Ellagitannin chemistry. Evolution of a three-component coupling strategy for the synthesis of the dimeric ellagitannin coriariin A and a dimeric gallotannin analogue

Article abstract of DOI:10.1021/jo0010936

The total synthesis of the dimeric ellagitannin coriariin A is reported. The key reaction to access the dimeric framework was realized early in the synthesis pathway via a bis acylation reaction of a dehydrodigalloyl diacid with 2 equiv of a glucopyranose

Full text of DOI:10.1021/jo0010936

J . Org. Chem. 2000, 65, 8011-8019
8011
Ella gita n n in Ch em istr y. Evolu tion of a Th r ee-Com p on en t
Cou p lin g Str a tegy for th e Syn th esis of th e Dim er ic Ella gita n n in
Cor ia r iin A a n d a Dim er ic Ga llota n n in An a logu e
Ken S. Feldman,* Michael D. Lawlor, and Kiran Sahasrabudhe
Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802
ksf@chem.psu.edu
Received J uly 19, 2000
The total synthesis of the dimeric ellagitannin coriariin A is reported. The key reaction to access
the dimeric framework was realized early in the synthesis pathway via a bis acylation reaction of
a dehydrodigalloyl diacid with 2 equiv of a glucopyranose trichloroacetimidate. The glucose rings
were subsequently functionalized, culminating in a double oxidative cyclization to form stereo-
selectively both (S)-HHDP ester units. This bis acylation strategy was also employed to prepare a
gallotannin analogue of coriariin A whose earlier synthesis by orthoquinone dimerization was
plagued by yield-limiting side reactions.
Dimeric ellagitannins that are C-O linked through the
anomeric galloyl rings constitute a small but biologically
notable subfamily of polyphenolic plant metabolites.1
Screening for antitumor activity among these species
revealed remarkable tumor remissive properties against
mouse xenograft lines for several structurally similar (but
not phylogenetically related) members such as coriariin
A (1) and agrimoniin (2), Figure 1.2 Furthermore, these
data show that the dimeric ellagitannins are much more
effective antitumor agents than their likely monomeric
precursors. Subsequent studies aimed at uncovering the
cellular basis for this activity suggested that coriariin A
and agrimoniin did not directly kill tumor cells, but
rather exerted their effect indirectly through stimulated
production of tumor necrosis factor-R (TNF-R) from
peripheral blood mononuclear cells (PBMCs).2c,d,3 This
cytokine displays tumor-remissive properties, although
systemic toxicity has limited its use in antitumor thera-
pies.4
The broad range of measured antitumor efficacy among
some 45-odd monomeric, dimeric (including 1 and 2), and
trimeric ellagitannins is suggestive of a model for biologi-
cal activity which requires a specific interaction between
(1) (a) Haslam, E. Practical Polyphenolics; Cambridge University
Press: Cambridge, 1998. (b) Feldman, K. S.; Sahasrabudhe, K.;
Quideau, S.; Hunter, K. L.; Lawlor, M. D. In Plant Polyphenols 2:
Chemistry, Biology, Pharmacology, Ecology; Kluwer Academic/Plenum
Publishers: New York, 1999. (c) Okuda, T.; Yoshida, T.; Hatano, T. In
Progress in the Chemistry of Organic Natural Products; Herz, W.,
Kirby, G. W., Moore, R. E., Steglich, W., Tamm, Ch., Eds.; Springer-
Verlag: New York, 1995; Vol. 66, p 1-117, and references therein. (d)
Hatano, T.; Hattori, S.; Okuda, T. Chem. Pharm. Bull. 1986, 34, 4092.
(e) Okuda, T.; Yoshida, T.; Kuwahara, M.; Memon, M. U.; Shingu, T.
Chem. Pharm. Bull. 1984, 32, 2165.
F igu r e 1. Representative O(1)-O(1′) linked dimeric ellagi-
tannins.
the tannin and an endogenous receptor(s), plausibly
associated with the PBMCs, to initiate TNF-R release.
Identifying the putative PBMC-based receptor(s) for the
active ellagitannins may provide the impetus for further
developing ellagitannins, or ellagitannin-inspired ana-
logues, as biological response modifiers within the context
of antitumor chemotherapies. In this vein, synthesis of
the naturally occurring species, as well as rationally
designed analogues, may provide appropriate probe
molecules to aid in this task.
(2) (a) Miyamoto, K.; Kishi, N.; Koshiura, R. J apan J . Pharmacol.
1987, 43, 187. (b) Miyamoto, K.; Kishi, N.; Koshiura, R.; Yoshida, T.;
Hatano, T.; Okuda, T. Chem. Pharm. Bull. 1987, 35, 814. (c) Miyamoto,
K.; Murayama, T.; Nomura, M.; Hatano, T.; Yoshida, T.; Furukawa,
T.; Koshiura, R.; Okuda, T. Anticancer Res. 1993, 13, 37. (d) Murayama,
T.; Kishi, N.; Koshiura, R.; Takagi, K.; Furukawa, T.; Miyamoto, K.
Anticancer Res. 1992, 12, 1471. (e) Miyamoto, K.; Nomura, M.;
Murayama, T.; Furukawa, T.; Hatano, T.; Yoshida, T.; Koshiura, R.;
Okuda, T. Biol. Pharm. Bull. 1993, 16, 379.
(3) Feldman, K. S.; Sahasrabudhe, K.; Smith, R. S.; Scheuchenzuber,
W. J . Biorg. Med. Chem. Lett. 1999, 9, 985.
(4) Barbara, J . A. J .; Ostade, X. v.; Lopez, A. F. Immunol. Cell Biol.
1996, 74, 434.
10.1021/jo0010936 CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/21/2000

8012 J . Org. Chem., Vol. 65, No. 23, 2000
Feldman et al.
Sch em e 1
Sch em e 2
Synthesis strategies in the ellagitannin area have
largely fallen into two camps, depending upon whether
the bis galloyl-to-HHDP (hexahydroxydiphenoyl) trans-
formation occurs before5a-d or after5e-m attachment of the
galloyl ester moieties to the glucopyranose core. In
addition, the methodology for forming the key biaryl C-C
bond upon HHDP synthesis has utilized both reductive
(e.g., Ullmann-type)5e,f,m and oxidative (e.g., Wessely
type)5a-d couplings. Several syntheses of permethyl ella-
gitannins have been recorded, in particular using reduc-
tive coupling methodologies, but as yet exhaustive de-
methylation to unveil the product polyphenol remains
problematic.5e,f,l In contrast, HHDP synthesis by oxidative
phenolic coupling has proven to be tolerant of phenolic
protecting groups that are much more easily removed,
and this strategy has led to the preparation of several
monomeric HHDP-containing ellagitannins.5a-d
Application of this oxidative coupling strategy, which
was patterned after much earlier biosynthesis specula-
tion,6 to the more complex dimeric ellagitannin target
coriariin A (1) requires additional attention directed
toward the dehydrodigalloyl ether linking unit (cf. 1).
Continuing with the biosynthesis speculation which
undergirds the C-C galloyl couplings, a plausible in vivo
construction of coriariin A might pass through the
monomeric ellagitannin tellimagrandin II (4), Scheme 1.
Oxidation of the anomeric galloyl unit of 4 (to 4a ) might
then provide an electrophilic partner for coupling with
the nucleophilic phenol at the meta position of the
anomeric galloyl ester on a second molecule of tellima-
grandin II. This tellimagrandin II oxidative dimerization
biosynthesis speculation then can be used to formulate
a synthesis plan for coriariin A which centers on an
oxidative union between two appropriately functionalized
derivatives of 4.
Even within the context of this biosynthesis hypothesis,
the precise nature of the oxidized form of the O(1) galloyl
unit of tellimagrandin II remains a matter of conjecture.
Speculation can run the gamut from single-electron
oxidized species (e.g., radical cation, phenoxy radical) to
two-electron deficient derivatives (e.g., cyclohexadienonyl
cation, orthoquinone). While each of these species could,
in principle, join with the appropriate nucleophilic phenol
to fashion the diaryl ether bond, some circumstantial
evidence implicates the orthoquinone species 5a as a
plausible reactive intermediate, Scheme 2. Thus, the
benzodioxene portion of the naturally occurring ellagi-
tannin syzyginin B (9)7 may, in fact, be biosynthesized
via hetero Diels-Alder-type cycloaddition of the ortho-
quinones 6 and 7. Taking a cue from this biosynthesis
speculation, a Diels-Alder dimerization/reductive rear-
rangement sequence with the monomeric pentagalloyl-
(5) (a) Feldman, K. S.; Ensel, S. M. J . Am. Chem. Soc. 1994, 116,
3357. (b) Feldman, K. S.; Ensel, S. M.; Minard, R. D. J . Am. Chem.
Soc. 1994, 116, 1742. (c) Feldman, K. S.; Sambandam, A. J . Org. Chem.
1995, 60, 8171. (d) Feldman, K. S.; Smith, R. S. J . Org. Chem. 1996,
61, 2606. (e) Nelson, T. D.; Meyers, A. I. J . Org. Chem. 1994, 59, 2577.
(f) Lipshutz, B. H.; Liu, Z.-P.; Kayser, F. Tetrahedron Lett. 1994, 35,
5567. (g) Khanbabaee, K.; Lo¨tzerich, K. Liebigs Ann. 1997, 1571. (h)
Khanbabaee, K.; Lo¨tzerich, K. J . Org. Chem. 1998, 63, 8723. (i)
Khanbabaee, K.; Schulz, C.; Lo¨tzerich, K. Tetrahedron Lett. 1997, 38,
1367. (j) Khanbabaee, K.; Lo¨tzerich, K.; Borges, M.; Groâer, M. J . Prakt.
