A chemoenzymatic synthesis of differentially protected D-Talose derivatives

Article abstract of DOI:10.1071/CH02041

The synthesis of the D-talose derivatives from the readily available and enantiomerically pure cis-1,2-dihydrocatechol was discussed. The synthesis included a stannylene acetal-mediated epimerization process. The dehydroxylation of D-galactal provided a different route to target. The triacetates were chemically correlated with known derivatives of D-talose. A mixture of these compounds was also subjected to reaction with aqueous trifluoroacetic acid to affect global deprotection and generate D-talose.

Full text of DOI:10.1071/CH02041

P u b l i s h i n g
AUSTRALIAN JOURNAL OF
CHEMISTRY
A N I N T E R N A T I O N A L J O U R N A L F O R C H E M I C A L S C I E N C E
publishing research papers from all fields of chemical
science, including synthesis, structure, new materials,
macromolecules, supramolecular chemistry, biological
chemistry, nanotechnology, surface chemistry, and
analytical techniques.
Volume 55, 2002
© CSIRO 2002
All enquiries and manuscripts should be directed to:
Dr Alison Green
Australian Journal of Chemistry–
an International Journal for Chemical Science
CSIRO
PUBLISHING
PO Box 1139 (150 Oxford St)
Collingwood, Vic. 3066, Australia
Telephone: +61 3 9662 7630
Fax: +61 3 9662 7611
E-mail: publishing.ajc@csiro.au
CSIRO
Published by
PUBLISHING
for CSIRO and the Australian Academy of Science
w w w. p u b l i s h . c s i r o . a u / j o u r n a l s / a j c

Aust. J. Chem. 2002, 55, 95–103
A Chemoenzymatic Synthesis of
Differentially Protected D-Talose Derivatives
Martin G. Banwell,A,B Alison J. Edwards,A John N. Lambert,C
Xing Hua MaA and Keith G. WatsonC
A Research School of Chemistry, Institute of Advanced Studies, The Australian National University,
Canberra, ACT 0200, Australia.
B Author to whom correspondence should be addressed (e-mail: mgb@rsc.anu.edu.au).
C Biota Chemistry Laboratory, Chemistry Department, Monash University, Clayton, Vic. 3168, Australia.
The synthesis of the D-talose derivatives (10)–(14) from the readily available and enantiomerically pure cis-1,2-
dihydrocatechol (2) is described. The structures of compounds (7) and (13) have been established by single-crystal
X-ray analyses.
Manuscript received: 25 February 2002.
Final version: 30 March 2002.
C
H
02041
A
C
h e
m
o
e
n
z
m
a
i
S
ynht
e
s
i
o
f
D
i
f
er
e
nita
l
lyP
r
ote
c
te
d
D
-
T
a
ol
s
e
D
e
r
v
t
ive
s
M
.
G
.
B
a
n
w
l
l,
A
.
J
.
d
w
a
r
d
,
J
.
N
.
a
m
b
e
r
,t
X
.
H
.
M
aandK
.
G
.
W
a
t
s
n
Introduction
of useful implications in molecular recognition processes[10]
and may be responsible for the capacity of this sugar to
reduce molybdenum inhibition of the growth of the yeast
Saccharomyces cerevisiae.[11]
D-Talose [D-talo-hexose, (1)], one of the rarer D-
aldohexoses, as well as certain deoxy-derivatives, represent
key residues associated with a range of biologically
significant entities. The first reported occurrence of this
hexose was by Hesse who, in 1902, described the isolation of
a hydrate as a hydrolysis product of cocacitrin.[1] More
recently, D-talose has been identified[2] as the central motif
Given the foregoing it is not surprising that some effort
has been directed to the preparation of the title compound
and various derivatives. The most common and perhaps
obvious route to D-talose has been by C2 epimerization of the
more abundant D-galactose, a conversion that can be
achieved directly through the agency of various molybdenum
species,[12] or by multi-step sequences.[13] A practical and
recently reported synthesis of D-talose involves a stannylene
acetal-mediated epimerization process.[14] The dihydroxy-
lation of D-galactal provides another route to target (1).[15]
Paulsen has also reported[16] a simple synthesis of D-talose
by acetoxonium rearrangement of D-galactose. In related
work, 1,6-anhydro-β-D-talopyranose has been prepared from
the C2 epimeric 1,6-anhydro-β-D-galactopyranose by an
oxidation/reduction sequence.[17]
A concise syntheses of D-talose has recently been
developed by O’Doherty[18] and involves the asymmetric
dihydroxylation of furfural.* The synthesis of differentially
protected talose derivatives has also been the subject of some
effort with the work just described providing access to such
species on route to the final target, i.e. (1). Not surprisingly,
the selective manipulation of D-talose itself has also provided
methods for accessing useful derivatives,[21] while regimes
involving manipulations (including inversion at C2) of a
associated with the aminoglycoside hygromycin
B
(produced by S. hygroscopicus) which acts as a broad
spectrum antibiotic and is used in veterinary medicine as an
anthelmintic, especially against acarids.[3] 6-Deoxy-D-talose
(D-talomethylose) is obtained by hydrolysis of the capsular
polysaccharide of Gram-negative bacteria.[4] It has also been
identified in an extracellular polysaccharide produced by the
ruminal bacterium Butyrivibrio fibrisolvens X6C61[5] and in
the serotype c polysaccharide antigen from Actinbacillus
actinomycetemcomitans.[6] An O-acetylated homopoly-
saccharide of 6-deoxy-D-talose (6-deoxy-α-D-talan poly-
mer) has recently been isolated from Burkholderia (Pseudo-
monas) plantarii DSM 65357 while 3-O-methyl-6-deoxy-D-
talose has been identified in lipopolysaccharides of
Rhodopseudomonas palustris.[8] D-Talose has found use as a
bulking and/or browning agent in food preparation.[9]
Further, since it also has the same natural taste as sucrose,
D-talose can be used as a low-calorie sweetening agent.[9]
The ‘all-cis’ arrangement of the non-anomeric hydroxy
groups in the pyranose form of compound (1) has a number
*
The concise synthesis of L-talose from non-carbohydrate sources was achieved using asymmetric epoxidation methodology (see reference 19 and
references therein). More recent syntheses have been reported by Vogel, Marshall, and Ogasawara (see reference 20).
