Comparing n-pentenyl orthoesters and n-pentenyl glycosides as alternative glycosyl donors

Article abstract of DOI:10.1016/S0040-4020(02)00671-3

As is well known, cyclic 1,2-glycosyl orthoesters undergo ready acid catalyzed rearrangement to 2-O-acyl glycosides in which the alkoxy group is transferred from the orthoester to the anomeric center in a highly stereocontrolled process. The related n-pentenyl derivatives are unique in that either the orthoester (NPOE) or its rearrangement product (NPG_AC) can function as a glycosyl donor, and mechanistic considerations indicate that both should (or could!) lead to the same product(s) arising from trans-orthoesterification, glycosidation, glycosyl esterification, etc. Experiments are described which show that the product obtained from a given reaction can be optimized by careful choice of the donor, NPOE or related NPG_AC, and careful attention to reaction conditions, electrophilic promoter, 'size' of the glycosyl acceptor, and experimental protocol.

Full text of DOI:10.1016/S0040-4020(02)00671-3

Tetrahedron 58 (2002) 7345–7354
Comparing n-pentenyl orthoesters and n-pentenyl glycosides as
alternative glycosyl donors
b
Mateusz Mach,a Urs Schlueter,a Felix Mathew,a Bert Fraser-Reida and Kevin C. Hazen
,
*
aNatural Products and Glycotechnology Research Institute, Inc., 4118 Swarthmore Road, Durham, NC 27707, USA
bDepartments of Pathology and Microbiology, University of Virginia Health System, Charlottesville, VA 22908, USA
Received 23 April 2002; accepted 17 June 2002
Abstract—As is well known, cyclic 1,2-glycosyl orthoesters undergo ready acid catalyzed rearrangement to 2-O-acyl glycosides in which
the alkoxy group is transferred from the orthoester to the anomeric center in a highly stereocontrolled process. The related n-pentenyl
derivatives are unique in that either the orthoester (NPOE) or its rearrangement product (NPGAC) can function as a glycosyl donor, and
mechanistic considerations indicate that both should (or could!) lead to the same product(s) arising from trans-orthoesterification,
glycosidation, glycosyl esterification, etc. Experiments are described which show that the product obtained from a given reaction can be
optimized by careful choice of the donor, NPOE or related NPGAC, and careful attention to reaction conditions, electrophilic promoter, ‘size’
of the glycosyl acceptor, and experimental protocol. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
n-pentenyloxy residue to electrophilic attack provides
alternative pathways from NPOE 5 and NPGAC 7 to
intermediate 6 via the furanylium ions 8 and 9,
respectively.14 The advantage of the latter pathways is
that the ejected species is the non-nucleophilic halomethyl-
furan 10, which cannot compete with the added alcohol,
SugOH, present in the medium to hamper formation of
coupling product(s) e.g. 11.
Recent publications from several laboratories have focused
attention on the value of glycosyl 1,2-orthoesters such as 1,
for oligosaccharide synthesis.1–4 This interest grows out of
the knowledge that orthoesters typically undergo facile acid
catalyzed rearrangement, wherein the alkoxy group is
transferred to the anomeric center resulting in the formation
of glycosidic products such as 2.5–7 The process is highly
stereoselective and, the OR group so transferred can be a
simple alcohol or a complex sugar.8 In this context, a recent
study by Wang and Kong reported great improvements in
the efficiency of the rearrangement for cases in which the
migrating entity is an oligosaccharide.1
However, as indicated in Scheme 2, the crucial intermediate
6, can also be captured by the alcohol at the site of highest
electron deficiency, to give the trans-orthoesterification
product, 12.13 The potential of this pathway needs to be
examined since (a) it provides an alternative route to 11 via
acid catalyzed rearrangement, and (b) it is usually the major
reaction pathway for uronate glycosyl donors.15 Notably,
this trend is minimized with trichloroacetimidate donors.16
With regard to the orthoesters themselves, Allen and Fraser-
Reid have reported that the classical procedure for their
preparation from 2-O-acyl glycosyl bromides,9,10 3, can be
greatly improved by the addition of tetra n-butyl ammonium
iodide.4 A recent report from Hecht’s laboratory on the use
of ketene acetals, for example 4, as precursors for 1
(R¼CH3) is an important new contribution (Scheme 1).2
Our interest centers upon the unique relationship between an
n-pentenyl orthoester (NPOE) and the corresponding 2-O-
acyl n-pentenyl glycoside (NPGAC), such as 5 and 7,
respectively.11 The standard acid catalyzed rearrangement
presumably follows the pathway 5!6!7,12,13 in which the
pentenyloxy group is transferred from the orthoester to
the anomeric center. However, the susceptibility of the
Keywords: oligosaccharide; glycosyl donors; substrates.
*
Corresponding author. Tel./fax: þ1-919-493-6113;
e-mail: dglucose@aol.com
Scheme 1.
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00671-3

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M. Mach et al. / Tetrahedron 58 (2002) 7345–7354
Scheme 2.
Intermediate 6 is also a good scavenger for water with
production of an orthoacid, e.g. 13, an unstable compound
that is prone to rearrangement to an hydroxy ester. The
seminal investigations of King17 established that
the rearrangement is stereoelectronically driven18
favoring the axially oriented ester on cyclohexyl scaffolds.
On this basis, a manno orthoacid should give 2-O-acyl-
mannose, such as 14, where a gluco analog of 13 should
give a glucosyl ester, such as 15. Indeed, 2-hydroxy
glucosyl acetates had been identified as early as 1930, as
products from reactions of tetra-O-acetyl glucosyl
bromide.19,20
From the network of intermediates shown in Scheme 2, it is
seen that there are major opportunities for inter- or
counterplay between various reacting species. Indeed, the
annoying occurrence of unwanted side products in ortho-
ester reactions,12a indicated the need for close scrutiny of
Scheme 3. (i) PhCOCl, pyridine, DMAP; CH2Cl2; (ii) Ac2O, 30% HBr-AcOH(,85%); (iii) CH2Cl2, 2,6-lutidine, R0-OH or 4-pentenol, Bu4NI; (iv) NaOMe,
MeOH (89%); (v) NaH, PhCH2Br, DMF (84%).

M. Mach et al. / Tetrahedron 58 (2002) 7345–7354
7347
the presumed equivalence of donors such as 5 and 7, and we
report some of our results herein.
(J¼3.0 Hz). Upon acetylation, the doublet shifted to
6.56 ppm (J¼3.6 Hz), while a low field double doublet
appeared at 5.16 ppm (J¼3.6, 10.3 Hz), consistent with H-1
and H-2, respectively, of 22b.
