1.34 (3H each, s each), 1.38 (3H, d, J ) 6.7), 0.88
(21) Noda, N.; Miyahara, K.; Kawasaki, T. Chem. Pham. Bull. 1988,
36, 627.

Total Synthesis of Tricolorin A
J . Org. Chem., Vol. 62, No. 24, 1997 8405
3H, t, J ) 6.9); 13C NMR (75.6 MHz, CDCl3) 174.9, 137.2, 129.2,
128.3, 109.9, 102.5, 101.8, 98.9, 83.2, 79.5, 78.4, 75.2, 74.8, 68.9,
66.3, 36.0, 35.7, 34.8, 32.0, 30.6, 29.8, 29.4, 28.5, 28.4, 27.9,
27.0, 26.6, 25.9, 22.7, 16.8, 14.2; ESIMS 713 (M + Na+), 729
system was warmed to rt and stirred for another 0.5 h. To
the resulting mixture was added Et3N (0.1 mL), and the
mixture was diluted with CH2Cl2 (70 mL), washed with 10%
aqueous Na2S2O3 and, ice-water, dried over Na2SO, and
concentrated. Flash chromatography on a silica gel column
(petroleum ether-EtOAc, 20:1) afforded 33 (7 mg, 43%, 48 mg
(M + K+). Anal. Calcd for C38H58O11
: C, 66.07; H, 8.46.
Found: C, 65.88; H, 8.59.
31: [R]19D -38.60 (c 0.27, CHCl3); IR (KBr) 3484, 1751 cm-1
;
2 recovered) as a colorless amorphous solid: [R]19 -11.01 (c
D
1H NMR (300 MHz, CDCl3) 7.50-7.36 (5H, m), 5.55 (1H, s),
5.23 (1H, d, J ) 7.4), 4.91 (1H, t, J ) 8.1), 4.28 (1H, dd, J )
4.8, 10.4), 4.16 (1H, d, J ) 8.3), 4.07 (1H, m), 4.00 (1H, m),
3.92-3.67 (5H, m), 3.50 (2H, m), 3.07 (1H, br), 2.45 (2H, m),
1.53, 1.36 (3H each, s each), 1.75-1.26 (25H, m), 0.88 (3H, t,
J ) 6.2); 13C NMR (75.6 MHz, CDCl3) 173.8, 137.1, 129.2,
128.3, 126.3, 110.0, 101.8, 100.4, 97.3, 80.0, 79.4, 75.2, 75.1,
73.0, 68.8, 68.7, 66.1, 35.1, 33.7, 31.9, 27.9, 26.8, 26.5, 26.33,
26.27, 26.1, 25.2, 23.8, 23.6, 22.6, 16.6; FABMS m/z 690 (M+).
Anal. Calcd for C38H58O11: C, 66.07; H, 8.46. Found: C, 66.22;
H, 8.76.
0.39, CHCl3); IR (KBr) 1743 cm-1; 1H NMR (400 MHz, CDCl3)
7.35-7.26 (20H, m), 5.53 (1H, s), 5.33 (1H, dd, J ) 7.1, 9.3),
5.20 (1H, dd, J ) 6.3), 5.13 (1H, t, J ) 2.2), 5.09 (1H, d, J )
1.6), 5.05 (1H, t, J ) 9.9), 4.98 (1H, d, J ) 1.6), 4.87, 4.59 (1H
each, d, J ) 11.4), 4.73, 4.69 (1H each, d, J ) 11.7), 4.55, 4.51
(1H each, d, J ) 11.7), 4.32-4.26 (2H, m), 4.15-4.09 (3H, m),
4.01 (1H, m), 3.91-3.47 (11H, m), 2.5 (3H, m), 2.2 (1H, m),
1.49, 1.31 (3H each, s each), 1.37 (3H, d, J ) 6.5), 1.26 (6H,
m), 1.15 (3H, m), 1.07 (3H, d, J ) 7.0), 0.89 (6H, m), 0.81 (3H,
m); 13C NMR (75.6 MHz, CDCl3): 175.4, 175.3, 172.3, 139.0,
138.4, 137.1, 129.0, 128.3, 128.2, 128.1, 127.6, 127.4, 127.2,
126.1, 109.7, 101.5, 101.3, 100.5, 98.0, 97.4, 82.1, 80.7, 80.2,
80.0, 79.2, 78.2, 75.7, 75.1, 74.9, 74.7, 73.5, 72.4, 72.2, 72.0,
71.7, 68.8, 68.7, 67.3, 65.2, 41.3, 41.2, 35.3, 34.8, 34.3, 31.9,
30.4, 29.7, 29.2, 27.9, 27.8, 27.7, 26.9, 26.6, 26.5, 26.4, 25.2,
24.0, 22.6, 17.8, 17.4, 16.8, 16.75, 16.7; ESIMS m/z 1445 (M +
Na+), 1468 (M + 2Na+). Anal. Calcd for C81H112O21; C, 68.43;
H, 7.94. Found: C, 68.39; H, 8.14.