© CSIRO 2002
10.1071/CH02041
0004-9425/02/010095

96
M. G. Banwell et al.
galactose derivative have also been reported.[22] Chain-
extension approaches employing the Henry reaction of D-
lyxose and its derivatives have provided efficient syntheses
of various amino-deoxy-D-talose derivatives.[23]
from (2)]. Since, like precursor (4), compound (5) was
particularly prone to elimination processes (leading to
aromatic products) it was immediately subject to the next
step of the reaction sequence, namely selective epoxidation
of the non-chlorinated double-bond using m-
chloroperbenzoic acid (m-CPBA). In this manner, the
diastereoisomeric and chromatographically separable
epoxides (6) (58%) and (7) (18%) were obtained, with the
predominance of the former product being determined by the
steric demands of the TBDPS and (to a lesser extent) acetyl
moieties that direct epoxidation to the less congested β-face
of the non-chlorinated double-bond with compound (5). The
appearance of three additional signals [relative to the 18 seen
in isomer (6)] in the low-field region of the 13C NMR
spectrum of the minor isomer (7) is attributed to the
restricted rotation of the aromatic rings associated with the
TBDPS group in this highly congested ‘all-cis’ substituted
cyclohexene. Confirmation of the structure of products (6)
and (7) follows from a single-crystal X-ray analysis of the
latter (see Fig. 1, Tables 1, 2 and Experimental Section).
In keeping with earlier observations,[28] reaction of
epoxide (7) with aqueous acid results in the opening of the
three-membered ring by a pathway involving nucleophilic
attack at the allylic carbon, so as to form the required
conduritol derivative (9). However, the choice of acid
catalyst for this conversion was critical. Thus, when HCl in
aqueous tetrahydrofuran (THF) was employed only minor
amounts (12%) of the required compound, (9), were
obtained, with the corresponding chlorohydrin (see
Experimental) being the predominant product (55%). In
contrast, when phosphoric acid was employed as catalyst
then target (9) predominated (71%), although significant
amounts (20%) of a product, (8), incorporating the elements
of THF, were obtained. Compound (9) embodies the
necessary stereochemical array of hydroxy residues for
elaboration to D-talose derivatives. To this end, the alkenyl
halide residue within substrate (9) was subjected to reaction
with ozone at –78°C and the intermediate hydroperoxy
species[25e] reduced by workup with sodium borohydride. In
this way the D-talonic acid γ-lactone (10) was obtained, albeit
in a modest yield of 54%. Compound (10) was readily
converted by standard methods into the corresponding and
more easily handled acetonide (11) (82%), which was
subject to full analytical and spectroscopic characterization.
The elaboration of compound (11) to protected forms of
D-talose was straightforward and involved reduction of the
lactone carbonyl. This could be achieved using
diisoamylborane[29] and in this manner lactol (12) (83%) was
obtained as a ca. 2 : 3 mixture of the α- and β-anomers.
Reaction of this mixture with tetra-n-butylammonium
fluoride (TBAF) resulted in removal of the TBDPS group
and the ensuing material was immediately subjected to
exhaustive acetylation under standard conditions. The
resulting triacetates (13) (40%) and (14) (47%) could be
CHO
CHO
HO
HO
HO
H
H
HO
HO
H
H
OH
OH
H
H
H
OH
OH
OH
OH
OH
H
Cl
(1)
(2)
(3)
For sometime now, we have been engaged in a program
directed toward the synthesis of novel and/or rare
carbohydrates from non-carbohydrate precursors. Two types
of precursors have been exploited in this work, namely ring-
fused gem-dibromocyclopropanes[24] and 3-halo-cis-1,2-
dihydrocatechols (2).[25]* Both types of compound are
available in either enantiomeric form, the first by resolution
of the racemate, and the second through whole-cell
biotransformation of the corresponding aromatic. A key
chemical step in the elaboration of each of these precursors
to the target carbohydrate is the ozonolytic cleavage of the
appropriate halocycloalkene followed by reductive workup, a
strategy pioneered by Hudlicky and coworkers in their
seminal studies on the conversion of 3-halo-cis-1,2-
dihydrocatechols (2) into various aldohexoses, particularly
derivatives of D-mannose (3).[26,27]† As part of our efforts in
this general area we now report on the preparation of a range
of previously unreported and differentially protected D-
talose derivatives from compound (2) (X = Cl). The relative
ease of access to such compounds afforded by the present
work should assist in general investigations into the chemical
and biological properties of this rare type of D-aldohexose.
2
Further, since H, 13C and/or 17O-labelled cis-1,2-dihydro-
catechols are rather easily produced, the correspondingly
labelled D-talose derivatives will also be readily available by
the pathway described here.‡
Results and Discussion
The elaboration of the cis-1,2-dihydrocatechol (2) into
various D-talose derivatives is shown in Scheme 1. In
keeping with earlier work[25d] on its iodo-congener,
chlorodiol (2) was selectively mono-protected at the less
sterically hindered hydroxy group using tert-
butyldiphenylsilyl chloride (TBDPS-Cl) so as to give the
mono-ol (4) together with small amounts of its regio-isomer.