2. Results and discussion
As with the manno analogue in Scheme 4(a), the
rearrangement became virtually quantitative when a small
amount of pent-4-enol was added, NPGAC 24 being
obtained in 97% yield (Scheme 4(b), iv)).
2.1. Preparation of substrates
The substrates for these investigations were obtained as
outlined in Scheme 3. Thus, 3,4,6-tri-O-benzyl-b-D-manno-
pyranose 1,2-(pent-4-enyl orthobenzoate) 17c was prepared
by the more condensed route summarized in Scheme 3(a),
which avoided excessive purification of intermediates as
was done in the previously described procedure.11 This
updated protocol was utilized for the manno 1,2-(benzyl
orthobenzoate) analogue, 18c, as well as for the a-D-
glucopyranose counterpart 20c (Scheme 3(b)). In the latter
case, the five step conversion of D-glucose into the NPOE
triol 20b could be accomplished in 71% overall yield.
The conclusion from the studies in Scheme 4 is that manno
NPOEs undergo acid catalyzed rearrangements in a
straightforward way, while with gluco NPOEs, there can
be problems depending on the conditions used.
2.3. Oxidative hydrolysis of NPOE and NPGAC: donors
According to Scheme 2, key intermediate 6, can be obtained
either from 5 or 7. An NPOE and its trans NPGAC
counterpart should therefore give the same hydrolysis
product(s). That they do not is evident from the studies
summarized in Scheme 5a. Thus, oxidative hydrolysis of
the disarmed NPGAC 24, gave ONLY the 2-O-benzoyl
glucose 23a as a (4:1) a/b mixture in 92% yield. The
material was directly acetylated, and although the mixture of
anomeric acetates, 23b, could not be separated by
chromatography, the a and b anomers could be assigned
2.2. Acid catalyzed rearrangement of glycosyl
orthoesters
Rearrangement of the orthoesters to give the corresponding
alkyl 2-O-benzoyl glycosides was studied carefully, begin-
ning with the manno NPOE 17c. Use of ‘standard’
conditions11 (CH2Cl2/CAS/reflux) required 5 h whereas
with TESOTf, the rearrangement was complete in ,5 min
at room temperature to give 21a in ,80% yield (Scheme
4(a), i). Significantly addition of 5–10 mol% of the
appropriate alcohol raised the yield of the rearrangement
product 21a or b to 95% (Scheme 4(a), ii)).
1
on the basis of characteristic H NMR signals for H-1 and
1
H-2. Thus, the H NMR spectrum showed a doublet at
6.44 ppm (J¼3.6 Hz) along with a higher-field double-
doublet at 5.32 ppm (J¼3.6, 10.2 Hz) consistent with H-1
and H-2 of 23ba. The corresponding signals for 23bb
appeared at 5.79 ppm (J¼8.1 Hz) and 5.40 ppm (J¼8.1,
8.7 Hz).
With the gluco NPOE 20c, a rapid reaction occurred (2 min)
to give the desired n-pentenyl glycoside (NPGAC) 24, but
contaminated with varying amounts of the glycosyl
benzoate 22a and the hydrolysis product 23a. Compound
22a was identified by the low field doublet at 6.48 ppm
In the case of the gluco NPOE 20c, oxidative hydrolysis
gave a 10:1 mixture of 23a and the already described
glucosyl benzoate, 22a, in 96% overall yield.
Scheme 4.

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M. Mach et al. / Tetrahedron 58 (2002) 7345–7354
Scheme 5. (i) CH3CN, H2O, NBS; (ii) Ac2O, pyridine, DMAP; (iii) CH2Cl2, TBDMSOTf, 2 min.
The manno NPOE 17c gave rise to the 2-O-benzoyl
mannose 25a in 98% yield (Scheme 5(b)) with no evidence
for the mannosyl benzoate (corresponding to 22a) in
keeping with King’s stereoelectronic principle.17 Under
the hydrolysis conditions used, disarmed donor 21a gave the
hydrolysis products 25a, along with bromohydrin 26.14
2.4. Transorthoesterification versus glycosidation
It is evident from Scheme 2 that either of the n-pentenyl
donors (5 or 7) can give rise to an orthoester such as 12, as
well as the desired glycosidic product 11.
Can one or other product be optimized?
As was the case with the acid-catalyzed hydrolyses in
Scheme 4, the oxidative alternative in Scheme 5 is (can be!)
more problematic for gluco NPOEs than for manno.
However, for the NPGAC counterparts, oxidative hydrolysis
of the gluco derivative is more straightforward. The
formation of some bromohydrin 26 is undoubtedly a
reflection of the great stability of mannoside 21a.22
It is well-known that glycosyl orthoesters are best
prepared under non-acidic conditions, and this is in keeping
with their acid lability.12 In this regard, n-pentenyl donors
can be activated under a variety of conditions, acidic (NBS/
Lewis acid), neutral (NBS), or slightly basic3,4 e.g.
iodonium sym-dicollidinium perchlorate (IDCP)23 and
Scheme 6.

M. Mach et al. / Tetrahedron 58 (2002) 7345–7354
7349
trichoromethanesulfonate (IDCT24) promoters. We were
therefore interested to see how NPOEs behaved under these
different conditions.
low, and the chances of scavenging by traces of adventitious
water were reduced.
Thus, the gluco NPOE donor 20c and the benzyl mannoside
acceptor 29, (which was obtained by desterification of
benzoate 21b), were dissolved in methylene chloride.
Portions of the solution were treated with the slightly acidic
and slightly basic reagents, NBS/TESOTf and IDCT,
respectively. The effect of the promoter was clearly
demonstrated since both experiments led to different
coupling products exclusively in virtually the same yields
(Scheme 7(a)), the ‘acidic’ promoter giving disaccharide,
30, and the ‘basic’ promoter the trans-orthoesterification
product 31.
Isopropyl alcohol was chosen as a model acceptor for IDCT
promoted reactions. As indicated in Scheme 6, the gluco and
manno NPOEs 20c and 17c both underwent trans-
orthoesterification to the same extents. That the products
were mixtures of exo and endo isomers of 27 and 28 was
evident from the presence of two CMR signals around
120 ppm in each case.
It was important to determine if the product(s) from NPOE
donors are dependent upon the promoter used, and so we
decided to probe this issue as shown in Scheme 7. In order to
avoid premature reaction of the acid-labile NPOEs, the
protocol was changed from the usual practice3,4 of adding
the promoter to a solution containing the donor and
acceptor, to one in which the acceptor and promoter were
dissolved in methylene chloride, and then the NPOE was
added dropwise as a solution in toluene. In this way, the
concentration of the oxolenium intermediate(s) was kept
Notably, attempts to rearrange orthoester 31 into disacchar-
ide 30 with camphorsulfonic acid were not successful, the
products being the starting benzyl glycoside 29 and the
glycosyl benzoate 22a.