Chem. 1999, 341. (k) Itoh, T.; Chika, J .-i. J . Org. Chem. 1995, 60, 4968.
(l) Itoh, T.; Chika, J .-i.; Shirakami, S.; Ito, H.; Yoshida, T.; Kubo, Y.;
Uenishi, J .-i. J . Org. Chem. 1996, 61, 3700. (m) Dai, D.; Martin, O. R.
J . Org. Chem. 1998, 63, 7628.
(6) (a) Schmidt, O. T. Fortschr. Chem. Org. Naturstoffe 1956, 13,
70. (b) Schmidt, O. T.; Mayer, W. Angew. Chem. 1956, 68, 103. (c)
Gupta, R. K.; Al-Shafi, S. M. K.; Layden, K.; Haslam, E. J . Chem. Soc.,
Perkin Trans. 1 1982, 2525. (d) Haddock, E. A.; Gupta, R. K.; Haslam,
E. J . Chem. Soc., Perkin Trans. 1 1982, 2535.
(7) Tanaka, T.; Orii, Y.; Nonaka, G.-i.; Nishioka, I.; Kouno, I.
Phytochemistry 1996, 43, 1345.

Ellagitannin Chemistry
Sch em e 3
J . Org. Chem., Vol. 65, No. 23, 2000 8013
Sch em e 4
based orthoquinone 10 was explored for the synthesis of
the dehydrodigalloyl ether unit in the model system 11.8
A convergent, two-component synthesis strategy for
coriariin A was designed with these precedents in hand,
Scheme 3. Accordingly, acquisition of tellimagrandin II-
derived orthoquinone 5b became the focal point of this
first-generation synthesis. As events transpired, alterna-
tive strategies had to be developed which utilized a three-
component coupling between diacyl derivatives 16 and
two glucopyranose cores (e.g., 12-15). Electronic tuning
of the glucopyranose donors was instrumental in the
successful execution of this strategy, and ultimately the
target molecule was synthesized in good overall yield and
with complete control of all of the stereochemical ele-
ments from 15 and 16a .8
conditions resulted in degradation of the orthoquinone.
Exploratory Diels-Alder dimerization chemistry with
impure 5b did not afford any detectable coriariin A-like
dimeric products. Examination of alternative oxidants
(CAN, Ag2O, hypervalent iodine reagents) led to the
10
identification of PhI(OTFA)2 (PIFA) as the most prom-
ising candidate for the oxidation of catechol 19. Treat-
ment of 19 with PIFA at -40 °C followed by warming to
0 °C effected complete conversion to the orthoquinone 5b,
as determined by 1H NMR spectroscopy of the crude
reaction mixture. One of the byproducts of this reaction,
trifluoroacetic acid, was easily removed by concentration
of the reaction solution. Attempts to completely separate
the other byproduct, iodobenzene, by trituration with
hexane were unsuccessful.
Resu lts a n d Discu ssion
Cor ia r iin A. Stereoselective installation of the dehy-
drodigalloyl ether unit linking the two glucose cores
represents the primary challenge for synthesis presented
by coriariin A. The initial synthesis strategy was pat-
terned after the presumed tellimagrandin II dimerization
shown in Scheme 1. Extension of the model transforma-
tion 10 f 11 to the synthesis of coriariin A required
execution of the same reaction sequence on a sugar
derivative containing an intact perbenzylated O(4)-O(6)
HHDP unit (5b, Scheme 2). Toward this end, the known
perbenzyl protected HHDP-containing glucopyranose
derivative 139a was treated with galloyl chloride 17 in
the presence of triethylamine to provide exclusively the
â-esterified product 18 (Scheme 4). Subsequent desily-
lation of 18 gave the catechol 19, the critical intermediate
in the proposed tellimagrandin II dimerization strategy.
Oxidation of 19 to the orthoquinone Diels-Alder
substrate 5b proceeded smoothly with orthochloranil, but
isolation of the product was much more difficult than in
the case of the model orthoquinone 10. Identical reaction
conditions that led to precipitation of pure 10 failed to
deposit 5b. The use of lower reaction temperatures (-78
to -40 °C) and several different solvents or solvent
combinations did not lead to separation of 5b from the
oxidation byproduct tetrachlorocatechol. Attempted pu-
rification by SiO2 chromatography under a variety of
Repeated efforts to effect B(OAc)3-mediated Diels-
Alder dimerization of 5b contaminated with PhI failed
to furnish any detectable quantities of benzodioxene-
1
derived products, as judged by analysis of the H NMR
and FABMS spectra of the reaction mixture. The signals
corresponding to orthoquinone 5b had disappeared, but
eventual completion of the dehydrodigalloyl ether form-
ing sequence led only to monomeric products (e.g.,
perbenzylated tellimagrandin II). Efforts to identify a
more suitable Lewis acid catalyst thus far have been
unsuccessful, as have purely thermal Diels Alder cy-
cloaddition attempts. These puzzling results, in light of
the presumably secure chemistry of the similar substrate
10, prompted a reanalysis of the model system dimer-
ization. Careful examination of several different batches
of debenzylated final product “11” revealed that variable
ratios of three difficultly separable components, in fact,
were present: the expected dimer 11, â-pentagalloylglu-
cose (3), and 1-O-acetoxytetragalloylglucose, a species
plausibly arising from interaction of B(OAc)3 with an
O(1)-galloylated glucopyranose derivative. Thus, in ac-
tuality the dimerization of 10 appears to provide only
small and variable quantities of the dehydrodigalloyl
ether-containing product 11 (best case e 10% from 10).
While the dimerization results with 5b were disappoint-
(8) Feldman, K. S.; Lawlor, M. D. J . Am. Chem. Soc. 2000, 122, 7396.
(9) (a) Feldman, K. S.; Sahasrabudhe, K. J . Org. Chem. 1999, 64,
209. (b) Sahasrabudhe, K. Ph.D. Thesis, The Pennsylvania State
University, 1998.
(10) Varvoglis, A. The Organic Chemistry of Polycoordinated Iodine;
VCH: New York, 1992.

8014 J . Org. Chem., Vol. 65, No. 23, 2000
Feldman et al.
ing, at least now they are more in line with the revised
picture of the model system dimerization.
Recourse was made to an alternative three-component
coupling approach for coriariin A synthesis, as the failure
of the direct Diels-Alder-based tellimagrandin II dimer-
ization strategy became apparent. While lacking a com-
pelling biosynthetic rationale, this second-generation
acylation-based assembly sequence (Scheme 3, path b,
13 + 16b) seemed more solidly grounded on reliable
precedent (i.e., 13 + tribenzylgalloyl chloride provided
the anomeric acylation product in 41% yield).9a Toward
this end, the dehydrodigalloyl chloride 16b9a or fluoride
16c,9b readily available from the diacid 16a ,9a was mixed
in the presence of base with 2 equiv of either the model
alcohol 129a or, independently, the HHDP-containing
coriariin A precursor 13, but no dimeric tannin species
could be identified in either case. Interestingly, even
monoacylated products, as might have been derived from
alcohol addition to the more exposed acyl halide (* in 16b)
could not be detected. Thus, an inexplicable divergence
of reaction pathways between the seemingly secure model
system (Scheme 4, 13 + 17) and the “real” system, 13 +
16b, served to underscore marked reactivity differences
between the monomeric galloyl chlorides and the bis acid
chloride 16b (or fluoride 16c).
The lack of correspondence between the successful
model acylations and the more complex systems required
for coriariin A suggested that some fresh insights might
be welcome. The arming/disarming strategies for ano-
meric etherification popularized by Fraser-Reid provided
some guidance in this regard.12 The Fraser-Reid work
demonstrated that the electron demand at O(2) of the
glucopyranose core significantly influenced the rate of
substitution when reactive anomeric leaving groups (e.g.,
oxonium ions) were displaced by hydroxyl nucleophiles.
The extrapolation of this methodology to anomeric es-
terification utilizing the arguably less potent leaving
group trichloroacetimidate and carboxylate nucleophiles,
as is required for coriariin A synthesis, did not seem
unconscionable at this stage of the project. Thus, ano-
meric trichloroacetimidate displacement by the evidently
more weakly nucleophilic diacid 16a might benefit from
incorporation of a more electron-releasing substituent at
O(2) than the galloyl group of 22. Driven by this premise,
a third-generation synthesis plan for coriariin A was
devised, Scheme 5. This route relied on early installation
of the diaryl ether unit and later elaboration of the HHDP
moieties on both glucopyranose cores. In this approach,
the more electron releasing O(2) and O(3) TBDMS ethers
of 15 are anticipated to enhance the prospects for
3-component coupling via double displacement of the
trichloroacetimidate groups with diacid 16a . Conversion
of all of the glucose protecting groups in 26a into the
appropriately functionalized galloyl ester-bearing species
28b then sets the stage for the second key transformation
of the synthesis, the double oxidative cyclization of this
octagalloylated coriariin A precursor to form the requisite
HHDP units.