This unstable mixture was immediately O-acetylated under
standard conditions to afford the differentially protected cis-
1,2-dihydrocatechol (5) [78% from (2)] which could be
readily separated from its co-produced regioisomer [16%
*
For an excellent overview on the production and synthetic utility of cis-1,2-dihydrocatechols see reference 26.
For a very useful review on the synthesis of monosaccharides from non-carbohydrate sources see reference 27b.
For useful discussions on the value of carbohydrates incorporating such labels see reference 25d.
†
‡

A Chemoenzymatic Synthesis of Differentially Protected D-Talose Derivatives
97
HO(CH2)4 OH
O
O
(2)
OTBDPS
OAc
OTBDPS
OAc
TBDPS-Cl
Cl
(6)
+
Cl
OTBDPS
H3O+
(8)
+
m-CPBA
OR
O
OH
OTBDPS
OAc
Cl
HO
OTBDPS
(4) R = H
(5) R = OAc
Ac2O,
pyridine
OAc
Cl
Cl
(7)
(9)
(i) O3 then NaI
(ii) NaBH4
OH
O
O
O
2,2-DMP,
p-TsOH
diisoamyl-
borane
O
O
O
HO
O
O
O
OH
H
H
H
AcO
OTBDPS
AcO
OTBDPS
AcO
OTBDPS
(12)
(11)
(10)
(i) TBAF
(ii) Ac2O, pyridine
O
O
O
O
AcO
AcO
+
O
O
H
H
AcO
OAc
AcO
OAc
(13)
(14)
Scheme 1
separated by flash chromatography on silica, and the
structure of the former was confirmed by single-crystal X-
ray analysis (see Fig. 2, Tables 3, 4 and Experimental
Section).
Two of these three compounds were presumed to correspond
to the α-forms of penta-O-acetyl-D-talopyranose, (15) and
(16), respectively, while the remaining material was thought
to be the isomeric β-penta-O-acetyl-D-talofuranose based
on, amongst other things, the 1H nuclear magnetic resonance
(NMR) chemical shift (δ 6.42) and coupling (d, J 4.5 Hz)
observed for the anomeric proton in this material. Support
for these conclusions came from the preparation of authentic
samples of compounds (15) and (16) from D-talose itself.
Thus, such studies established that the two-component
fraction contained a ca. 2 : 1 mixture of the penta-O-acetyl-
β-D-talofuranose and compound (15) whilst the more mobile
fraction contained pure samples of compound (16).
Efforts were made to chemically correlate triacetates (13)
and (14) with known derivatives of D-talose. Thus, a mixture
of these compounds was subjected to reaction with aqueous
trifluoroacetic acid so as to effect global deprotection and
thereby generate D-talose itself (Scheme 2). The crude
product obtained by this means was then exhaustively
acetylated with acetic anhydride in the presence of pyridine.
Thin-layer chromatography (TLC) analysis of the resulting
material revealed the presence of at least three fractions with
two able to be isolated by flash chromatographic techniques.
One fraction (the less mobile) contained a ca. 2 : 1 mixture of
two penta-O-acetates (53% combined yield), whilst the other
provided a single compound (22%) of the same composition.
Conclusions
The concise and chemoenzymatic nature of the routes to the
D-talose derivatives described above offer a rather flexible

98
M. G. Banwell et al.
Table 2. Bond angles (degrees) for (7), C24H27ClO4Si
Atom Atom Atom Angle Atom Atom Atom Angle
O8
O8
Si12 C11 108.17(16) O9
Si12 C21 110.33(17) O9
C7
C7
O10 126.2(6)
C8
C8
111.2(6)
122.6(8)
C11 Si12 C21 109.43(18) O10 C7
O8
Si12 C31 104.46(19) Si12 C11 C12 120.1(3)
C11 Si12 C31 114.93(19) Si12 C11 C16 122.0(3)
C21 Si12 C31 109.38(19) C12 C11 C16 117.4(4)
C1
Si12 O8
O7
C6
C2
C7
C2
C6
C6
C1
C3
C3
C2
C4
C4
C3
C5
C5
C6
C1
C5
C5
61.5(3)
C11 C12 C13 121.3(4)
C12 C13 C14 119.7(4)
C13 C14 C15 119.7(4)
C14 C15 C16 120.4(5)
C11 C16 C15 121.5(4)
Si12 C21 C22 121.5(3)
Si12 C21 C26 121.5(3)
C22 C21 C26 116.9(4)
C21 C22 C23 121.9(5)
C22 C23 C24 119.3(5)
C23 C24 C25 120.0(4)
C24 C25 C26 120.9(5)
C21 C26 C25 121.0(5)
Si12 C31 C32 112.4(3)
Si12 C31 C33 109.7(4)
C32 C31 C33 108.2(5)
Si12 C31 C34 108.3(3)
C32 C31 C34 106.1(5)
C33 C31 C34 112.3(6)
123.6(2)
115.4(5)
118.8(5)
59.2(3)
C3
O7
O7
C2
O8
O8
C1
O9
O9
C2
O9
C1
C1
C1
C2
C2
C2
C3
C3
C3
119.5(5)
113.1(4)
107.9(4)
114.3(4)
108.3(3)
106.2(4)
110.6(5)
112.4(6)
124.3(5)
123.3(5)
120.4(5)
59.3(3)
Cl1 C4
Cl1 C4
Fig. 1. ADEP (with 50% probability ellipsoids) of compound (7)
derived from X-ray crystallographic data.