The facile trans-orthoesterification in Scheme 7(a) does not
hold for all glycosyl acceptors as is evident by comparison
Scheme 7.

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M. Mach et al. / Tetrahedron 58 (2002) 7345–7354
with the results in Scheme 7(b). Thus, changing the acceptor
from the monosaccharide 29 to the disaccharide 32,
produced the trisaccharide 33 in 67% yield with no evidence
for the trans-orthoesterification product. The conflicting
results in Schemes 6 and 7 with respect to IDCT as
promoter, make it clear that the ‘size’ of the acceptor may
influence the occurrence of trans-orthoesterification.
3.1. General procedures
Oxidative hydrolysis. The NPOE or corresponding NPGAC
(30 mg, 0.04817 mmol) was dissolved in 5 ml of aceto-
nitrile. Water (0.5 ml) and NBS (26 mg, 1.461 mmol) were
added and the reaction mixture was kept at room
temperature in darkness until TLC (hexanes/ethyl acetate
4:1) indicated the full disappearance of starting material.
The reaction mixture was diluted with ethyl acetate, and
washed with 10% Na2S2O3, water, brine and dried over
sodium sulphate. The products of the reaction were
separated by column chromatography or by preparative
TLC.
The effects of matching donor with promoter is evident in
Scheme 7(c). When NBS/TESOTf was used as promoter for
coupling the disarmed donor 24 to acceptor 29, the yield of
disaccharide 30 was only 15%. Replacing NBS with NIS
increased the yield to 90%.
In summary, an n-pentenylorthoester (NPOE) and its acid-
catalyzed rearrangement product (NPGAC) can both func-
tion as a glycosyl donor. Although on mechanistic grounds
both should lead to the same product(s), our experiments
have shown that this is frequently not the case. We have
shown that the product(s), whether arising from trans-
orthoesterification, glycosidation, glycosyl esterification,
etc. is dependent on careful choice of the donor, NPOE or
related NPGAC, and also on the reaction conditions,
electrophilic promoter, size of the glycosyl acceptor, and
experimental protocol. The situation is further complicated
by the fact that manno orthoesters are much more robust
than the gluco counterparts. It is therefore recommended
that the latter be stored as a solution in rigorously dry
toluene, and used under the experimental conditions
described for preparation of 30.
Acetylation. This was done using Ac2O, DMAP, pyridine in
dry dichloromethane at room temperature. After completion
(TLC) the reaction mixture was diluted with ethyl acetate
and washed with water, then saturated aqueous sodium
bicarbonate solution and dried. The crude acetate(s) was
(were) purified by column chromatography or by prepara-
tive TLC. Average yield: 80–90%.
Deesterifcation. To a flask containing methanol, sodium
metal was added in small portions (ca. 2 g per 100 ml).
When sodium was fully reacted, the substrate was added as
a solution in dry THF. After completion (TLC, 0.5–1 h) the
reaction mixture was concentrated to dryness, water and
ethyl acetate were added, and the organic layer was washed
with water, brine, dried and concentrated. The final product
was purified by column chromatography.
Efforts are underway to develop conditions in which an
NPOE donor will react, but not its NPGAC rearranged
counterpart. These results will be described in due course.
3.1.1. 3,4,6-Tri-O-benzyl-b-D-mannopyranose 1,2-(pent-
4-enyl orthobenzoate) (17c). a-D-Mannose (20.5 g,
0.114 mol) and DMAP (0.1 g, 0.8 mmol) were dissolved
in pyridine (250 ml) and benzoyl chloride (100 ml,
0.862 mol) was slowly added with cooling and stirring.
The resulting reaction mixture was stirred for 24 h at room
temperature and then evaporated to dryness. The solid
residue was dissolved in CH2Cl2, and water was carefully
added with cooling and vigorous stirring to decompose the
excess of benzoyl chloride. The product (Rf¼0.45 in
Hex/AcOEt 2:1) was extracted with CH2Cl2, processed in
the usual way, and dried to provide the crude pentabenzoate
16a, in approximately 85% yield. The crude material (16a,
85.0 g, 0.121 mol) was dissolved in CH2Cl2 (300 ml) and
acetic anhydride (30.0 ml, 0.318 mol) was added to ensure
anhydrous conditions. The reaction mixture was cooled to
08C, 30% HBr/AcOH solution (250 ml) was slowly added
and the reaction mixture was stirred at 08C for 1 h. The
temperature of the reaction mixture was then raised up to
,108C, the flask was sealed and stored in the refrigerator
(þ58C) overnight. The reaction mixture was then diluted
with cold (2788C) CH2Cl2 and cold water (08C) was added.
The organic layer was washed with cold water, cold
saturated NaHCO3 and dried. After evaporation of solvent
the crude glycosyl bromide 2,3,4,6-tetra-O-benzoyl-a-D-
mannopyranosyl bromide, 16b,21 (Rf¼0.59 in Hex/EtOAc
2:1) was obtained in approximate yield 98% (78.6 g). The
crude glycosyl bromide 16b (73.0 g, 0.111 mol) was
dissolved in dry CH2Cl2 (250 ml), and 2,6-lutidine (20 ml,
0.172 mmol), 4-pentenyl alcohol (14 ml, 0.14 mol), tetra-n-
butylammonium iodide (2.0 g, 5.4 mmol) were added. The
resulting mixture was refluxed under argon for 24 h, when
3. Experimental
All NMR spectra were recorded on GE 300 or Varian
400 MHz NMR spectrometers and chemical shifts are
reported relative to internal TMS. Mass spectrometry was
performed at the Duke University Department of Chemistry
Mass Spectrometry Facility. Chemical Ionization (CI) was
done on a Hewlett–Packard 5988A GC/MS using 1%
ammonia in methane as the reagent gas, with a source
temperature of 1008C, at 1 Torr. High resolution mass
spectra (HRMS) and fast atom bombardment (FAB)
analyses were recorded with a JEOL JMS-SX102A mass
spectrometer operating at 10 K resolution, using a dithio-
threitol/dithioerythritol or m-nitrobenzyl alcohol as the
matrix with xenon as the fast atom. Elemental analyses
were conducted at Atlantic Microlab, Norcross, GA. All
reactions were conducted under argon atmosphere. Thin
layer Chromatography (TLC): Riedel–de Haen, coated with
silicagel 60F 254 and were detected by UV or by spraying or
dipping in a solution of ammonium molybdate (6.25 g) and
cerium (IV) sulfate (25 g) in 10% aqueous sulfuric acid
(250 ml) and subsequent heating. Flash column chromato-
graphy was performed on silica gel (spectrum SIL 58, 230–
400 mesh, grade 60) using mixtures of hexane and ethyl
acetate as eluants. Dichloromethane and toluene were
distilled from CaH2. NBS was crystallized from hot water
and dried on high-vac.