Eth yl O-[2,3,4-Tr i-O-ben zyl-1-th io-r-L-r h a m n op yr a n o-
syl]-(1f3)-2,4-d i-O-[2(S)-m eth ylbu tyr yl]-1-th io-r-L-r h a m -
n op yr a n osid e (32). A mixture of 3 (700 mg, 1.47 mmol, 2.5
equiv), 4 (222 mg, 0.59 mmol), and 4 Å MS (1 g) in Et2O-
ClCH2CH2Cl (18 mL, 5:1) was stirred for 15 min under
nitrogen at rt, and then IDCP (1.076 mg, 2.31 mmol) was
added. After being stirred for 0.5 h, the resulting mixture was
filtered through a short column of silica gel and diluted with
Et2O (200 mL). The organic phase was washed with 10%
aqueous Na2S2O3 and ice-water, dried with Na2SO4, and
concentrated. Flash chromatography on a silica gel column
(petroleum ether-EtOAc, 100:3) furnished 32 as a colorless
Tr icolor in A (1). A solution of 33 (127 mg, 0.09 mmol)
and DDQ (94 mg) in CH3CN-H2O (10 mL, 9:1) was refluxed
for 4 h. After being diluted with Et2O (200 mL), the solution
was washed with saturated aqueous NaHCO3 and brine, dried
over Na2SO4, and concentrated. The residue was decolored
by active charcoal and chromatographed to afford a colorless
syrup (92 mg) that was subjected to hydrogenation (H2, 6 MPa)
with catalytic 10% Pd-C in 95% ethanol (5 mL) for 7 h. After
syrup (457 mg, 98%): [R]22 -35.85 (c 1.89, CHCl3); IR (neat)
D
1740 cm-1; 1H NMR (300 MHz, CDCl3) 5.13 (1H, m), 5.12 (1H,
s), 5.02 (1H, t, J ) 9.7), 4.84 (1H, s), 4.79, 4.52 (1H each, d, J
) 11.3), 4.66, 4.56 (1H each, d, J ) 12.2), 4.51, 4.48 (1H each,
d, J ) 11.9), 4.03 (1H, m), 3.95 (1H, dd, J ) 2.4, 9.8), 3.65
(1H, dd, J ) 8.3), 3.63 (1H, s), 3.49 (2H, m), 2.56 (2H, m), 2.38
(1H, m), 2.17 (1H, m), 1.65, 1.57, 1.39, 1.31 (1H each, m each),
1.18 (3H, d, J ) 5.1), 1.09 (3H, d, J ) 5.1), 1.09 (3H, d, J )