C3
C4
O7
O7
C1
C4
C5
C6
C6
C6
118.7(6)
120.2(6)
entry into this rare class of carbohydrate that should facilitate
further studies in the appropriate areas of glycobiology and
molecular recognition.
recorded at 70 eV on either a VG Micromass 7070F mass spectrometer
or a JEOL AX-505H mass spectrometer. High-resolution mass spectra
were recorded with a VG Micromass 7070F instrument. Optical
rotations were measured at 20°C with a Perkin–Elmer 241 polarimeter
at the sodium D-line (589 nm) using spectroscopic grade chloroform
(Merck) and at the concentration (c) (g/100 mL) indicated. The
measurements were carried out in a cell with a path length of 1 dm.
Specific rotations ([α]D20 ) were calculated using the equation
[α]D = (100.α)/(c.1) and are given in units of 10–1.deg.cm2.g–1. THF
was distilled, under nitrogen, from sodium benzophenone ketyl.
Dichloromethane was distilled from calcium hydride and methanol
from magnesium methoxide.
Experimental
Melting points were recorded with a Kofler hot stage apparatus and are
uncorrected. Proton (1H) and carbon (13C) NMR spectra were recorded
with a Varian Unity 300 or Varian Gemini 300 spectrometer operating
at 300 MHz for proton and 75 MHz for carbon. All such spectra were
recorded in deuteriochloroform (CDCl3) solution at 22°C. The degree
of protonation of each carbon atom observed in the 13C NMR spectra
was determined by attached proton test (APT) experiments. Infrared
(IR) spectra (νmax) were recorded with either a Perkin–Elmer 983G
infrared spectrophotometer or a Perkin–Elmer 1800 Series FTIR
instrument. Samples were analysed either as thin films on sodium
chloride plates (for liquids) or as potassium bromide disks (for solids).
Low-resolution electron-impact mass spectra (LREI-MS) (m/z) were
(1S,6S)-2-Chloro-6-{[(1,1-dimethylethyl)diphenylsilyl]oxy}-2,4-cyclo-
hexadien-1-ol (4) and (1S,2S)-3-Chloro-2-{[(1,1-dimethylethyl)di-
phenylsilyl]oxy}-3,5-cyclohexadien-1-ol
Table 1. Bond lengths (Å) for (7), C24H27ClO4Si
A magnetically stirred solution of compound (2) (17.0 g, 116.0 mmol)
and imidazole (21.0 g, 308.5 mmol) in dichloromethane (100 mL)
maintained at 18°C under a nitrogen atmosphere was treated, dropwise
over a period of 0.5 h, with TBDPS-Cl (Aldrich, 32.5 mL, 124.2 mmol).
The ensuing mixture was stirred for a further 1.0 h then diluted with
water (500 mL) and extracted with dichloromethane (3 × 150 mL). The
combined organic phases were washed with brine (2 × 150 mL) then
dried (MgSO4), filtered and concentrated under reduced pressure to
give a ca. 4 : 1 mixture (as judged by 1H NMR analysis) of the title
Atom
Atom
Distance
Atom
Atom
Distance
Cl1
Si12
Si12
Si12
Si12
O7
O7
O8
O9
O9
O10
C1
C1
C2
C3
C4
O8
C11
C21
C31
C1
C6
C2
C3
C7
C7
C2
C6
C3
C4
C5
C6
1.733(6)
1.651(3)
1.881(4)
1.881(4)
1.889(4)
1.416(6)
1.414(7)
1.435(5)
1.455(6)
1.333(9)
1.182(8)
1.476(7)
1.448(7)
1.539(6)
1.532(8)
1.346(9)
1.404(9)
C7
C8
1.526(9)
1.398(6)
1.386(6)
1.381(6)
1.401(7)
1.357(7)
1.391(6)
1.382(6)
1.398(6)
1.395(7)
1.374(8)
1.355(7)
1.381(7)
1.534(7)
1.536(8)
1.516(7)
C11
C11
C12
C13
C14
C15
C21
C21
C22
C23
C24
C25
C31
C31
C31
C12
C16
C13
C14
C15
C16
C22
C26
C23
C24
C25
C26
C32
C33
C34
compounds as
a clear colourless oil. Since this material was
exceptionally prone to decomposition it was used immediately in the
next step of the reaction sequence.