M. Mach et al. / Tetrahedron 58 (2002) 7345–7354
7351
TLC (Rf¼0.59 in Hex/EtOAc 3:1) showed complete
disappearance of 16b. After cooling to room temperature,
water and diethyl ether were added, and the organic layer
was washed with water, brine and dried. After evaporation
the residue was filtered through silica gel using hexane-
s/ethyl acetate (from 9:1 to 4:1) to effect partial purification
from polar impurities. The following spectroscopic data for
17a were completely consistent with the literature values.11
For 17a: Rf¼0.3, Hex/EtOac 4:1, 1H NMR d: 8.10–7.23 (m,
20H, Ph), 5.97 (t, 1H, H-4), 5.81 (d, 1H, H-1), 5.78–5.63
(m, 2H, H-3, CHvCH2), 5.12 (t, 1H, H-2) 4.99–4.85 (m,
2H, CHvCH2), 4.57 (dd, 1H, CH2), 4.39 (dd, 1H, CH2),
4.13 (m, 1H, H-5), 3.42 (t, 2H, CH2), 2.15–2.03 (m, 2H,
CH2), 1.73–1.61 (m, 2H, CH2); 13C NMR d 166.1, 166.0,
165.2 (3Bz), 122.9 (PhC–(OR)3), 114.9 (vCH2), 97.9
(C-1), 30.1, 28.7 (2CH2).
3.68 (dd, 1H, J¼5.4, 11.1 Hz, H-6a), 3.57 (dd, 1H, J¼2.1,
11.1 Hz, H-6b), 3.53–3.47 (m, 1H). 13C NMR (50 MHz,
CDCl3) d: 138.2, 138.1, 137.1, 136.7 (4£OCH2Ph,
quaternary), 129.0–126.7 (arom.), 122.3 ((–O–)2-
C(Ph)OBn), 97.8, 78.3, 76.1 (3£CH), 75.0 (CH and CH2),
74.3 (CH), 73.2, 71.7, 69.1, 66.1 (4£CH2).
(Compound 18c was characterizad by rearrangement to
29—see below).
3.1.3. 3,4,6-Tri-O-benzyl-a-D-glucopyranose 1,2-(pent-4-
enyl orthobenzoate) (20c). a-D-Glucose (20.5 g) was
converted into the glucosyl bromide 19 and thence into
compound 20c using similar steps as described above for the
manno analogue 17c. For 20a: 1H NMR 200 MHz, CDCl3)
d: 8.12–7.20 (m, 20H, arom.), 6.06 (d, 1H, J¼5.2 Hz, H-1),
5.83–5.63 (m, 1H, H-4 from pent.), 5.78 (dd, 1H, J¼1.2,
3.1 Hz), 5.52 (d, broad, 1H, J¼8.8 Hz), 5.01–4.87 (m, 2H),
4.79 (ddd, 1H, J¼1.1, 3.1, 5.1 Hz), 4.53 (dd, 1H, J¼2.9,
12.0 Hz, H-6a), 4.38 (dd, 1H, J¼4.8, 12.0 Hz, H-6b), 4.20–
4.11 (m, 1H), 3.43–3.25 (m, 2H), 2.15–2.01 (m, 2H), 1.68–
1.54 (m, 2H). 13C NMR 50 MHz, CDCl3) d: 165.8, 165.0,
164.4 (3£C(O)Ph), 137.7 (C-4 from pent.), 133.5–126.1
(arom.), 121.1 (quaternary from orthoester), 114.8 (CH2
from pent.), 97.4, 72.0, 69.1, 68.4, 67.4 (5£CH), 63.9, 63.4.
30.1, 28.6 (4£CH2). For 20b: 1H NMR (200 MHz, CDCl3)
d: 7.68–7.28 (m, 5H, arom.), 5.86 (d, 1H, J¼5.1 Hz, H-1),
5.83–5.64 (m, 1H, H-4 from pent.), 5.01–4.98 (m, 2H),
4.41–4.26 (m, 2H), 3.81 (dd, 1H, J¼4.8, 5.0 Hz), 3.66 (s,
broad, 2H), 3.50–3.45 (m, 1H), 3.35–3.28 (m, 2H), 2.10–
2.00 (m, 2H), 1.67–1.53 (m, 2H). 13C NMR (50 MHz,
CDCl3) d: 137.7 (C-4 from pent.), 136.5 (arom. quaternary),
129.1, 128.2, 125.0 (3£CH arom.), 119.7 (quaternary from
orthoester), 114.7 (CH2 from pent.), 97.9, 76.7, 73.0, 72.6,
68.1 (5£CH), 63.0, 61.2. 30.1, 28.6 (4£CH2). The title
compound 20c was prepared from 20b as described above
(for 17c) in 84% yield. For 20c: 1H NMR 300 MHz, CDCl3)
d: 7.66–7.14 (m, 20H, arom.), 5.95 (d, 1H, J¼5.1 Hz, H-1),
5.83–5.70 (m, 1H, H-4 from pent.), 5.02–4.93 (m, 2H),
4.74–4.33 (m, 7H), 3.90 (t, 1H, J¼3.7 Hz), 3.78–3.68 (m,
2H), 3.60 (d, broad, 2H, J¼2.9 Hz), 3.35–3.27 (m, 2H),
2.11–2.04 (m, 2H), 1.67–1.57 (m, 2H). 13C NMR 50 MHz,
CDCl3) d: 137.9 (quaternary benzyl), 137.8 (C-4 from
pent.), 137.5, 136.1 (2£quaternary benzyl), 128.8–126.1
(arom.), 120.0 (quaternary from orthoester), 114.7 (CH2
from pent.), 98.0, 77.8, 75.3, 74.9 (4£CH), 73.0, 72.5, 71.9
(3£CH2OPh), 70.2 (CH), 68.9, 63.0, 30.2, 28.7 (4£CH2).