Strategically related companion studies that featured
displacement of an anomeric leaving group within a
glucopyranose core by a nucleophilic gallic acid derivative
showed more promise. For example, the combination of
the cesium salt of diacid 16a with the electrophilic
partner tetraacetoxybromoglucopyranose (20) provided
dimer 21 in moderate yield (eq 1). However, application
The synthesis of trichloroacetimidate 15 began with
the known acetal 2513 (Scheme 5). Protection of the O(2)
and O(3) hydroxyl groups of 25 as TBDMS ethers was
followed by selective photochemical removal of the O(1)-
o-nitrobenzyl ether. The resulting anomeric alcohol was
activated for coupling by conversion to the trichloroace-
timidate 15 in excellent yield, as per the earlier prepara-
tion of the galloylated glucopyranosyl trichloroacetimi-
date 22. Clean three-component coupling was effected by
treatment of 15 (2 equiv) with diacid 16a in refluxing
benzene to furnish the diglucopyranosyl dehydrodigalloyl
diester 26a as a single stereoisomer in reproducibly good
yield. The facility of this acylation with the O(2), O(3)-
of this transformation to the coriariin A effort was
thwarted by an inability to access the requisite anomeric
halides 14 from alcohol 13. Alternatively, the trichloro-
acetimidate 22 was prepared in good yield from alcohol
12, and this version of an activated glucopyranosyl donor
combined smoothly with the monomeric gallic acid de-
rivative 23 in refluxing toluene to afford the â-O(1)-
acylated product 24 in acceptable yield (eq 2).11 Dis-
appointingly, but perhaps not surprisingly at this point,
modification of this procedure to accomplish a double
acylation with diacid 16a and 2 equiv of 22 returned only
unreacted starting materials. Once again, the muted
reactivity of the diaryl ether diacid 16a was not ad-
equately anticipated by a monomeric analogue, the
seemingly quite similar species 23.
(12) Fraser-Reid, B.; Madsen, R. I. In Preparative Carbohydrate
Chemistry; Hanessian, S., Ed.; Marcel Dekker: New York, 1997.
Earlier work that describes the electronic influence of glucopyranose
substituents on chemistry at the anomeric position can be found in:
(b) Paulsen, H. Angew. Chem., Int. Ed. Engl. 1982, 21, 155. (c) Capon,
B. Chem. Rev. 1969, 69, 407. (d) Feather, M. S.; Harris, J . F. J . Org.
Chem. 1965, 30, 153.
(11) (a) Schmidt, R. R.; J ung, K.-H. In Preparative Carbohydrate
Chemistry; Hanessian, S., Ed. Marcel Dekker: New York, 1997. (b)
Schmidt, R. R.; Michel, J . J . Carbohydr. Chem. 1985, 4, 141. (c)
Schmidt, R. R.; Michel, J . Angew. Chem., Int. Ed. Engl. 1980, 19, 731.
(13) Prepared in three steps by a modification of the previously
published procedure, see: (a) Feldman, K. S.; Sambandam, A. J . Org.
Chem. 1995, 60, 8171. (b) Nicolaou, K. C.; Schreiner, E. P.; Stahl, W.
Angew. Chem., Int. Ed. Engl. 1991, 30, 585.

Ellagitannin Chemistry
Sch em e 5
J . Org. Chem., Vol. 65, No. 23, 2000 8015
Sch em e 6
Construction of the requisite HHDP units commenced
with deprotection of the acetal moieties in 26c by
treatment with iodine16 to provide the corresponding
tetraol which was esterified immediately with gallic acid
derivative 27 (4 equiv) to afford the fully galloylated
dimer 28a in good yield. The key bis oxidative cyclization
substrate 28b was prepared by desilylation of tetrakis-
(TBDMS) ether 28a with acetic acid-buffered n-Bu4NF.
As with the simpler substrate 26a , the acute sensitivity
of the dehydrodigalloyl ester linkages to nucleophilic
attack necessitated use of the acetic acid additive. In-
tramolecular Pb(OAc)4-mediated oxidative coupling of
tetragalloylphenol 28b under Wessely17 oxidation condi-
tions afforded a complex mixture of (inconsequential)
regioisomeric protected bis (S)-HHDP containing prod-
ucts. This result is in accord with earlier glucopyranosyl-
based digalloyl f HHDP transformations.5a-d Hydro-
genolysis of the entire complement of protecting groups
within the purified but still regioisomerically complex
cyclization product mixture furnished a single product,
coriariin A (1), in excellent yield as a light gray solid
following trituration with ether and hexane. A compari-
1
son of the H NMR, 13C NMR, mass spectrum, and CD
spectrum of the synthesized material with those reported
1
for coriariin A,1d as well as a direct comparison of the H
NMR spectra of the synthetic and the plant-derived
material (kindly provided by Professor T. Yoshida, Okaya-
ma University), verified that natural coriariin A had been
synthesized.
disilylated glucopyranose derivative 15, in contrast to the
failures with the analogous galloylated substrates (e.g.,
22) is consistent with the O(2) electron-demand hypoth-
esis discussed above. Thus, there may indeed be predict-
able O(2)-localized electronic influences for anomeric
trichloroacetimidate acylation chemistry much as there
are in the more familiar anomeric etherifications.
Three distinct sets of hydroxyls must be selectively and
sequentially deprotected en route to the penultimate
coriariin A intermediate 28b. Deprotection of the TBDMS
ethers of 26a with acetic acid-buffered n-Bu4NF fur-
nished the tetraol 26b in good yield.14 The use of this
reagent combination was crucial for preserving the
sensitive dehydrodigalloyl ester bonds, as other common
desilylation protocols (unbuffered n-Bu4NF, TAS-F, HF,
HF‚pyridine) led to partial or complete anomeric ester
hydrolysis. Galloylation at the O(2) and O(3) positions
of both glucopyranose rings in 26b with tribenzylgallic
acid (23) (4 equiv) was accomplished using modified
Steglich esterification conditions to afford the tetragal-
loylated substrate 26c.15
Mod el Dim er 11. The newly recognized difficulties
endemic in the Diels-Alder dimerization of model system
10 argued for the exploration of the alternative three-
component Schmidt trichloroacetimidate acylation chem-
istry for the preparation of a pure sample of dimer 11.
The initial synthesis plan was designed to consolidate
protecting groups since this less complex system lacked
the HHDP unit of coriariin A, Scheme 6. Thus, the
tetrasilylated trichloroacetimidate 31 was anticipated to
serve as the glucopyranose donor in a coupling reaction
with diacid 16a . The preparation of this carbohydrate
component began with the known tetraol 29.13 Protection
of the hydroxyl groups as TBDMS ethers was followed
by selective photochemical removal of the O(1)-o-ni-
trobenzyl ether. Surprisingly, the resulting alcohol 30
1
was found to exist in the C4 conformation as evidenced
by the small ring proton coupling constants (J 1,2 ) 4.4,
3.5 Hz). This observation is precedented in pyranose
systems bearing bulky O(3) and O(4) substituents in a
(14) (a) Liu, P.; Panek, J . S. J . Am. Chem. Soc. 2000, 122, 1235. (b)
Smith, A. B., III; Ott, G. R. J . Am. Chem. Soc. 1998, 120, 3935. (c)
Otera, J .; Niibo, Y.; Nozaki, H. Tetrahedron Lett. 1992, 33, 3655.
(15) (a) Neises, B.; Steglich, W. Angew. Chem., Int. Ed. Engl. 1978,
17, 522. (b) Keck, G. E.; Boden, E. P. J . Org. Chem. 1985, 50, 2394.
(16) Szarek, W. A.; Zamojski, A.; Tiwari, K. N.; Ison, E. R. Tetra-
hedron Lett. 1986, 27, 3827.
(17) Bubb, W. A.; Sternhell, S. Tetrahedron Lett. 1970, 4499.

8016 J . Org. Chem., Vol. 65, No. 23, 2000
Feldman et al.
trans disposition.18 The effect of this unanticipated
development on the synthesis route was readily apparent
as treatment of the alcohol 30 with sodium hydride and
trichloroacetonitrile in benzene gave a complex mixture
of products containing two anomeric trichloroacetimi-
dates. Similar results were obtained with DBU as base
in CH2Cl2. Attempted purification of the crude reaction
mixture by silica gel chromatography resulted in decom-
position of the trichloroacetimidates and recovery of
alcohol 30. Without a secure route to the desired trichlo-
roacetimidate 31, this route was abandoned.
The model dimer 11 was finally prepared from an
advanced intermediate in the coriariin A synthesis,
tetraol 32, eq 3. Acylation of 32 with gallic acid derivative
23 furnished the fully galloylated dimer in excellent yield.
Hydrogenolysis of all 29 benzyl ether protective groups
within this species provided the gallotannin model dimer
11 in good yield as a light gray solid following trituration
with dichloromethane and hexane. This species was
formed free of monomeric contaminants, and it exhibited
spectral data completely consistent with the assigned
structure.
tially over three batches of 3 Å molecular sieves. Lead
tetraacetate was recrystallized from acetic acid and stored in
an inert atmosphere glovebox. Reaction product solutions and
chromatography fractions were concentrated using a rotary
evaporator at approximately 20 mmHg and then at ca. 0.1
mmHg (vacuum pump). Column chromatography was per-
formed using 32-63 µm silica gel and the indicated solvent.
Chemical shifts are reported in δ units using tetramethylsilane
(TMS) or acetone as an internal standard for 1H NMR and
chloroform as the internal standard for 13C NMR. Low- and
high-resolution fast atom bombardment (FAB) mass spectra
were run at the University of Texas at Austin. Circular
dichroism (CD) measurements used the wavelength range
200-300 nm, scanning at 1.0 nm intervals with an averaging
time of 8.0 s at 25 °C.