(1S,6S)-2-Chloro-6-{[(1,1-dimethylethyl)diphenylsilyl]oxy}-2,4-cyclo-
hexadien-1-ol Acetate (5) and (1S,6S)-5-Chloro-6-{[(1,1-dimethyl-
ethyl)diphenylsilyl]oxy}-2,4-cyclohexadien-1-ol Acetate
The 4 : 1 mixture of compound (4) and its regio-isomer (44.65 g,
116.0 mmol), obtained as described immediately above, was dissolved
in pyridine (30 mL) and the resulting solution treated with acetic
anhydride (22 mL, 233.2 mmol) and 4-dimethylaminopyridine
(DMAP) (1.40 g, 11.6 mmol) while being stirred magnetically and
C4
C5

A Chemoenzymatic Synthesis of Differentially Protected D-Talose Derivatives
99
Table 4. Bond angles (degrees) for (13), C15H22O9
Atom Atom Atom Angle Atom Atom Atom Angle
C2
C2
C3
C4
C6
C7
O1
O1
O8
O12
O12
C2
O16
O16
C3
O1
O8
O12
O16
O20
O21
C2
C2
C2
C3
C3
C3
C4
C4
C4
C5
C5
C5
C6
C5
C9
C13
C17
C22
C22
O8
C3
C3
C2
C4
C4
C3
C5
C5
C4
C6
C6
C5
110.0(2) O20
115.4(3) C5
118.2(3) O21
115.8(3) O8
108.8(2) O8
105.7(3) O10
110.2(2) O12
106.2(3) O12
106.3(3) O14
105.1(3) O16
108.7(3) O16
100.5(3) O18
113.7(2) O20
109.2(3) O20
101.9(3) O21
103.9(3) O20
110.7(2) O21
115.5(3) C23
112.0(3)
C6
C6
C7
C9
C9
C9
C13
C13
C13
C17
C17
C17
C22
C22
C22
C22
C22
C22
C7
C7
C6
104.3(2)
114.5(3)
103.5(3)
122.5(3)
111.0(3)
126.5(3)
123.7(4)
109.7(3)
126.6(3)
123.4(3)
111.9(3)
124.7(4)
104.5(3)
110.0(3)
111.5(3)
108.7(3)
109.1(3)
112.7(3)
O10
C11
C11
O14
C15
C15
O18
C19
C19
O21
C23
C23
C24
C24
C24
O1
O1
C4
O20
426.1421. C24H2735ClO3Si requires M+•, 426.1418). H NMR (CDCl3,
300 MHz) δ 7.75–7.70, complex m, 4H; 7.50–7.38, complex m, 6H;
6.17, d, J 5.9 Hz, 1H; 5.75, ddd, J 9.0, 5.9 and 2.4 Hz, 1H; 5.61, dd, J
9.0 and 2.4 Hz, 1H; 5.56, d, J 6.6 Hz, 1H; 4.72, dt, J 6.6 and 2.4 Hz, 1H;
2.15, s, 3H; 1.09, s, 9H. 13C NMR (CDCl3, 75 MHz) δ 170.2, 136.0,
135.9, 133.7, 132.8, 130.7, 130.4, 130.1, 130.1, 127.9(1), 127.8(7),
125.3, 121.9, 71.1, 70.5, 26.9, 21.0, 19.2. νmax (KBr) 2958, 2932, 2858,
1747, 1427, 1226, 112, 868, 821, 702 cm–1. EI MS m/z (70 eV) 428 and
426 (M+•, both < 1%), 384 (< 1) and 386 (< 1), 368 (< 1) and 366 (2),
84 (100).
1
Fig. 2. ADEP (with 50% probability ellipsoids) of compound (13)
derived from X-ray crystallographic data.
Table 3. Bond lengths (Å) for (13), C15H22O9
Atom
Atom
Distance
Atom
Atom
Distance
O1
O1
O8
O8
O10
O12
O12
O14
O16
O16
O18
O20
O20
C2
C5
C2
C9
C9
C3
C13
C13
C4
C17
C17
C6
1.415(4)
1.451(4)
1.439(4)
1.373(4)
1.195(4)
1.447(4)
1.343(4)
1.193(5)
1.442(4)
1.356(4)
1.191(5)
1.428(4)
1.449(4)
O21
O21
C2
C3
C4
C5
C6
C9
C13
C17
C22
C22
C7
C22
C3
C4
C5
1.430(4)
1.423(4)
1.503(4)
1.518(5)
1.519(5)
1.515(4)
1.525(5)
1.491(5)
1.495(5)
1.492(5)
1.516(4)
1.502(5)
Concentration of fraction B (RF 0.4) afforded (1S,6S)-5-chloro-6-
{[(1,1-dimethylethyl)diphenylsilyl]oxy}-2,4-cyclohexadien-1-ol ace-
tate (7.90 g, 16%) as a clear colourless oil, [α]D +5.3 (c, 1.03) (Found:
M+•, 426.1417. C24H2735ClO3Si requires M+•, 426.1418). 1H NMR
(CDCl3, 300 MHz) δ 7.77–7.70, complex m, 4H; 7.45–7.37, complex
m, 6H; 6.18, d, J 5.2 Hz, 1H; 5.95, ddd, J 9.7, 5.7 and 3.1 Hz, 1H; 5.81,
ddm, J 9.7 and 3.1 Hz, 1H; 5.28, m, 1H; 4.26, d, J 5.7 Hz, 1H; 1.77, s,
3H; 1.08, s, 9H. 13C NMR (CDCl3, 75 MHz) δ 170.2, 136.2, 136.2,
135.3, 133.6, 132.7, 130.0, 129.8, 127.7, 127.5, 126.1, 124.0, 123.3,
72.5, 71.4, 26.9, 20.9, 19.9. νmax (KBr) 2931, 2857, 1738, 1427, 1369,
1233, 1112, 1049, 702, 505 cm–1. EI-MS m/z (70 eV) 428 and 426 (M+•,
both < 1%), 384 (< 1) and 386 (< 1), 311 (33) and 309 (63), 293 (45)
and 291 (80), 241 (87), 199 (100).
C6
C7
C11
C15
C19
C23
C24
C22
[1S-(1α,2α,3α,6α)]-4-Chloro-2-{[(1,1-dimethylethyl)diphenylsilyl]-
oxy}-7-oxabicylco[4.1.0]hept-4-en-3-ol Acetate (6) and [1R-(1α,2β,-
3β,6α)]-4-Chloro-2-{[(1,1-dimethylethyl)diphenylsilyl]oxy}-7-oxa-
bicyclo[4.1.0]hept-4-en-3-ol Acetate (7)
maintained at 18°C under a nitrogen atmosphere. After 2 h the reaction
mixture was concentrated under reduced pressure and the residue
subjected to flash chromatography (silica gel, gradient elution using
1.25 to 1.5% v/v hexane/ethyl acetate) thereby affording two fractions,
A and B.