The benzoyl groups of compound 17a were removed under
the general deesterifation conditions. Column chromato-
graphy {(Hex/EtOAc (4:1)!ethyl acetate!EtOAc/Hex
(9:1)} afforded the triol 17b as a colorless syrup, 29.0 g,
(68% total yield from a-D-mannose). The resulting triol 17b
(14.0 g, 37.4 mmol) and imidazole (0.25 g, 3.67 mmol)
were dissolved in dry DMF (100 ml). Sodium hydride
(11.0 g of 60% dispersion in mineral oil, 0.764 mol) was
slowly added and the reaction mixture was stirred at room
temperature for 20 min. Benzyl bromide (20 ml,
0.17 mmol) was added in portions, in such a way that the
temperature of the reaction mixture (both during generation
of anion and addition of benzyl bromide) did not exceed
708C. The reaction mixture was stirred for 2 h and then
diethyl ether was added. Excess of sodium hydride was
decomposed by careful addition of water, and the organic
layer was washed with water, brine and dried. After
evaporation and purification by column chromatography
(Hex/EtOAc 9:1!3:1) product 17c was obtained as an oil
(23 g, 95%). The following data for 17c was in complete
agreement with the literature data.11 For 17c: Rf¼0.49, Hex/
1
EtOAc 4:1, H NMR d: 7.78–7.21 (m 20H, Ph), 5.87 (m,
1H, CHvCH2), 5.52 (d, 1H, H-1), 5.13–4.85 (m, H), 4.51–
4.41 (m, H), 4.09–3.41 (m, H), 2.27–2.18 (m, 2H, CH2),
1.82–1.70 (m, 2H, CH2); 13C NMR d 122.2 (PhC(OR)3)
114.9 (vCH2), 97.8 (C-1), 30.3, 28.8 (2CH2).
3.1.2. 3,4,6-Tri-O-benzyl-b-D-mannopyranose 1,2-(ben-
zyl orthobenzoate) (18c). The mannosyl bromide 16b was
converted into compound 18a as described above for the
NPOE 17a, replacing 4-pentenol with benzyl alcohol to give
1
the benzyl analogue 18a: H NMR (200 MHz, CDCl3) d:
(HR, LSIMS) Calcd for C39H42O7Na: 645.2828; found:
645.2843 (MþNaþ).
8.10–7.18 (m, 25H, arom.), 5.96 (t, 1H, J¼9.5 Hz), 5.78 (d,
1H, J¼2.9 Hz), 5.68 (dd, 1H, J¼3.9, 10.1 Hz), 5.40 (dd, 1H,
J¼3.1, 3.6 Hz), 4.58 (dd, 1H, J¼3.3, 12.0 Hz, H-6a), 4.45
(s, 2H), 4.38 (dd, 1H, J¼4.7, 12.0 Hz, H-6b), 4.15–4.06 (m,
1H). 13C NMR (50 MHz, CDCl3) d: 165.8, 165.6, 164.9
(3£C(O)Ph), 137.3–120.4 (arom.), 122.8 ((–O–)2-
C(Ph)OBn), 97.8, 76.1, 72.0, 70.8 (4£CH), 66.4 (CH and
C H2Ph), 63.0 (CH2). Debenzoylation and benzylation, as
used above, then led to the compound 18c in 85% yield. For
3.1.4. Acid catalyzed rearrangement of gluco n-pent-
enylorthoester (NPOE) 20c. (i) With added n-pentenyl
alcohol. The NPOE 20c (0.5 g, 0.803 mmol) and 4-pentenol
(20 ml, 0.044 mmol) were dissolved under argon in dry
CH2Cl2 (10 ml) and TBDMSOTf (10 ml, 0.044 mmol) was
added. The reaction mixture was stirred at room temperature
for 2 min and then diluted with diethyl ether. Water was
added and the organic layer was washed with saturated
NaHCO3, water, brine then dried and concentrated. Column
chromatography (hexanes/ethyl acetate from 9:1 to 3:1)
provided 0.470 g of 4-pentenyl 2-O-benzoyl-3,4,6-tri-O-
benzyl-b-D-glucopyranoside (24) in 97% yield. For 24:
1
18c H NMR (300 MHz, CDCl3) d: 7.76–7.23 (m, 25H,
arom.), 5.49 (d, 1H, J¼3.9 Hz, H-1), 4.90 (d, 1H,
J¼11.1 Hz), 4.75–4.62 (m, 4H), 4.50 (AB signal, 2H,
J¼11.7, 15.3 Hz), 4.42 (AB signal 2H, J¼12.3, 15.9 Hz),
3.98 (dd, 1H, J¼8.7, 9.6 Hz), 3.82 (dd, 1H, J¼3.6, 8.7 Hz),

7352
M. Mach et al. / Tetrahedron 58 (2002) 7345–7354
([a]D¼25.98 c¼1.4, CHCl3) 1H NMR (500 MHz, CDCl3) d:
8.02–8.00 (m, 2H, ortho protons from benzoate), 7.57–7.12
(m, 18H, arom.), 5.68–5.60 (m, 1H, H-4 from pent.), 5.26
(dd, 1H, J¼8.0, 9.3 Hz, H-2), 4.83–4.56 (m, 8H), 4.50 (d,
1H, J¼7.9 Hz, H-1), 3.90–3.71 (m, 5H), 3.55 (ddd, 1H,
J¼2.0, 4.8, 9.7 Hz), 3.48–3.44 (m, 1H), 2.01–1.89 (m, 2H),
1.66–1.56 (m, 2H). 13C NMR (50 MHz, CDCl3) d: 165.0
(CvO), 138.0 (quaternary benzyl), 137.8 (double intensity:
C-4 from pent. and quaternary benzyl), 137.6 (quaternary
benzyl), 132.9–127.5 (arom.), 114.6 (CH2 from pent.),
101.0, 82.7, 78.0, 75.2 (4£CH), 74.9 (double intensity:
2£CH2OPh), 73.8 (CH), 73.4 (OCH2Ph), 68.8, 68.7, 29.8,
28.6 (4£CH2).
treated as in part a (i), the reaction gave the anomeric
mixture 25a (a and b) exclusively in 98% yield. The
anomers were partially separated by preparative TLC and
acetylated. For 1-O-acetyl-2-O-benzoyl-3,4,6-tri-O-benzyl-
a-D-mannopyranose (23ba): 1H NMR d: 8.06 (d, 2H,
J¼7.2 Hz, ortho protons from benzoate), 7.58–7.18 (m,
18H, arom), 6.24 (d, 1H, J¼2.1 Hz, H-1), 5.61 (t, 1H,
J¼3.0 Hz, H-2), 4.89–4.72 (m, 3H), 4.61–4.52 (m, 3H),
4.18 (dd, 1H, J¼8.7, 9.6 Hz), 4.09 (dd, 1H, J¼2.7, 9.3 Hz),
3.93–3.89 (m, 2H), 3.79–3.74 (m, 1H), 2.10 (s, 3H,
C(O)CH3). For 1-O-acetyl-2-O-acetyl-2-O-benzoyl-3,4,6-
1
tri-O-benzyl-b-D-mannopyranose (23bb) H NMR d: 8.11
(d, 2H, J¼7.2 Hz, arom. ortho protons from benzoate),
7.60–7.16 (m, 18H, arom), 5.84–5.83 (m, 2H, H-1 and
H-2), 4.89–4.72 (m, 3H), 4.58–4.53 (m, 3H), 4.10 (t, 1H,
J¼9.6 Hz), 3.91–3.80 (m, 3H), 3.68–3.63 (m, 1H), 2.05 (s,
3H, C(O)CH3).