1-O-(3,4-ter t-Bu t yld im et h ylsilyloxy-5-b en zyloxyb en -
zoyl)-2,3-bis(3,4,5-tr iben zyloxyben zoyl)-4,6-(3,4,5,3′,4′,5′-
h exa ben xyloxyd ip h en oyl)-â-D-glu cop yr a n osid e (18). To
a solution of 4,6-(3,4,5,3′,4′,5′-hexabenzyloxy)diphenoyl-2,3-bis-
(3,4,5-tribenzyloxybenzoyl)-â-D-glucopyranose (13) (100 mg,
0.05 mmol) and 3,4-di-tert-butyldimethylsilyloxy-5-benzyloxy-
benzoyl chloride (17) in 2 mL of dry CH2Cl2 was added
triethylamine (22 µL, 0.15 mmol). The reaction mixture was
stirred at room temperature for 18 h and then treated with 5
mL of 1 M HCl. After extraction with 10 mL of EtOAc, the
organic layer was separated and washed with water and brine,
dried over Na2SO4, filtered, and concentrated. Purification of
the residue by flash column chromatography, eluting with
10%-25% EtOAc in hexanes, furnished 90 mg (72%) of
anomeric ester 18 as a white solid froth: IR (CDCl3) 1732 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 7.54-6.77 (m, 73 H), 6.09 (d, J
) 7.9 Hz, 1 H), 5.85-5.77 (m, 2 H), 5.52-5.26 (m, 2 H), 5.24-
4.74 (m, 26 H), 4.36 (dd, J ) 9.6, 5.7 Hz, 1 H), 4.12 (d, J )
13.2 Hz, 1 H), 0.98 (s, 9 H), 0.87 (s, 9 H), 0.33 (s, 6 H), 0.25 (s,
6 H); 13C NMR (CDCl3, 90 MHz) δ 167.4, 166.8, 165.8, 164.6,
164.5, 152.58, 152.5, 152.3, 151.3, 147.9, 144.5, 143.2, 143.1,
142.4, 137.7, 137.6, 137.5, 137.41, 137.4, 136.4, 136.1, 128.6,
128.5, 128.4, 128.3, 128.23, 128.2, 128.04, 128.0, 127.92,
127.90, 127.7, 127.6, 127.5, 127.3, 127.1, 126.8, 123.8, 123.7,
123.5, 119.9, 116.1, 109.5, 109.4, 107.9, 92.9, 77.3, 77.2, 77.0,
76.6, 75.4, 75.1, 74.9, 73.4, 72.7, 71.4, 71.3, 71.2, 71.1, 70.2,
63.0, 26.1, 25.8, 18.6, 18.5. Anal. Calcd for C144H136O26Si2: C,
73.97; H, 5.82. Found: C, 74.08; H, 5.86.
1-O-(2-Ben zyloxy-4,5-d ih yd r oxyben zoyl)-2,3-bis(3,4,5-
t r ib en zyloxyb en zoyl)-4,6-(3,4,5,3′,4′,5′-h exa b en zyloxy-
d ip h en oyl)-â-D-glu cop yr a n osid e (19). A solution of silyl
ether 18 (200 mg, 0.09 mmol) in 2 mL of THF was treated
with n-Bu4NF (1 M in THF, 0.135 mL, 0.135 mmol) and stirred
at room temperature for 45 min. The reaction mixture was
diluted with Et2O and poured over ice-cold 1 M H3PO4. The
organic phase was separated and washed with water and
brine, dried over Na2SO4, filtered, and concentrated. The
residue was purified by flash column chromatography, eluting
with 10-50% EtOAc in hexanes, to afford 120 mg (67%) of
phenol 19: IR (CH2Cl2) 3538, 1734 cm-1; 1H NMR (CDCl3, 300
MHz) δ 7.49-6.82 (m, 73 H), 6.15 (d, J ) 8.4 Hz, 1 H), 5.96
(bs, 1 H), 5.86-5.74 (m, 2 H), 5.55 (bs, 1 H), 5.52-5.41 (m, 2
H), 5.38-4.74 (m, 26 H), 4.37 (dd, J ) 6.1, 9.9 Hz, 1 H), 4.10
(d, J ) 13.1 Hz, 1 H); 13C NMR (CDCl3, 90 MHz) δ 167.4, 166.8,
165.7, 164.8, 164.3, 152.64, 152.62, 152.60, 152.5, 152.3, 152.2,
145.7, 144.8, 144.4, 143.8, 143.1, 143.0, 138.1, 137.7, 137.6,
137.5, 137.4, 137.3, 136.4, 136.3, 135.6, 128.8, 128.7, 128.6,
128.54, 128.5, 128.45, 128.43, 128.4, 128.3, 128.23, 128.2,
128.1, 128.03, 128.0, 127.96, 127.91, 127.86, 127.84, 127.74,
127.7, 127.6, 127.54, 127.5, 127.3, 123.8, 123.7, 123.6, 123.4,
119.9, 111.9, 109.4, 109.3, 107.9, 107.8, 106.7, 92.9, 77.4, 77.2,
77.0, 76.6, 75.5, 75.4, 75.1, 75.0, 74.8, 73.3, 72.6, 71.6, 71.5,
71.2, 71.1, 70.2, 63.0. Anal. Calcd for C132H108O26: C, 75.14;
H, 5.12. Found: C, 74.84; H, 5.25.
A stereoselective synthesis of the naturally occurring
dimeric ellagitannin coriariin A (1) was accomplished in
11 steps from known diol 25. The route features the first
example of a double Schmidt-type acylation between a
dehydrodigalloyl diacid and 2 equiv of a glucopyranosyl
trichloroacetimidate to assemble a dimeric ellagitannin
framework, a transformation made successful only after
finely tuning the electronic characteristics of the glu-
copyranosyl donor. In addition, the double oxidative
cyclization of an octagalloyl substrate establishes the
utility of this Wessely oxidation-based methodology in the
synthesis of dimeric ellagitannins bearing a hydrolyti-
cally sensitive dehydrodigalloyl diester linking unit.
Finally, extension of this bis acylation methodology to a
simple tetragalloylglucopyranose derivative afforded a
coriariin A analogue featuring uncoupled O(4)/O(6) gal-
loyl units, a compound not easily prepared in pure form
through orthoquinone dimerization-based methodology.
Exp er im en ta l Section
Gen er a l Meth od s. All reactions were performed in flame-
dried glassware under a positive pressure of argon with
magnetic stirring. Commercial-grade reagents and solvents
were used without further purification except as indicated
below. Dichloromethane, 2,6-lutidine, pyridine, and benzene
were distilled from calcium hydride. THF was distilled from
sodium benzophenone ketyl or dianion. Methanol was distilled
from magnesium. N,N-Dimethylformamide was dried sequen-
Dim er 21. A solution of 3,4,5,3′,4′-pentabenzyloxydehy-
drodigallic acid (16a ) (25 mg, 0.032 mmol) and Cs2CO3 (10 mg,
0.031 mmol) in 2 mL of MeOH was stirred for 2 h at room
temperature. The solvent was removed to furnish the cesium
salt as a white solid residue. A solution of tetracetoxybromo-
R-D-glucose (20) (26 mg, 0.063 mmol) in 2 mL of DMF was
(18) (a) Shuto, S.; Terauchi, M.; Yahiro, Y.; Abe, H.; Ichikawa, S.;
Matsuda, A. Tetrahedron Lett. 2000, 41, 4151. (b) Yahiro, Y.; Ichikawa,
S.; Shuto, S.; Matsuda, A. Tetrahedron Lett. 1999, 40, 5527. (c) Walford,
C.; J ackson, R. F. W.; Rees, N. H.; Clegg, W.; Heath, S. L. J . Chem.
Soc., Chem. Commun. 1997, 1855. (d) Hosoya, T.; Ohashi, Y.; Matsu-
moto, T.; Suzuki, K. Tetrahedron Lett. 1996, 37, 663.

Ellagitannin Chemistry
J . Org. Chem., Vol. 65, No. 23, 2000 8017
added to the cesium salt and the resulting mixture was stirred
at room temperature for 20 h. The reaction mixture was
partitioned between 4 mL of Et2O and 4 mL of water. The
layers were separated and the organic layer was washed
several times with water to remove the DMF, then washed
with brine, dried over Na2SO4, filtered and concentrated.
Purification of the oily residue by flash column chromatogra-
phy furnished 32 mg (41%) of the dimeric product 21 as a white
3.80-3.74 (m, 1 H, â), 3.70-3.64 (m, 3 H, R,â), 3.54-3.45 (m,
3 H, â), 3.39 (t, J ) 9.3 Hz, 1 H, R), 3.17 (s, 1 H, â), 3.16 (d, J
) 1.6 Hz, R), 0.94 (s, 9 H, R), 0.92 (s, 9 H, â), 0.80 (s, 18 H,
R,â), 0.15 (s, 6 H, R,â), 0.13 (s, 3 H, R), 0.12 (s, 3 H, â), 0.03 (s,
6 H, R,â), -0.03 (s, 6 H, R,â); 13C NMR (90 MHz, CDCl3) R
anomer δ 137.2, 129.0, 128.1, 126.5, 102.4, 81.9, 74.9, 72.0,
69.1, 62.7, 26.0, 26.0, 18.2, 18.1, -3.41, -3.98, -4.17, -4.54.
MS (+ESI) 497 (MH+, 15). Anal. Calcd for C25H44O6Si2: C,
60.44; H, 8.93. Found: C, 60.68; H, 9.14.