A magnetically stirred solution of compound (5) (2.08 g, 4.87 mmol) in
dichloromethane (25 mL) maintained at 0–5°C (ice bath) under a
nitrogen atmosphere was treated, in one portion, with m-CPBA
(technical grade, Aldrich, ca. 70% peracid, 1.26 g, 5.11 mmol peracid).
Concentration of fraction A (RF 0.5) afforded compound (5) (38.54
g, 78%) as a clear colourless oil, [α]D –107.4 (c, 1.75) (Found: M+•,
AcO
O
OAc
Ac2O, pyridine
(13)
O
OAc
OAc
AcO
AcO
(i) TFA/H2O
AcO
AcO
+
(1)
+
H
(ii) Ac2O, pyridine
(14)
OAc
(15)
OAc
(16)
Scheme 2

100
M. G. Banwell et al.
Stirring was continued overnight during which time the ice bath and
reaction mixture were allowed to warm to ca. 18°C. The resulting
mixture was then washed with sodium metabisulfite (3 × 60 mL of an
15% w/v aqueous solution), sodium bicarbonate (1 × 60 mL of a
saturated aqueous solution) and water (1 × 60 mL) before being dried
(MgSO4), filtered and concentrated under reduced pressure. The
ensuing light-yellow oil was subjected to flash chromatography (silica
gel, gradient elution using 2–3% v/v ethyl acetate/hexane) thereby
affording two fractions, A and B.
129.8, 128.5, 128.0, 127.5, 74.4, 72.3, 70.8, 70.4, 27.0, 20.5, 19.8. νmax
(KBr) 3429, 2931, 2857, 1747, 1227, 1159, 1112, 1040, 738, 703, 508
• +
cm–1. EI-MS m/z (70 eV) 405 (2%) and 403 (7) [M – C4H9 ] , 267 (20)
and 265 (50), 241 (60), 199 (100), 181 (60).
(1S,2S,3S,6R)-4,6-Dichloro-2-{[(1,1-dimethylethyl)diphenylsilyl]-
oxy}-4-cyclohexene-1,3-diol 3-Acetate and (1R,2S,3S,4S)-5-Chloro-3-
{[(1,1-dimethylethyl)diphenylsilyl]oxy}-5-cyclohexene-1,2,4-triol 4-
Acetate (9)
Concentration of fraction A (RF 0.5) afforded compound (6) (1.25 g,
58%) as a clear colourless oil, [α]D +34.6 (c, 1.1) (Found: M+•,
442.1363. C24H2735ClO4Si requires M+•, 442.1367). 1H NMR (CDCl3,
300 MHz) δ 7.75–7.65, complex m, 4H; 7.50–7.40, complex m, 6H;
6.30, dd, J 4.1 and 2.2 Hz, 1H; 5.38, m 1H; 4.55, m, 1H; 3.41, m 1H;
3.35, m, 1H; 1.94, s, 3H; 1.11, s, 9H. 13C NMR (CDCl3, 75 MHz) δ
170.1, 136.5, 136.3, 135.9, 133.6, 133.3, 130.7, 130.5, 128.4, 128.1,
122.8, 69.4, 68.4, 53.7, 48.6, 27.3, 21.0, 20.0; νmax (KBr) 2957, 2858,
2932, 1751, 1369, 1225, 1112, 703, 506 cm–1. EI-MS m/z (70 eV) 444
and 442 (M+•, both < 1%), 241 (100), 199 (80).
A solution of compound (7) (457 mg, 1.03 mmol) and water (2 mL) in
THF (6 mL) was treated with HCl (1 mL of a 1 M aqueous solution) and
the ensuing mixture allowed to stand at 18°C for 24 h and then treated
with NaOH (2.5 mL of a 1 M aqueous solution) and dichloromethane
(10 mL). The separated aqueous phase was extracted with
dichloromethane (3 × 8 mL) and the combined organic phases were
washed with brine (1 × 10 mL) then dried (MgSO4), filtered and
concentrated under reduced pressure to give a light-yellow oil.
Subjection of this material to flash chromatography (silica gel, gradient
elution using 3 to 30% v/v ethyl acetate/hexane) afforded three
fractions, A–C.
Concentration of fraction B (RF 0.3) afforded compound (7) (0.38 g,
18%) as a white crystalline solid, melting point (m.p.) 156–158°C, [α]D
Concentration of fraction A (RF 0.6 in 1 : 2.5 : 5.5 v/v/v ethyl
acetate/dichloromethane/hexane) afforded starting material (7) (68 mg,
15% recovery), identical, in all respects, with authentic material.
Concentration of fraction B (RF 0.5 in 1 : 2.5 : 5.5 v/v/v ethyl acetate/
dichloromethane/hexane) afforded (1S,2S,3S,6R)-4,6-dichloro-2-
{[(1,1-dimethylethyl)diphenylsilyl]oxy}-4-cyclohexene-1,3-diol 3-ace-
tate (231 mg, 47 at 85% conversion) as a white crystalline solid, m.p.