(ii) Without added n-pentenyl alcohol. When the reaction in
part (i) was done without addition of pent-4-enol, a rapid
rearrangement (,2 min) gave compound 24 along with
1-O-benzoyl-3,4,6-tri-O-benzyl-a-D-glucopyranose (22a)
1
as a 4.8:1 mixture. For 22a: H NMR (300 MHz, CDCl3)
For 23ba: low resolution mass (FAB) C35H36O6 calcd
552.67; Found 551.6 (Mþ21).
d: 8.02 (d, 2H, J¼7.2 Hz, ortho protons from benzoate),
7.61–7.15 (m, 18H, arom.), 6.48 (d, 1H, J¼3.0 Hz, H-1),
5.00–4.82 (m, 3H), 4.67–4.48 (m, 3H), 3.98–3.78 (m, 5H),
3.68 (dd, 1H, J¼2.1, 10.8 Hz), 2.11 (s, broad, 1H, –OH).
Acetylated under the standard conditions gave 22b: 1H
NMR (300 MHz, CDCl3) d: 8.05 (d, 2H, J¼7.3 Hz, ortho
protons from benzoate), 7.52–7.13 (m, 18H, arom.), 6.56
(d, 1H, J¼3.6 Hz, H-1), 5.16 (dd, 1H, J¼3.6, 10.3 Hz, H-2),
4.90–4.77 (m, 3H), 4.67–4.51 (m, 3H), 4.12 (dd, 1H,
J¼8.8, 10.3 Hz), 4.04 (d, broad, J¼10.3 Hz), 3.92 (t, 1H,
J¼9.5 Hz), 3.82 (dd, 1H, J¼3.7, 11.0 Hz, H-6a), 3.70 (dd,
1H, J¼1.5, 11.0 Hz, H-6b), 1.94 (s, 3H, C(O)CH3).
(ii) Hydrolysis of the manno NPGAC 21a provided a mixture
of 25a (a and b) see above part b (i), and a trace of
bromohydrin 26.14
3.1.7. 3,4,6-Tri-O-benzyl-a-D-glucopyranose 1,2-(iso-
propyl orthobenzoate) (27). 3,4,6-Tri-O-benzyl-a-D-
glucopyranose 1,2-(pent-4-enyl orthobenzoate), 20c
(0.250 g, 0.401 mmol) and freshly distilled isopropanol
(middle fraction, 0.4 ml, 5.2 mmol) were dissolved in dry
dichloromethane (6 ml) under argon. Iodonium dicollidine
triflate (IDCT)24 (0.420 g, 0.810 mmol) was added and the
reaction mixture was stirred for 30 min at room temperature,
at which time TLC (Hex/EtOAc 4:1) showed disappearance
of the starting material and formation of a new product. To
the reaction mixture was then added 10% aqueous Na2S2O3
and ethyl acetate. The organic layer was washed with water,
brine, dried over sodium sulfate and concentrated. Column
chromatography of the residue with (Hex/EtOAc 9:1!4:1)
provided an exo/endo mixture of the epimeric transortho-
Low. resolution mass (FAB) C35H36O Calcd 552.67; Found
551.7 (Mþ21).
3.1.5. Pentenyl 2-O-benzoyl-3,4,6-tri-O-benzyl-a-D-man-
nopyranoside (21a). 3,4,6-Tri-O-benzyl-b-D-mannopyra-
nose 1,2-(pentenyl orthobenzoate) 17c (23 g, 36.933 mmol)
was azeotroped on rotavap with toluene, then dried under
high-vacuum. Rearrangement in the presence of pent-4-
enol, conducted as described above for 20c!24, required
,5 min to provide 19.4 g of product 21a (84% yield). The
physical constant agreed completely with the material
previously prepared by a more lengthy route.11
1
esterification products 27 in 78% yield. For 27: H NMR
(300 MHz, CDCl3, selected signals) d: 5.95–5.93 (m, both
H-1 protons in ca. 1:4 ratio and J¼ca. 5.0 Hz), 1.18–1.04
(m, 6H, C(CH3)2). 13C NMR (75 MHz, CDCl3, selected
signals) d: 120.4, 120.1 (both quaternary carbons), 98.0,
97.9 (both C-1), 23.3, 22.1 (both C(C H3)2).
3.1.6. Oxidative hydrolysis of n-pentenylorthoesters
(NPOEs) and NPGsAC. (a) Gluco donors. (i) The gluco
NPGAC (24) upon being subjected to the general conditions
for oxidative hydrolysis gave only a mixture of the anomeric
glucoses, 23a in 92% yield (a/b¼4:1). The material was
identified by acetylation. Selected signals for the resulting
anomeric acetates: For 23ba: 1H NMR (300 MHz, CDCl3)
d: 6.44 (d, 1H, J¼3.6 Hz, H-1), 5.32 (dd, 1H, J¼3.6,
10.2 Hz, H-2), 2.09 (s, 3H, C(O)CH3). For 23bb d: 5.79 (d,
1H, J¼8.1 Hz, H-1), 5.40 (dd, 1H, J¼8.1, 8.7 Hz, H-2), 2.00
(s, 3H, C(O)CH3).
Low resolution mass (FAB) C37H40O7 Calcd 596.71; Found
595.7 (Mþ21), 597.1 (Mþþ1).
3.1.8. Benzyl 3,4,6-tri-O-benzyl-a-D-mannopyranose
1,2-(isopropyl orthobenzoate) (28). 3,4,6-Tri-O-benzyl-
b-D-mannopyranose 1,2-(pent-4-enyl orthobenzoate), 17c,
was treated as described above for 20c, leading to 28 in 76%
1
as the only product. For 28: H NMR (300 MHz, CDCl3,
selected signals) d: 5.49–5.47 (m, both H-1 protons in ca
1:4 ratio and J¼ca. 3.0 Hz), 1.52–1.09 (m, 6H, C(CH3)2).
13C NMR (75 MHz, CDCl3, selected signals) d: 122.5,
122.1 (both quaternary carbons), 97.7, 97.5 (both C-1), 23.6,
23.3 (both C(CH3)2).
(ii) When the gluco NPOE (20c), was subjected to similar
hydrolysis, the above described glucopyranose (23a) and
benzoyl-3,4,6-tri-O-benzyl-a-D-glucopyranose (22a) were
obtained as a 10:1 mixture in 96% yield.
Low resolution mass (FAB) C37H40O7 Calcd 596.71; found
595.7 (Mþ21), 598.7 (Mþþ2).