1
solid: IR (CH2Cl2) 1757 cm-1; H NMR (CDCl3, 300 MHz) δ
7.53-7.07 (m, 27 H), 6.85 (d, J ) 1.9 Hz, 1 H), 5.86 (d, J ) 7.5
Hz, 1 H), 5.73 (d, J ) 7.9 Hz, 1 H), 5.36-5.10 (m, 14 H), 4.98-
4.73 (m, 2 H), 4.31-4.24 (m, 2 H), 4.11-3.91 (m, 2 H), 3.89-
3.80 (m, 2 H), 2.10-1.59 (m, 24 H); 13C NMR (CDCl3, 50 MHz)
δ 170.6, 170.1, 169.4, 163.9, 161.1, 152.8, 152.6, 150.0, 148.0,
146.4, 143.7, 143.6, 142.6, 136.5, 129.4, 129.2, 129.1, 129.0,
127.7, 127.3, 127.1, 123.0, 117.3, 77.4, 77.0, 76.6, 75.6, 73.5,
71.9, 71.0, 67.1, 61.4, 22.7, 21.4, 21.3, 21.2, 19.9, 19.8, 19.7,
4,6-O-Ben zylid en e-2,3-bis(ter t-bu tyld im eth ylsilyl)-r-D-
glu cop yr a n osyl tr ich lor oa cetim id a te (15). Sodium hydride
(13 mg, 0.33 mmol) was degreased by washing with hexanes,
dried in vacuo, and suspended in 1 mL of benzene. A solution
of 4,6-O-benzylidene-2,3-bis(tert-butyldimethylsilyl)-D-gluco-
pyranose (132 mg, 0.266 mmol) in 4 mL of benzene was added
via cannula. The reaction mixture was stirred at room tem-
perature for 10 min, and trichloroacetonitrile (0.280 mL, 2.79
mmol) was added slowly dropwise to control vigorous bubbling.
The resulting light orange reaction mixture was stirred for 4
h, diluted with 8 mL of water, and extracted with 50 mL of
Et2O. The organic phase was washed with 20 mL of brine,
dried over Na2SO4, filtered and concentrated. The orange
residue was purified by flash column chromatography, eluting
with 5-20% EtOAc in hexanes, to afford 153 mg (90%) of 15
as a colorless oil: IR (CDCl3) 3346, 1672 cm-1; 1H NMR (CDCl3,
300 MHz) δ 8.60 (s, 1 H), 7.50-7.45 (m, 2 H), 7.36-7.33 (m, 3
H), 6.29 (d, J ) 3.4 Hz, 1 H), 5.47 (s, 1 H), 4.29 (dd, J ) 10.2,
4.9 Hz, 1 H), 4.14 (t, J ) 8.9 Hz, 1 H), 4.00 (td, J ) 9.8, 4.9
Hz, 1 H), 3.82 (dd, J ) 8.7, 3.4 Hz, 1 H), 3.70 (t, J ) 10.2 Hz,
1 H), 3.50 (t, J ) 9.4 Hz, 1 H), 0.88 (s, 9 H), 0.83 (s, 9 H), 0.14
(s, 3 H), 0.12 (s, 3 H), 0.05 (s, 3 H), 0.03 (s, 3 H); 13C NMR
(CDCl3, 75 MHz) δ 161.2, 137.0, 129.0, 128.1, 126.4, 102.3,
96.5, 91.2, 81.9, 73.6, 71.6, 68.8, 65.3, 26.0, 26.0, 18.3, 18.0,
-3.43, -4.07, -4.28, -4.51. MS (+APCI) 640 (MH+, 0.6).
Dim er 26a . To diacid 16a 2 (180 mg, 0.228 mmol) was added
a solution of trichloroacetimidate 15 (293 mg, 0.457 mmol) in
4 mL of benzene to produce a suspension. The reaction mixture
was heated at reflux for 18 h, at which time the resulting clear
yellow solution was cooled to room temperature and concen-
trated to a yellow foam. Purification of this residue by flash
column chromatography, eluting with 0-15% EtOAc in hex-
anes, afforded 267 mg (67%) of dimer 26a : IR (CDCl3) 1736
cm-1; 1H NMR (400 MHz, CDCl3) δ 7.51-7.13 (m, 37 H), 7.05
(s, 1 H), 5.90 (d, J ) 6.0 Hz, 1 H), 5.85 (d, J ) 6.0 Hz, 1 H),
5.43 (s, 1 H), 5.39 (s, 1 H), 5.24-4.95 (m, 10 H), 4.30 (dd, J )
10.3, 4.8 Hz, 1 H), 4.20-4.17 (m, 1 H), 3.91 (t, J ) 6.8 Hz, 2
H), 3.85 (t, J ) 6.0 Hz, 2 H), 3.76-3.57 (m, 5 H), 3.49-3.43
(m, 1 H), 0.85 (s, 9 H), 0.81 (s, 9 H), 0.80 (s, 18 H), 0.11 (s, 6
H), 0.08 (s, 3 H), 0.04 (s, 9 H), 0.02 (s, 3 H), 0.00 (s, 3 H); 13C
NMR (100 MHz, CDCl3) δ 164.4, 152.9, 152.8, 149.9, 147.4,
146.5, 143.1, 142.3, 137.7, 137.2, 137.1, 136.7, 136.6, 136.5,
136.2, 128.6, 128.6, 128.5, 128.3, 128.3, 128.2, 128.2, 128.1,
128.1, 128.1, 128.0, 127.9, 127.7, 127.7, 127.5, 126.4, 126.4,
124.3, 119.2, 111.1, 109.9, 109.5, 102.1, 101.7, 95.7, 95.4, 81.6,
81.3, 77.2, 75.8, 75.6, 75.5, 75.2, 74.9, 74.6, 71.5, 71.4, 69.0,
68.8, 65.8, 65.5, 26.0, 25.9, 25.8, 25.8, 18.2, 18.1, 17.9, -3.45,
-3.50, -3.75, -3.90, -4.03, -4.16. MS (+MALDI) 1768
(MNa+), 1784 (MK+). Anal. Calcd for C99H124O20Si4: C, 68.09;
H, 7.16. Found: C, 68.01; H, 7.43.
18.4; MS (+FAB) 1449 (MH+, 100). Anal. Calcd for C77H76O28
:
C, 63.81; H, 5.32. Found: C, 63.79; H, 5.57.
1,2,3,4,6-P en t a -O-(3,4,5-t r i-O-b en zyloxyb en zoyl)-â-D-
glu cop yr a n ose (24). A solution of trichloroacetimidate 229a
(100 mg, 0.050 mmol) in 0.5 mL of toluene was treated with
acid 23 (22 mg, 0.05 mmol), and the resulting reaction mixture
was heated at reflux for 18 h. After cooling to room temper-
ature, the reaction mixture was concentrated and purified by
flash column chromatography, eluting with 10-40% EtOAc
in hexanes, to provide 60 mg (53%) of anomeric ester 24. The
spectral data for this product matched those reported previ-
ously for this compound.19
1-O-(o-Nit r ob e n zyl)-4,6-O-Be n zylid e n e -2,3-b is(t er t -
bu tyld im eth ylsilyl)-â-D-glu cop yr a n osid e. A cooled (0 °C)
solution of diol 25 (1.01 g, 2.50 mmol) in 10 mL of dichlo-
romethane was treated with 2,6-lutidine (1.15 mL, 9.87 mmol)
and tert-butyldimethylsilyl trifluoromethanesulfonate (1.70
mL, 7.40 mmol). The ice bath was removed and the pale yellow
reaction mixture was stirred at room temperature for 4 h and
then diluted with 50 mL of Et2O and quenched with 20 mL of
1 M HCl. The organic layer was separated and washed with
water (20 mL) and brine (20 mL), dried over Na2SO4, filtered,
and concentrated. The residue was purified by flash column
chromatography, eluting with 0-10% EtOAc in hexanes, to
afford 1.48 g (94%) of the bis silyl ether as an oily white solid:
1H NMR (300 MHz, CDCl3) δ 8.11 (dd, J ) 8.3, 1.3 Hz, 1 H),
7.92 (d, J ) 7.9 Hz, 1 H), 7.65 (dt, J ) 7.5, 1.2 Hz, 1 H), 7.48-
7.43 (m, 3 H), 7.37-7.33 (m, 3 H), 5.42 (s, 1 H), 5.27 (d, J )