135.5–137°C, [α]D –131.4 (c, 0.9) (Found: C, 59.6; H, 5.8; Cl, 14.7%;
• +
–156.9 (c, 1.1) (Found: C, 64.8; H, 6.1; Cl, 7.9%; [M – C4H9 ] ,
385.0663. C24H2735ClO4Si requires C, 65.1, H, 6.1, Cl, 8.0%; [M –
C4H9• ]+, 385.0663). 1H NMR (CDCl3, 300 MHz) δ 7.81, m, 2H; 7.77,
m, 2H; 7.50–7.37, complex m, 6H; 6.25, d, J 4.4 Hz, 1H; 5.86, dd, J 5.7
and 1.9 Hz, 1H; 4.31, dd, J 5.7 and 1.2 Hz, 1H; 3.17, t, J 4.2 Hz, 1H;
3.03, m, 1H; 2.24, s, 3H; 1.09, s, 9H. 13C NMR (CDCl3, 75 MHz) δ
170.7, 135.9, 135.8, 134.9, 134.7, 133.3, 132.1, 130.3, 130.2, 129.6,
128.1, 128.0, 127.7, 126.7, 70.6, 70.0, 54.9, 47.8, 26.7, 21.2, 19.2. νmax
(KBr) 2931, 2858, 1743, 1427, 1370, 1233, 1112, 706, 507 cm–1. EI-
MS m/z (70 eV) 444 and 442 (M+•, both < 1%), 241 (53), 199 (100).
• +
[M – C4H9 ] , 421.0427. C24H2835Cl2O4Si requires C, 60.1; H, 5.9; Cl,
• +
14.8%; [M – C4H9 ] , 421.0430). 1H NMR (CDCl3, 300 MHz) δ 7.75–
7.65, complex m, 4H; 7.50–7.38, complex m, 6H; 6.07, d, J 4.4 Hz, 1H;
5.70, d, J 4.4 Hz, 1H; 4.56, br t, J 4.4 Hz, 1H; 4.37, m, 1H; 3.72, m, 1H;
2.70, br s, 1H; 1.98, s, 3H; 1.09, s, 9H. 13C NMR (CDCl3, 75 MHz) δ
169.5, 136.1, 136.0, 132.6, 132.5, 130.4, 130.2, 128.1, 127.9, 126.8,
73.4, 70.2, 69.2, 56.6, 27.0, 20.7, 19.5 (one signal obscured or
overlapping). νmax (KBr) 2932, 2858, 1751, 1226, 1113, 1048,
736, 702, 508 cm–1. EI-MS m/z (70 eV) 425 (< 1%), 423 (2) and 421
(1S,2S,3S,6R)-4-Chloro-2-{[(1,1-dimethylethyl)diphenylsilyl]oxy}-6-
(4´-hydroxybutoxy)-4-cyclohexene-1,3-diol 3-Acetate (8) and (1R,2S,-
3S,4S)-5-Chloro-3-{[(1,1-dimethylethyl)diphenylsilyl]oxy}-5-cyclo-
hexene-1,2,4-triol 4-Acetate (9)
A magnetically stirred solution of epoxide (7) (1.08 g, 2.44 mmol) in
THF (15 mL) and water (5 mL) was treated with phosphoric acid
(0.5 mL of a 93% aqueous solution, M & B) whilst being maintained
under a nitrogen atmosphere. The resulting mixture was stirred at 18°C
for 40 h then concentrated under reduced pressure and the residue
partitioned between ethyl acetate (30 mL) and brine (30 mL). The
separated aqueous phase was extracted with ethyl acetate (3 × 30 mL)
and the combined organic phases were then dried (MgSO4), filtered and
concentrated under reduced pressure. The resulting light-yellow oil was
subject to flash chromatography (silica gel, gradient elution using 30 to
50% v/v ethyl acetate/hexane) thereby affording two fractions, A and B.
Concentration of fraction A (RF 0.5 in 8 : 2.5 : 5.5 v/v/v ethyl
acetate/dichloromethane/hexane) then afforded compound (8) (265 mg,
• +
(4) [M – C4H9 ] , 250 (35) and 248 (78), 241 (88), 199 (100).
Concentration of fraction C (RF 0.7 in 8 : 2.5 : 5.5 v/v/v ethyl acetate/
dichloromethane/hexane) afforded diol (9) (50 mg, 10 at 85%
conversion), identical, in all respects, with material obtained as
described immediately above.
3-O-[(1,1-Dimethylethyl)diphenylsilyl]-D-talonic acid γ-Lactone 2-
Acetate (10)
A magnetically stirred solution of diol (9) (830 mg, 1.80 mmol) and
pyridine (2 mL) in methanol (35 mL) was cooled to –78°C (acetone/
dry-ice bath) then treated with a stream of ca. 40% ozone in oxygen
(produced by a Wallace & Tiernan ozonator) for 1.0 h, at which point
TLC analysis indicated the complete consumption of the starting
material. The reaction mixture was purged with nitrogen and then
treated with sodium iodide (840 mg, 5.60 mmol). After 3 h the now red-
brown reaction mixture was warmed to –66°C and treated with sodium
borohydride (1.35 g, 35.69 mmol). The reaction mixture was
maintained between –60 and –40°C for 6 h and then treated with
sufficient 2 M HCl in methanol so as to reduce the pH to ca. 3.5. The
ensuing mixture was concentrated under reduced pressure and the
residue partitioned between ethyl acetate (25 mL) and brine (25 mL).