6.1), 1.02 (3H, d, J ) 7.1), 0.83 (3H, t, J ) 7.4), 0.76 (3H, t, J
) 7.3); 13C NMR (150 MHz, CDCl3) 14.97, 17.53, 17.84, 25.74,
67.43, 69.01, 72.39, 72.47, 72.91, 73.65, 74.64, 75.46, 75.64,
80.03, 80.17, 82.11, 100.82, 127.26, 127.41, 127.46, 127.50,
128.10, 128.28, 138.38, 138.48, 138.88, 11.66, 11.77, 16.55,
16.65, 26.37, 26.52, 41.09, 41.19, 175.30, 175.89; FABMS m/z
792 (M+). Anal. Calcd for C45H60O10S: C, 68.16; H, 7.63; S,
4.04. Found: C, 68.02; H, 7.74; S, 4.44.
being filtered through
a short column of silica gel and
concentrated, the residue was chromatographed on a silica gel
column (CH2Cl2:CH3OH, 9:1) to give tricolorin A (64 mg, 70%)
as a colorless amorphous solid: [R]20D -27.27 (c 0.89, CH3OH)
(lit.2 [R]D -30.32 (c 1.5, CH3OH); IR (KBr) 3429, 2934, 1739
cm-1; 1H NMR (600 MHz, C5D5N) 5.82-5.76 (3H, m), 5.69 (1H,
t, J ) 9.6), 5.55 (1H, s), 5.50 (1H, br s), 4.77 (1H, m), 4.71 (1H,
m), 4.65 (1H, m), 4.50 (1H, br s), 4.40 (1H, m), 4.34 (1H, m),
4.23 (3H, m), 4.12 (2H, m), 4.01 (1H, br s), 3.89 (1H, m), 3.82
(2H, m), 3.47 (1H, m), 2.98 (1H, m), 2.45(1H, m), 2.31 (1H,
m), 1.70 (3H, d, J ) 5.4), 1.63 (3H, d, J ) 5.4), 1.57 (3H, d, J
) 6.6), 1.16 (3H, d, J ) 7.8), 1.10 (3H, d, J ) 7.2), 0.91 (3H, t,
J ) 6.6), 0.82 (6H, m); 13C NMR (75.6 MHz, C5D5N) 175.6,
175.5, 172.1, 104.5, 102.9, 99.7, 98.2, 80.8, 80.5, 78.8, 76.2, 76.1,
75.8, 74.5, 73.23, 73.18, 73.0, 72.6, 72.4, 72.2, 71.1, 70.4, 69.4,
67.1, 61.1, 41.7, 41.4, 41.3, 35.0, 34.3, 31.9, 31.6, 29.8, 29.4,
27.8, 26.9, 26.7, 26.5, 25.5, 24.6, 23.5, 22.7, 18.4, 18.2, 17.2,
16.83, 16.78, 14.1, 11.7; ESIMS m/z 1046 (M + Na+), 1069 (M
+ 2Na+).
1,3(B)-La ct on e of (S)-1-(H yd r oxyca r b on yl)p en t a d ec-
10-yl O-(2,3,4-Tr i-O-ben zyl-r-L-r h a m n op yr a n osyl)-(1f3)-
2,4-d i-O-(2S-m eth ylbu tyr yl)-r-L-r h a m n op yr a n osyl-(1f2)-
4,6-b e n zylid e n e -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 osid e (33). Meth od A. A mix-
ture of 2 (139 mg, 0.2 mmol), 32 (242 mg, 0.3 mmol), and 4 Å
MS (1 g) in CH2Cl2 (5 mL) was stirred at rt under argon for
15 min. NIS (200 mg, 0.9 mmol) was added followed by a
solution of AgOTf (33 mg) in toluene (0.5 mL) immediately.
After the mixture was stirred for 1 h, Et3N (0.2 mL) was added
to quench the reaction, and the mixture was filtered through
a short column of silica gel and diluted with CH2Cl2 (150 mL).
The solution was washed with 10% aqueous Na2S2O3 and ice-
water, dried over Na2SO4, and concentrated. Flash chroma-
tography on a silica gel column (petroleum ether-EtOAc, 90:
8) afforded 33 (245 mg, 86%) as a colorless amorphous solid.
Meth od B (“On e-P ot” P r oced u r e). A mixture of 3 (11
mg, 0.029 mmol), 4 (16 mg, 0.034 mmol), and 4 Å MS (100
mg) in Et2O-DCE (2 mL, 1/1, v/v) was stirred at rt under
nitrogen for 0.5 h. The mixture was cooled to -15 °C, and
then NIS (9 mg, 0.04 mmol) and a solution of TfOH-DCE (1:
300, ∼20 µL) were added. After stirring for 0.5 h (TLC showed
that 4 was consumed), 4 Å MS (50 mg), 2 (56 mg, 0.04 mmol),
NIS (14 mg, 0.046 mmol), and a catalytic solution of TfOH-
DCE (1:300, ∼20 µL) was added successively. The reaction
Ack n ow led gm en t. We thank the State Science and
Technology Committee of China for financial support.
We are also grateful to Prof. Hou-Ming Wu for 600 MHz
NMR support and to Prof. R. Pereda-Miranda for kindly
affording the authentic sample and 1H and 13C NMR
spectra of tricolorin A.
Su p p or tin g In for m a tion Ava ila ble: Reproductions of 1H
NMR spectra for compounds 1-3, 7, 13, 21, 22, 25, 26, and
29-33, 13C NMR spectra for compounds 1-3, 26, and 30-33,
IR and MS spectra for compounds 1 and 33, and 2D NMR
spectra (ROESY, HMQC, DQCOSY, TOCSY) for 1 (30 pages).
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J O9711450