15.5 Hz, 1 H), 5.04 (d, J ) 15.4 Hz, 1 H), 4.62 (d, J ) 6.0 Hz,
1 H), 4.31-4.27 (m, 1 H), 3.85-3.80 (m, 1 H), 3.70 (t, J ) 6.2
Hz, 1 H), 3.65-3.56 (m, 4 H), 0.88 (s, 9 H), 0.83 (s, 9 H), 0.11
(s, 3 H), 0.08 (s, 3 H), 0.05 (s, 3 H), 0.0 (s, 3 H); 13C NMR (75
MHz, CDCl3) δ 146.8, 137.2, 134.7, 133.6, 129.1, 128.1, 127.9,
126.5, 124.6, 103.1, 102.2, 81.8, 77.2, 75.9, 69.1, 67.7, 65.5, 26.1,
26.1, 18.3, 18.2, -3.29, -3.43, -3.76, -3.87. MS (+APCI) 632
(MH+, 2). Anal. Calcd for C32H49NO8Si2: C, 60.82; H, 7.82; N,
2.22. Found: C, 60.93; H, 7.94; N, 2.15.
4,6-O-Ben zylid en e-2,3-b is(ter t-b u t yld im et h ylsilyl)-D-
glu cop yr a n ose. A 100-mL Pyrex tube was charged with a
solution of 1-O-(o-nitrobenzyl)-4,6-O-Benzylidene-2,3-bis(tert-
butyldimethylsilyl)-â-D-glucopyranoside (404 mg, 0.639 mmol)
in 30 mL of THF, 30 mL of absolute ethanol, and 6 mL of
water. The solution was purged with argon for 10 min. The
tube was sealed with a rubber septum and immersed in a
Rayonet photochemical apparatus. Irradiation at 350 nm for
10 h at room temperature afforded a dark orange-red oil after
concentration. Purification of the residue by flash column
chromatography, eluting with 5-15% EtOAc in hexanes,
provided 0.281 g (88%) of the alcohol as a sticky yellow foam
(ca. 80:20 mixture of R/â anomers): IR (CDCl3): 3600, 3563,
Tetr a ol 26b. A solution of dimer 26a (263 mg, 0.151 mmol)
in 4 mL of THF at room temperature was treated with acetic
acid (0.052 mL, 0.908 mmol) and n-Bu4NF (1 M in THF, 1.35
mL, 1.35 mmol). The resulting light yellow reaction mixture
was stirred at room temperature for 7 h and then diluted with
30 mL of EtOAc and poured over 10 mL of 1 M H3PO4. The
organic phase was washed with water (10 mL) and brine (10
mL), dried over Na2SO4, filtered and concentrated to provide
a yellow foam. Purification of the residue by flash column
chromatography, eluting with 20-50% EtOAc in hexanes, gave
146 mg (75%) of tetraol 26b: IR (CDCl3) 3591, 3475 (br), 1733
cm-1; 1H NMR (400 MHz, CDCl3) δ 7.46-7.06 (m, 37 H), 7.01
(d, J ) 1.5 Hz, 1 H), 5.79 (d, J ) 8.1 Hz, 1 H), 5.62 (d, J ) 8.1
Hz, 1 H), 5.48 (s, 1 H), 5.39 (s, 1 H), 5.14 (s, 5 H), 5.08-4.86
(m, 5 H), 4.33 (dd, J ) 10.3, 4.5 Hz, 1 H), 4.23 (dd, J ) 10.2,
4.5 Hz, 1 H), 3.85 (t, J ) 9.0 Hz, 1 H), 3.73-3.66 (m, 3 H),
1
2955 cm-1; H NMR (360 MHz, CDCl3) δ 7.47-7.45 (m, 4 H,
R,â), 7.36-7.25 (m, 6 H, R,â), 5.44 (s, 1 H, R), 5.43 (s, 1 H, â),
5.14 (dd, J ) 2.0, 1.3 Hz, 1 H, R), 4.67 (t, J ) 6.6 Hz, 1 H, â),
4.29 (dd, J ) 10.3, 4.8 Hz, 1 H, R), 4.32-4.26 (m, 1 H, â), 4.06
(dt, J ) 10.0, 5.0 Hz, 1 H, R), 3.95 (t, J ) 8.7 Hz, 1 H, R),
(19) Khanbabaee, K.; Lo¨tzerich, K. Tetrahedron 1997, 53, 10725.

8018 J . Org. Chem., Vol. 65, No. 23, 2000
Feldman et al.
3.58-3.45 (m, 6 H), 3.32 (t, J ) 9.2 Hz, 1 H), 3.09-3.06 (m, 1
H), 2.97-2.89 (m, 2 H); 13C NMR (75 MHz, CDCl3) δ 164.3,
164.1, 152.8, 152.5, 150.1, 147.4, 146.5, 142.4, 142.3, 137.3,
136.9, 136.7, 136.6, 136.3, 136.1, 129.3, 129.2, 128.6, 128.6,
128.5, 128.4, 128.2, 128.2, 128.1, 128.0, 127.8, 127.6, 126.4,
126.3, 123.8, 119.2, 111.0, 110.0, 109.7, 101.9, 101.7, 94.7, 94.6,
80.0, 79.8, 77.2, 76.8, 75.7, 75.6, 75.5, 73.5, 73.3, 73.0, 71.3,
68.3, 68.2, 66.9, 66.8. MS (+MALDI) 1311 (MNa+), 1327 (MK+).
Anal. Calcd for C75H68O20: C, 69.87; H, 5.32. Found: C, 69.49;
H, 5.63.
yellow foam. The crude product dissolved in Et2O was filtered
again through Celite to remove residual DCU and purified by
flash column chromatography, eluting with 10-30% EtOAc
in hexanes, to furnish 271 mg (87%) of 28a as a white foam:
IR (CDCl3) 1731 cm-1 1H NMR (360 MHz, CDCl3) δ 7.54-
;
6.98 (m, 128 H), 6.03 (d, J ) 8.0 Hz, 1 H), 5.99 (d, J ) 8.0 Hz,
1 H), 5.94-5.87 (m, 2 H), 5.82-5.71 (m, 4 H), 5.20-4.76 (m,
34 H), 4.57-4.49 (m, 2 H), 4.33-4.30 (m, 2 H), 4.17-4.10 (m,
2 H), 0.97 (s, 9 H), 0.96 (s, 18 H), 0.93 (s, 9 H), 0.18 (s, 3 H),
0.17 (s, 3 H), 0.15 (s, 3 H), 0.15 (s, 3 H), 0.12 (s, 6 H), 0.10 (s,
6 H); 13C NMR (90 MHz, CDCl3) δ 165.4, 165.3, 165.2, 165.2,
165.0, 164.1, 164.1, 163.8, 161.0, 152.6, 152.6, 152.5, 152.4,
149.7, 148.5, 148.5, 148.4, 147.5, 146.2, 143.9, 143.1, 143.0,
142.8, 142.5, 141.9, 141.9, 141.6, 139.9, 139.8, 139.6, 138.6,
138.5, 137.6, 137.4, 136.7, 136.6, 136.4, 136.3, 129.2, 129.1,
128.6, 128.5, 128.4, 128.3, 128.2, 128.1, 128.1, 128.0, 128.0,
127.9, 127.9, 127.8, 127.7, 127.7, 127.6, 127.5, 127.5, 126.2,
123.9, 123.8, 123.7, 123.6, 123.5, 123.2, 122.5, 118.9, 118.9,
118.3, 118.1, 117.5, 110.6, 110.3, 109.8, 109.1, 109.1, 104.2,
104.1, 92.8, 92.5, 77.2, 75.5, 75.1, 75.0, 73.2, 71.6, 71.4, 71.2,
71.0, 70.9, 68.0, 67.8, 61.7, 61.5, 25.6, 25.5, 18.3, 18.2, 18.2,
-4.50, -4.56; MS (+FAB) 4523 (MH+). Anal. Calcd for
Hexa ester 26c. A mixture of acid 23 (183 mg, 0.415 mmol),
DMAP (15 mg, 0.123 mmol), and DMAP•HCl (20 mg, 0.126
mmol) was treated with a solution of tetraol 26b (134 mg,
0.104 mmol) in 4 mL of CH2Cl2. To this suspension was added
DCC (107 mg, 0.519 mmol) at room temperature, and the
resulting cloudy reaction mixture was stirred for 19 h. After
being cooled at -18 °C for 30 min, the reaction mixture was
filtered through Celite, washing with several portions of Et2O.
The filtrates were washed with 1 N HCl (15 mL), water (10
mL), and brine (10 mL), dried over Na2SO4, filtered, and
concentrated to provide a yellow foam. The crude product
dissolved in Et2O was filtered again through Celite to remove
residual DCU and purified by flash column chromatography,
eluting with 10-30% EtOAc in hexanes, to furnish 300 mg
C
277H252O52Si4: C, 73.52; H, 5.61. Found: C, 73.29; H, 5.85.
Tetr a p h en ol 28b. A solution of tetrakis(silyl ether) 28a
(97%) of hexaester 26c: IR (CDCl3) 1731 cm-1
;
1H NMR
(251 mg, 0.055 mmol) in 4 mL of THF was treated with acetic
acid (0.019 mL, 0.33 mmol) and n-Bu4NF (1 M in THF, 0.335
mL, 0.335 mmol) at room temperature. The pale yellow
reaction mixture was stirred for 1 h, diluted with 50 mL of
EtOAc, and poured over 20 mL of 1 M H3PO4. The organic
phase was washed with water (15 mL) and brine (15 mL), dried
over Na2SO4, filtered and concentrated. Purification by flash
column chromatography, eluting with 30-50% EtOAc in
hexanes, provided 196 mg (87%) of 28b as a white solid: IR
(CDCl3) 3574, 3416 (br), 1731 cm-1; 1H NMR (400 MHz, CDCl3)
δ 7.54-6.99 (m, 128 H), 6.03 (d, J ) 7.3 Hz, 1 H), 6.01 (d, J )
7.8 Hz, 1 H), 5.87 (t, J ) 9.7 Hz, 1 H), 5.84 (t, J ) 9.7 Hz, 1
H), 5.74-5.62 (m, 4 H), 5.28-4.86 (m, 34 H), 4.52-4.49 (m, 2
H), 4.38-4.36 (m, 1 H), 4.28-4.26 (m, 1 H), 4.19-4.11 (m, 2
H); 13C NMR (90 MHz, CDCl3) δ 165.8, 165.6, 165.5, 165.1,
165.0, 164.4, 164.3, 164.1, 161.5, 152.6, 152.4, 149.8, 148.4,
148.3, 147.5, 146.4, 143.5, 143.1, 143.0, 142.8, 142.4, 139.5,
139.2, 139.0, 138.7, 138.6, 138.4, 137.5, 137.4, 137.3, 136.7,
136.5, 136.4, 136.2, 129.4, 129.2, 128.6, 128.5, 128.5, 128.4,
128.3, 128.2, 128.1, 128.1, 128.0, 127.9, 127.9, 127.8, 127.7,
127.6, 127.5, 126.3, 126.3, 126.2, 123.7, 123.7, 123.6, 123.5,
123.3, 122.8, 122.7, 119.0, 118.9, 118.5, 118.5, 117.6, 114.3,
110.7, 109.9, 109.8, 109.7, 109.2, 109.1, 103.6, 103.5, 92.9, 92.5,
77.2, 75.7, 75.5, 75.2, 75.1, 75.0, 73.3, 73.1, 71.5, 71.2, 71.0,
70.9, 68.7, 68.6, 62.7, 62.3; MS (+FAB) 4068 (MH+). Anal.