(b) Manno donors. (i) When the manno NPOE (17c), was

M. Mach et al. / Tetrahedron 58 (2002) 7345–7354
7353
3.1.9. Benzyl 3,4,6-tri-O-benzyl-a-D-mannopyranoside
(29). The benzyl orthobenzoate 18c was rearranged to
benzyl mannoside 21b as described above for 17c!21a.
The benzoyl group of compound 21b (19.2 g, 29.779 mmol)
was removed under the general deesterification conditions.
Product 29 (Rf¼0.4, Hex/EtOAc 3:2) was obtained as a
colorless syrup, 14.8 g (92% yield) after column chroma-
tography (Hex/EtOAc 4:1!1:1). For 29: ([a ]D¼57.88
c¼1.36, CHCl3).
Literature:25 48.08 (c¼1.85, CHCl3),26 48.08 (c¼0.6,
CHCl3).27 1H NMR (200 MHz, CDCl3) d: 7.38–7.15 (m,
20H, arom.), 4.99 (d, 1H, J¼1.6 Hz, H-1), 4.84–4.45 (m,
8H), 4.06 (s, broad, 1H), 3.91–3.66 (m, 5H), 2.61 (d, 1H,
J¼2.6 Hz, OH). 13C NMR 50 MHz, CDCl3) d: 138.09,
138.05, 137.8, 137.0 (4£OCH2Ph, quaternary), 128.5.0–
127.3 (arom.), 98.4, 80.2 (2£CH), 75.1 (CH2), 74.2 (CH),
73.4, 71.9 (2£CH2), 71.2 (CH), 69.0, 68.8 (2£CH2), 68.3
(CH).
4.48 (m, 11H), 4.38–4.15 (m, 5H), 3.89 (dd, 1H, J¼3.0,
8.1 Hz), 3.82–3.53 (m, 9H), 3.26 (dd, 1H, J¼6.6, 10.8 Hz).
13C NMR (50 MHz, CDCl3) d: 164.8 (CvO), 138.5, 138.4,
138.3, 137.8, 137.7 (double intensity), 137.1 (7£OCH2Ph,
quaternary), 132.8–127.5 (arom.), 99.9, 96.4, 82.6, 77.9,
77.8, 75.3 (6£CH), 75.0 (CH2), 74.9 (CH), 74.80, 74.75
(2£CH2), 74.1, 73.6 (2£CH), 73.5, 73.0 (2£CH2), 72.2
(CH), 70.9, 70.0, 69.2, 68.7 (4£CH2).
Low resolution mass (FAB) C68H68O12 Calcd 1077.29;
Found 1076.12 (Mþ21), 1079.01 (Mþþ2).
3.1.11. 3,4,6-Tri-O-benzyl-a-D-glucopyranose 1,2-(ben-
zyl 3,4,6-tri-O-benzyl)-a-D-mannopyranosyl ortho-
benzoate) (31). (The experiment was carried out as in the
preceding case, except that the promoter was now IDCT).24
The mannopyranoside acceptor 29 (0.250 g, 0.462 mmol)
which had been previously azeotroped with toluene and
dried on high-vaccuum was dissolved in dry dichloro-
methane (25 ml) under argon. Molecular sieves were added
followed by the NPOE 20c (0.750 g, 1.204 mmol), as a
solution in dry toluene. Iodonium dicollidine triflate
(IDCT)24 (1.0 g, 1.929 mmol) was added and the reaction
mixture was stirred for 30 min at room temperature, at
which time the reaction mixture was quenched with 10%
aqueous Na2S2O3, and extracted with ethyl acetate. The
organic layer was washed with water, brine, dried over
sodium sulphate and concentrated. Column chromatography
(Hex/EtOAc 9:1!4:1) provided the title compound 31 in
65% yield. It was found that product 31 did not respond to
treatment with sodium methoxide.
(HR, LSIMS) Calcd for C34H36O6Na: 563.2410; found:
563.2410 (MþNaþ).
3.1.10. Benzyl 3,4,6-tri-O-benzyl-O-(2-O-benzoyl-3,4,6-
tri-O-benzyl-b-D-glucopyranosyl)-(1!2)-a-D-manno-
pyranoside (30). (i) The acceptor, 29 (2.36 g, 4.37 mmol)
and an excess of 3,4,6-Tri-O-benzyl-a-D-glucopyranose
1,2-(pent-4-enyl orthobenzoate) 20c (8.16 g, 13.10 mmol)
were azeotroped separately with toluene and dried in vacuo.
Acceptor 29 was dissolved in dry dichloromethane
(120 ml), and molecular sieves and NBS (3.11 g,
17.47 mmol) were added. The reaction mixture was stirred
under argon for 5 min to dissolve NBS, and then TESOTf
(0.300 ml, 1.327 mmol) was added. The reaction mixture
was stirred for further 5 min, and then donor 20c, dissolved
in dry toluene (20 ml), was added dropwise over ,10 min
via a syringe at room temperature. Stirring was continued
for an additional 20 min at which time the reaction was
quenched with 10% Na2S2O3 and saturated NaHCO3
aqueous solutions. The molecular sieves were filtered and
washed with Et2O, and the organic layer was washed with
water, brine and dried. Column chromatography (Hex/
EtOAc 9:1!3:1) provided the title compound 30 in 73%
(3.43 g).
1H NMR (300 MHz, CDCl3) d: 7.65–7.11 (m, 40H, arom.),
5.92 (d, 1H, J¼5.7 Hz, H-1gluco), 4.88 (d, 1H, J¼10.5 Hz),
4.74–4.38 (m, 15H), 4.31 (dd, 1H, J¼5.7, 11.7 Hz,
H-2gluco), 3.92–3.71 (m, 6H), 3.66 (s, 2H), 3.56 (s, 2H).
13C NMR (75 MHz, CDCl3) d: 138.3 (double intensity),
138.1, 137.9, 137.6, 137.2, 135.8 (7£OCH2Ph, quaternary),
129.2–126.5 (arom), 120.3, (quaternary), 98.0, 97.3 (both
C-1), 78.7, 77.6, 75.1 (double intensity), 74.7, 74.6, 73.2,
73.0, 72.5, 71.9, 71.7, 71.6, 70.0 (double intensity), 69.3,
68.9, 68.7 (17 signals from benzyl groups and carbohydrate
carbon atoms). The 13C NMR data showed that compound
32 was obtained as a single diastereoisomer.