Calcd for C253H196O52: C, 74.69; H, 4.86. Found: C, 74.30; H,
5.12.
Cor ia r iin A (1). To a cooled (-40 °C) solution of tetraphenol
28b (177 mg, 0.044 mmol) and pyridine (0.028 mL, 0.35 mmol)
in 7 mL of CH2Cl2 was added a solution of lead tetraacetate
(42 mg, 0.095 mmol) in 2 mL of CH2Cl2, dropwise via syringe
pump over 45 min. The resulting cloudy light orange reaction
mixture was stirred at -35 °C for 75 min, and then poured
into 20 mL of saturated aqueous NaHCO3 and extracted with
75 mL of EtOAc. The organic phase was washed with 1 M H3-
PO4 (20 mL) and brine (20 mL), dried over Na2SO4, filtered,
and concentrated to afford a light orange oil. Purification of
the residue by flash column chromatography, eluting with 20-
50% EtOAc in hexanes, furnished 131 mg (74%) of HHDP-
containing dimeric ellagitannin as a complex mixture of
regioisomers. The identity of the products was verified by
inspection of the 1H NMR spectrum, which contains diagnostic
HHDP singlets from 6.78 to 6.70 ppm. The HHDP-containing
products (122 mg, 0.03 mmol) were dissolved in 5 mL of THF
and treated with 10% Pd/C (40 mg, 33 wt % of starting
material). The system was purged several times with hydrogen
and stirred under a balloon of hydrogen for 48 h. The reaction
mixture was then purged with Ar and filtered through Celite,
washing with acetone. Complete deprotection required repeti-
tion of this process two times with fresh catalyst (22 and 18
mg of Pd/C, 4 mL of THF, 24 h each). Final concentration of
(CDCl3) δ 7.50-6.96 (m, 98 H), 6.00 (d, J ) 8.2 Hz, 1 H), 5.98
(d, J ) 9.1 Hz, 1 H), 5.86 (t, J ) 9.6 Hz, 1 H), 5.83 (t, J ) 9.6
Hz, 1 H), 5.68 (t, J ) 8.9 Hz, 2 H), 5.50 (s, 2 H), 5.17-4.89 (m,
34 H), 4.44-4.31 (m, 2 H), 3.91 (t, J ) 8.9 Hz, 2 H), 3.83-3.76
(m, 4 H); 13C NMR (90 MHz, CDCl3) δ 165.2, 165.1, 163.9,
161.3, 152.7, 152.6, 152.5, 152.5, 149.9, 147.6, 146.4, 143.5,
143.1, 142.9, 142.8, 142.6, 137.7, 137.3, 136.7, 136.6, 136.5,
136.4, 136.1, 129.1, 128.7, 128.6, 128.5, 128.5, 128.4, 128.3,
128.3, 128.3, 128.2, 128.1, 128.1, 128.0, 127.9, 127.8, 127.6,
127.5, 127.5, 126.2, 124.2, 123.6, 123.6, 123.1, 117.6, 110.7,
109.8, 109.6, 109.3, 109.2, 109.2, 101.6, 93.3, 92.9, 78.4, 77.2,
75.6, 75.5, 75.2, 75.1, 72.1, 72.0, 71.9, 71.8, 71.2, 71.0, 71.0,
68.3, 67.4, 67.3; MS (+MALDI) 3002 (MNa+). Anal. Calcd for
C
187H156O36: C, 75.39; H, 5.28. Found: C, 75.38; H, 5.30.
Tetr a ol 32. To a solution of the hexaester 26c (288 mg,
0.097 mmol) in 10 mL of CH2Cl2/methanol (1:1) was added
iodine (61 mg, 0.240 mmol). The dark brown reaction mixture
was heated at reflux (sand bath 45-50 °C) for 42 h. After
cooling to room temperature, the reaction mixture was diluted
with 30 mL of EtOAc and washed with 10% aqueous Na2S2O3,
water, and brine (15 mL each). The organic phase was dried
over Na2SO4, filtered, and concentrated to afford a white oily
solid. Purification of the residue by flash column chromatog-
raphy, eluting with 30-50% EtOAc in hexanes and then 5:95
methanol/50% EtOAc in hexanes, provided 208 mg (77%) of
tetraol 32 as a white solid: IR (CDCl3) 3601, 3452 (br), 1730
cm-1; 1H NMR (400 MHz, CDCl3) δ 7.46-6.94 (m, 88 H), 5.95
(d, J ) 8.2 Hz, 2 H), 5.68 (t, J ) 9.0 Hz, 1 H), 5.56 (t, J ) 9.0
Hz, 1 H), 5.41 (t, J ) 9.4 Hz, 1 H), 5.38 (t, J ) 9.6 Hz, 1 H),
5.12-4.80 (m, 34 H), 4.03-3.97 (m, 3 H), 3.85-3.72 (m, 4 H),
3.62-3.60 (m, 1 H), 3.32 (d, J ) 3.5 Hz, 1 H), 3.29 (d, J ) 3.8
Hz, 1 H); 13C NMR (75 MHz, CDCl3) δ 167.1, 167.0, 165.1,
164.2, 152.8, 152.6, 152.5, 152.5, 152.3, 149.8, 147.6, 146.5,
143.3, 143.2, 143.1, 143.0, 142.8, 137.7, 137.3, 136.7, 136.4,
136.4, 136.3, 136.1, 128.7, 128.6, 128.5, 128.4, 128.3, 128.1,
128.1, 128.1, 127.9, 127.7, 127.6, 127.6, 127.5, 123.6, 123.0,
117.8, 110.4, 109.5, 109.3, 109.1, 92.8, 92.2, 77.2, 75.8, 75.5,
75.1, 71.1, 71.0, 71.0, 69.1, 68.8, 61.5, 61.3; MS (-FAB) 2801
(M+, 13). Anal. Calcd for C173H148O36
Found: C, 73.95; H, 5.38.
: C, 74.13; H, 5.32.
Deca ester 28a . A mixture of acid 27 (123 mg, 0.274 mmol),
DMAP (8.5 mg, 0.070 mmol), and DMAP•HCl (11 mg, 0.069
mmol) was treated with a solution of tetraol 32 (192 mg, 0.068
mmol) in 3 mL of CH2Cl2. To this suspension was added DCC
(71 mg, 0.344 mmol) at room temperature, and the resulting
cloudy reaction mixture was stirred for 23 h. After being cooled
at -18 °C for 30 min, the reaction mixture was filtered through
Celite, washing with several portions of Et2O. The filtrates
were washed with 1 N HCl, water, and brine (15 mL each),
dried over Na2SO4, filtered and concentrated to provide a

Ellagitannin Chemistry
J . Org. Chem., Vol. 65, No. 23, 2000 8019
the filtrates provided a gray-green oily solid which was
triturated with three portions each of Et2O and hexanes and
dried to provide 45 mg (80%) of coriariin A 1 as a gray-green
solid: 1H NMR (400 MHz, acetone-d6 + D2O) δ 7.24 (d, J )
1.8 Hz, 1 H), 7.16 (s, 1 H), 7.00 (s, 2 H), 6.99 (s, 2 H), 6.95 (s,
2 H), 6.95 (s, 2 H), 6.67 (d, J ) 2.0 Hz, 1 H), 6.65 (s, 1 H), 6.62
(s, 1 H), 6.46 (s, 2 H), 6.09 (d, J ) 8.2 Hz, 1 H), 6.02 (d, J )
8.4 Hz, 1 H), 5.79 (t, J ) 9.8 Hz, 1 H), 5.76 (t, J ) 9.8 Hz, 1
H), 5.55 (dd, J ) 8.4, 6.0 Hz, 1 H), 5.53 (dd, J ) 8.5, 6.0 Hz,
1 H), 5.32-5.25 (m, 2 H), 5.17 (t, J ) 9.0 Hz, 1 H), 5.15 (t, J
) 9.1 Hz, 1 H), 4.50-4.41 (m, 2 H), 3.81 (d, J ) 13.2 Hz, 1 H),
72.3, 70.8, 63.6, 63.1, 26.1, 25.9, 25.9, 25.8, 25.7, 18.3, 18.0,
18.0, 17.9, 17.8, -4.2, -4.3, -4.4, -4.4, -4.5, -4.6, -4.8, -4.8,
-4.9, -5.0, -5.0, -5.1, -5.3; MS (+APCI) 659 (MNa+, 6).
Mod el Dim er 11. A mixture of acid 23 (35 mg, 0.079 mmol),
DMAP (2.5 mg, 0.020 mmol), and DMAP‚HCl (3.0 mg, 0.019
mmol) was treated with a solution of tetraol 32 (55 mg, 0.02
mmol) in 1.25 mL of CH2Cl2. To this suspension was added
DCC (20 mg, 0.097 mmol) at room temperature, and the
resulting cloudy reaction mixture was stirred for 15 h. After
cooling at -18 °C for 30 min, the reaction mixture was filtered
through Celite, washing with several portions of Et2O. The
filtrates were washed with 1 N HCl, water, and brine (5 mL
of each), dried over Na2SO4, filtered and concentrated to
provide a light yellow foam. The crude product dissolved in
Et2O was filtered again through Celite using cold Et2O to
remove residual DCU and purified by flash column chroma-
tography, eluting with 10-40% EtOAc in hexanes, to provide
84 mg of the decaester, still contaminated with some DCU.
Filtration through Celite using cold Et2O furnished 78 mg
3.76 (d, J ) 13.1 Hz, 1 H); 13C NMR (90 MHz, acetone-d6
+
D2O, dioxane (67.4) as internal standard) δ 168.0, 167.9, 167.5,
166.2, 165.6, 164.7, 162.0, 161.6, 147.8, 146.3, 145.7, 145.7,
145.6, 145.0, 145.0, 144.3, 143.2, 141.0, 140.7, 140.3, 139.2,
139.1, 139.1, 138.9, 136.3, 136.2, 129.5, 129.1, 129.1, 129.0,
126.6, 126.3, 125.7, 125.7, 120.3, 120.2, 120.2, 120.1, 115.6,
115.5, 112.2, 112.1, 110.1, 110.0, 109.9, 108.1, 108.0, 107.6,
93.5, 93.1, 73.1, 73.0, 72.8, 72.8, 71.5, 71.5, 70.5, 70.5, 62.9,
62.8. CD (MeOH) 231 nm, +42.7, 260 nm, -3.8, 281 nm, +10.9;
HRMS (+FAB) calcd for C82H59O52 (MH+) 1875.1972, found
1875.1937.
1
(89%) of product as a white foam: IR (CDCl3) 1731 cm-1; H
NMR (400 MHz, CDCl3) δ 7.51-7.13 (m, 158 H), 7.05-6.97
(m, 6 H), 6.10 (t, J ) 8.2 Hz, 2 H), 6.01 (t, J ) 9.8 Hz, 1 H),
5.99 (t, J ) 9.7 Hz, 1 H), 5.82-5.73 (m, 4 H), 5.14-4.83 (m,
58 H), 4.75-4.69 (m, 2 H), 4.34-4.27 (m, 4 H); 13C NMR (90
MHz, CDCl3) δ 165.6, 165.4, 165.4, 165.1, 164.9, 164.9, 163.9,
161.2, 152.7, 152.6, 152.6, 152.5, 152.3, 149.7, 147.6, 146.3,
143.9, 143.2, 143.1, 143.0, 142.7, 142.6, 142.5, 137.6, 137.5,
137.5, 137.4, 137.3, 137.3, 136.6, 136.6, 136.5, 136.4, 136.3,
136.3, 136.3, 136.2, 128.7, 128.5, 128.5, 128.4, 128.3, 128.3,
128.2, 128.1, 127.9, 127.8, 127.7, 127.7, 127.5, 124.5, 124.5,
123.7, 123.6, 123.1, 110.6, 110.3, 109.8, 109.2, 109.2, 92.9, 92.6,
77.2, 75.5, 75.1, 75.0, 73.3, 73.3, 72.7, 72.6, 71.4, 71.3, 71.2,
71.1, 71.0, 70.9, 69.8, 69.7, 63.0, 62.9; MS (+FAB) 4493 (MH+,
10). Anal. Calcd for C235H236O52: C, 76.19; H, 5.29. Found: C,
76.04; H, 5.30.
A solution of the perbenzylated model dimer (39 mg, 0.009
mmol) in 2 mL of THF was treated with 10% Pd/C (10 mg, 25
wt % of starting material). The system was purged several
times with hydrogen and stirred under a balloon of hydrogen
for 36 h. The reaction mixture was then purged with Ar and
filtered through Celite, washing with acetone. Concentration
of the filtrates provided a gray oily solid which was triturated
with two portions each of dichloromethane and hexanes and
dried to afford 17 mg (99%) of gallotannin dimer 11 as a light
gray solid: 1H NMR (400 MHz, acetone-d6) δ 7.22 (d, J ) 2.0
Hz, 1 H), 7.17 (s, 2 H), 7.13 (s, 2 H), 7.10 (s, 1 H), 7.03 (s, 2 H),
7.01 (s, 2 H), 7.00 (s, 2 H), 7.00 (s, 2 H), 6.95 (s, 2 H), 6.93 (s,
2 H), 6.73 (d, J ) 1.9 Hz, 1 H), 6.21 (d, J ) 8.3 Hz, 1 H), 6.13
(d, J ) 8.3 Hz, 1 H), 5.97 (t, J ) 9.5 Hz, 1 H), 5.92 (t, J ) 9.6
Hz, 1 H), 5.62 (t, J ) 9.7 Hz, 1 H), 5.60 (t, J ) 9.7 Hz, 1 H),
5.54 (t, J ) 9.1 Hz, 2 H), 4.50-4.43 (m, 4 H), 4.39-4.35 (m, 2
H); 13C NMR (90 MHz, acetone-d6) δ 166.8, 166.8, 166.2, 166.2,
166.0, 166.0, 165.9, 165.2, 162.6, 148.3, 146.8, 146.3, 146.3,
146.2, 143.8, 141.5, 141.5, 140.9, 139.7, 139.7, 139.6, 139.6,
139.5, 139.4, 139.4, 138.1, 121.8, 121.7, 121.0, 120.9, 120.9,
120.8, 119.7, 113.5, 112.7, 110.6, 110.6, 110.5, 110.2, 108.5,
93.7, 93.4, 74.3, 74.1, 73.8, 73.7, 73.7, 73.6, 72.0, 71.9, 69.6,
69.4, 63.3, 62.9; HRMS (+FAB) calcd for C82H63O52 (MH+)
1879.2285, found 1879.2308.
1-O-(o-Nit r ob e n zyl)-2,3,4,6-t e t r a k is-O-(t er t -b u t yld i-
m eth ylsilyl)-â-D-glu cop yr a n osid e. A suspension of tetraol
2913 (756 mg, 2.40 mmol) in 12 mL of CH2Cl2 was treated with
2,6-lutidine (2.25 mL, 19.3 mmol) and cooled at 0 °C. To the
resulting pale yellow solution was added tert-butyldimethyl-
silyl trifluoromethanesulfonate (3.30 mL, 14.4 mmol). The ice
bath was removed, and the reaction mixture was stirred at
room temperature for 3 h and then diluted with 100 mL of
Et2O and poured into 1 N HCl. The organic layer was
separated and washed with water (30 mL) and brine (30 mL),
dried over Na2SO4, filtered, and concentrated to afford a light
orange oil. The crude product was purified by flash column
chromatography, eluting with 0-10% EtOAc in hexanes, to
furnish 1.83 g (99%) of the tetrakis(silyl ether) as a pale yellow
oil: 1H NMR (360 MHz, CDCl3) δ 8.10 (d, J ) 8.2 Hz, 1 H),
7.97 (d, J ) 7.9 Hz, 1 H), 7.64 (t, J ) 7.5 Hz, 1 H), 7.42 (t, J
) 7.5 Hz, 1 H), 5.35 (d, J ) 15.7 Hz, 1 H), 4.95 (d, J ) 16.1
Hz, 1 H), 4.92 (d, J ) 6.5 Hz, 1 H), 3.98 (d, J ) 2.6 Hz, 1 H),
3.89-3.83 (m, 1 H), 3.83 (d, J ) 3.2 Hz, 1 H), 3.79-3.70 (m, 3
H), 0.91 (s, 9 H), 0.90 (s, 9 H), 0.88 (s, 9 H), 0.85 (s, 9 H), 0.13,
0.11, 0.09, 0.09, 0.03 (all s, 24 H total); 13C NMR (90 MHz,
CDCl3) δ 146.7, 135.3, 133.6, 128.9, 127.5, 124.5, 101.6, 82.3,
79.0, 77.6, 70.0, 67.2, 64.0, 26.1, 25.7, 18.3, 18.3, 18.0, 17.9,
-4.3, -4.3, -4.5, -4.6, -4.7, -4.8, -5.3, -5.4; MS (+APCI)
794 (MNa+, 15).
2,3,4,6-Tetr a k is-O-(ter t-bu tyld im eth ylsilyl)-D-glu cop y-
r a n ose (30). A solution of 1-O-(o-nitrobenzyl)-2,3,4,6-tetrakis-
O-(tert-butyldimethylsilyl)-â-D-glucopyranoside (418 mg, 0.541
mmol) in 30 mL of THF, 30 mL of absolute ethanol, and 6 mL
of water was prepared in a 100-mL Pyrex tube and purged
with Ar for 10 min. The tube was sealed with a rubber septum
and placed in a Rayonet photochemical apparatus. Irradiation
at 350 nm for 9 h at room temperature afforded a dark orange
reaction mixture which was concentrated, using several ben-
zene washes to remove water. The resulting dark orange-red
oil was purified by flash column chromatography, eluting with
0-5% EtOAc in hexanes, to provide 247 mg (72%) of alcohol
30 as a ca. 75:25 mixture of unassigned R/â anomers: IR (thin
film) 3427 (br) cm-1; 1H NMR (400 MHz, CDCl3) δ 5.07 (dd, J
) 11.8, 4.4 Hz, 1 H), 5.01 (dd, J ) 9.2, 3.5 Hz, 1 H), 4.31 (d, J
) 11.9 Hz, 1 H), 3.96-3.65 (m, 12 H), 3.12 (d, J ) 9.2 Hz, 1
H), 0.93, 0.90, 0.89, 0.89, 0.88 (all s, 72 H total), 0.13, 0.12,
0.12, 0.11, 0.10, 0.10, 0.08, 0.06 (all s, 48 H total); 13C NMR
(75 MHz, CDCl3) δ 96.4, 89.9, 78.4, 78.0, 77.2, 76.0, 75.9, 75.0,
Ack n ow led gm en t. We thank the National Insti-
tutes of Health for support of this work through
GM35727.
J O0010936