(ii) Pent-4-enyl 3,4,6-tri-O-benzyl-2-O-benzoyl-b-D-gluco-
pyranoside, 24 (2.21 g, 3.54 mmol) and acceptor 29 (0.96 g,
1.77 mmol) were azeotroped together with toluene. The
resulting dry syrup was redissolved in dry CH2Cl2 (25 ml) at
08C. Molecular seives and NIS (1.2 g, 5.51 mmol) were
stirred for 3 min and then TBDMSOTf (0.117, 0.44 mmol)
was added. The reaction mixture was kept at room
temperature for 30 min, and then the reaction was quenched
with 10% Na2S2O3 and saturated NaHCO3 aqueous
solutions. The molecular sieves were filtered and washed
with Et2O and the organic layer was washed with water,
brine and dried. Column chromatography (Hex/EtOAc 4:1)
provided compound 30 in 89% along with 6% of the
corresponding a-anomer.
3.1.12. Attempted conversion of orthoester 31 into
disaccharide 30. Compound 31 (200 mg) was dissolved
in dry dichloromethane, a catalytic amount of camphor-
sulfonic acid (CSA) was added and the reaction mixture was
stirred at room temperature for 30 min. At this time the
starting material (Rf¼0.42 Hex/EtOAc 4:1) had disappeared
completely, and two polar products (Rf¼0.19 (29) and 0.27
(22a) Hex/EtOAc 4:1) were formed quantitatively.
3.1.13. Benzyl 3,4,6-tri-O-benzyl-O-(2-O-beznoyl-3,4,6-
tri-O-benzyl-b-D-glucopyranosyl)-(1!2)-O-(3,4,6-tri-O-
benzyl-b-D-mannopyranosyl)-(1!2)-a-D-mannopyra-
noside (33). The disaccharide29 benzyl 3,4,6-tri-O-benzyl-
O-(3,4,6-tri-O-benzyl-b-D-mannopyranosyl)-(1!2)-a-D-
mannopyranoside, 32, (4.0 g, 4.11 mmol) and 20c (8.5 g,
13.65 mmol) were azeotroped together with toluene, dried
in vacuo and dissolved under argon in dry dichloromethane
(60 ml). Molecular sieves were added and after the reaction
For 30: 1H NMR (300 MHz, CDCl3) d: 7.94 (d, 2H,
J¼7.2 Hz, ortho protons from benzoate), 7.39–7.13 (m,
38H, arom.), 5.38 (dd, 1H, J¼8.1, 8.7 Hz, H-2gluco), 4.83–

7354
M. Mach et al. / Tetrahedron 58 (2002) 7345–7354
286–292. Ogawa, T.; Nukada, T. Carbohydr. Res. 1988, 136,
135–152.
mixture had beeen stirred at room temperature for 15 min,
IDCT (8.5 g, 16.40 mmol) was added. The stirring was
prolonged for another 30 min before the reaction was
quenched with 10% Na2S2O3. Molecular sieves were
filtered off and washed with diethyl ether, and the filtrate
extracted with diethyl ether. The organic layer was washed
with 2% aqueous H2SO4 to remove any collidine and to
decompose transorthoesterification products, and then with
water, saturated NaHCO3, brine, before being dried and
concentrated. The resulting dark syrup was filtered through
a thin layer of silica gel. The filtrate was concentrated and
subjected to column chromatography (Hex/EtOAc
9:1!3:2), which provided trisaccharide 34 (2.86 g) in
67% yield based on recovered acceptor 32(1.26 g). NMR
11. Roberts, C.; Madsen, R.; Fraser-Reid, B. J. Am. Chem. Soc.
1995, 117, 1546.
12. For convenient summaries see: (a) Veeneman, G. H. In
Carbohydrate Chemistry. Blackie, G.-J., Ed.; Academic and
Professional: London, 1998. (b) Bochkov, A. F.; Zaikov, G. E.
Chemistry of the O-Glycosidic Bond. Pergamon: Oxford,
1979; Chapter 2.
13. Betaneli, V. I.; Ovchinikov, M. V.; Backinowsky, L. V.;
Kochetkov, N. K. Carbohydr. Res. 1982, 107, 285–291.
14. Fraser-Reid, B.; Udodong, U. E.; Wu, Z.; Ottosson, H.;
Merritt, J. R.; Rao, C. S.; Roberts, C.; Madsen, R. Synlett 1992,
927.
1
data for 34: H NMR (300 MHz, CDCl3) d: 8.0 (d, 2H,
15. (a) Ramu, K.; Baker, J. K. J. Med. Chem. 1995, 38,
1911–1921. (b) Kanaoka, M.; Kato, H.; Yano, S. Chem.
Pharm. Bull. 1990, 38, 221–224. (c) Mattox, B. R.; Goodrich,
J. E.; Nelson, A. N. Steriods 1982, 40, 23. (d) Marra, A.; Bond,
X.; Fetitou, M.; Sinay, P. Carbohydr. Res. 1989, 195, 39–50.
(e) Hashimoto, S.; Sano, A.; Umeo, K.; Nakajima, M.;
Ikegani, S. Chem. Pharm. Bull. 1995, 43, 2267–2269.
16. Schmidt, R. R.; Grundler, G. Synthesis 1981, 885–887. Marra,
A.; Dong, X.; Petitou, M.; Sinay, P. Carbohyd. Res. 1989, 195,
39–50. Vaccaro, W. D.; Davis, Jr. H. R. Bioorg. Med. Chem.
Lett. 1998, 8, 313–318. Berrang, B.; Brine, G. A.; Carroll, I. F.
Synthesis 1991, 10, 1165–1168.
J¼7.2 Hz, ortho protons from benzoate), 7.39–7.06 (m,
53H, arom.), 5.59 (d, 1H, J¼7.8 Hz, H-1gluco), 5.38 (dd, 1H,
J¼7.8, 8.1 Hz, H-2gluco), 4.98–4.16 (m, 22H), 4.04–3.44
(m, 15H), 3.34 (t, 1H, J¼8.1 Hz), 2.94 (dd, 1H, J¼7.5,
10.5 Hz).
(HR, LSIMS) Calcd for C95H96O17: 1509.81; found: 1511.
1
56 (Mþ ).
Acknowledgments
17. (a) King, J. F.; Allbutt, A. D. Tetrahedron Lett. 1967, 49–54.
(b) King, J. F.; Allbutt, A. D. Can. J. Chem. 1970, 48,
1754–1769.
B. F. R. is grateful to the Human Frontier Science Program
Organization and Synthon Chiragenics of Monmouth
Junction, NJ, USA for partial support of this work. K. C.
H. is thankful to PHS R)1 AI43997 for support.
18. Deslongchamps, P. Stereoelectronic Effects in Organic
Chemistry. Pergamon: New York, 1983; Chapter 3.
19. Micheel, F.; Micheel, H. Chem. Ber. 1930, 63, 386–387.
20. Isbell, H. S.; Frush, H. L. J. Res. Natl Bur. Stand. 1949, 43,
161–171.
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