The separated aqueous phase was extracted with ethyl acetate
(3 × 20 mL) and the combined organic phases were dried (MgSO4),
filtered and concentrated under reduced pressure. Subjection of the
resulting light-yellow oil to flash chromatography (silica gel, 60% v/v
ethyl acetate/hexane elution) and concentration of the appropriate
fractions (RF 0.4) then afforded lactone (10) (450 mg, 54%) as a clear,
• +
20%) as a light-yellow oil, [α]D –87.2 (c, 1.0) (Found: [M – C4H9 ] ,
• +
475.1345. C28H3735ClO6Si requires [M – C4H9 ] , 475.1344). 1H NMR
(CDCl3, 300 MHz) δ 7.75–7.70, complex m, 4H; 7.45–7.38, complex
m, 6H; 6.07, br d, J 4.0 Hz, 1H; 5.61, br d, J 4.0 Hz, 1H; 4.28, m, 1H;
4.03, br, t, J 4.0 Hz, 1H; 3.64–3.54, complex m, 3H; 3.41, m, 1H; 3.25,
m, 1H; 2.43, s, 2H; 1.88, s, 3H; 1.52, m, 4H; 1.08, s, 9H. 13C NMR
(CDCl3, 75 MHz) δ 169.8, 136.1, 136.0, 132.9, 132.8, 131.7, 130.2,
129.9, 127.9, 127.7, 126.5, 77.4, 70.8, 70.5, 69.9, 62.5, 29.5, 26.9, 26.5,
20.7, 19.5 (one signal obscured or overlapping). νmax (KBr) 3429, 2932,
2858, 1747, 1370, 1228, 1112, 1045, 740, 704, 507 cm–1. EI-MS m/z
• +
(70 eV) 477 (1%) and 475 (2) [M – C4H9 ] , 241 (78), 199 (100), 181
(52), 101 (90).
Concentration of fraction B (RF 0.7 in 8 : 2.5 : 5.5 v/v/v ethyl acetate/
dichloromethane/hexane) then afforded compound (9) (795 mg, 71%)
• +
as a clear, colourless oil, [α]D –59.1 (c, 1.0) (Found: [M – C4H9 ] ,
• +
1
• +
403.0763. C24H2935ClO5Si requires[M– C4H9 ] , 403.0769). H NMR
(CDCl3, 300 MHz) δ 7.75–7.65, complex m, 4H; 7.50–7.38, complex
m, 6H; 6.02, m 1H; 5.48, m, 1H; 4.50, m, 1H; 4.30, m, 1H; 3.51, dd, J
6.5 and 1.6 Hz, 1H; 2.74, s, 2H; 1.69, s, 3H; 1.08, s, 9H. 13C NMR
(CDCl3, 75 MHz) δ 170.0, 136.2, 136.1, 132.9, 132.5, 130.9, 130.3,
colourless oil, [α]D +19.1 (c, 0.6) (Found: [M – C4H9 ] , 401.1041.
• +
1
C24H30O7Si requires [M – C4H9 ] , 401.1057). H NMR (CDCl3, 300
MHz) δ 7.62–7.58, complex m, 4H; 7.50–7.37, complex m, 6H; 5.62,
d, J 5.6 Hz, 1H; 4.61, d, J 5.6 Hz, 1H; 4.13, br s, 1H; 3.42, dd, J 11.3
and 8.0 Hz, 1H; 3.31, dd, J 11.3 and 4.1 Hz, 1H; 3.15, m, 1H; 2.55, br

A Chemoenzymatic Synthesis of Differentially Protected D-Talose Derivatives
101
s, 2H; 2.10, s, 3H; 1.07, s, 9H. 13C NMR (CDCl3, 75 MHz) δ 172.8,
170.2, 135.8, 135.7, 132.9, 132.2, 130.5, 130.5, 128.2, 128.1, 86.3,
71.8, 70.5, 69.2, 63.1, 26.8, 20.6, 19.4. νmax (KBr) 3467, 2930, 2857,
1796, 1753, 1375, 1232, 1113, 1104, 703, 508 cm–1. EI-MS m/z (70 eV)
ammonium chloride (20 mL of a saturated aqueous solution) and ethyl
acetate (15 mL). The separated aqueous phase was extracted with
ethyl acetate (2 × 10 mL) and the combined organic phases were
washed with brine (1 × 15 mL) and then dried (MgSO4), filtered and
concentrated under reduced pressure to give a light-yellow oil.
Subjection of this material to flash chromatography (silica gel, gradient
elution using 20 to 25% v/v ethyl acetate/hexane) afforded two
fractions, A and B.
• +
401 [M – C4H9 ] (15%), 199 (100).
3-O-[(1,1-Dimethylethyl)diphenylsilyl]-5,6-O-(1-methylethylidene)-D-
talonic Acid γ-Lactone 2-Acetate (11)
Concentration of fraction A (RF 0.5 in 4 : 2.5 : 5.5 v/v/v ethyl
acetate/dichloromethane/hexane) afforded compound (13) (18 mg,
40%) as a light-yellow and crystalline solid, m.p. 96–98°C, [α]D +11.2
A
solution of compound (10) (100 mg, 0.22 mmol) in
2,2-dimethoxypropane (7 mL) was treated with p-toluenesulfonic
acid (25 mg, 0.13 mmol) and the resulting mixture stirred at 18°C
for 3 h, treated with triethylamine (2 mL) and then concentrated
under reduced pressure. Then residue thus obtained was subject to
flash chromatography (silica gel, 15% v/v ethyl acetate/hexane
elution) and concentration of the appropriate fractions (RF 0.4)
then afforded compound (11) (90 mg, 82%) as a white crystalline solid,
m.p. 106–107.5°C, [α]D +16.0 (c, 1.0) (Found: C, 63.2; H, 6.5%; [M –
• +
(c, 0.25) (Found: C, 52.0; H, 6.1%; [M – CH3 ] , 331.1029. C15H22O9
• +
1
requires C, 52.0; H, 6.4%; [M – CH3 ] , 331.1030). H NMR (CDCl3,
300 MHz) δ 6.43, d, J 4.5 Hz, 1H; 5.34, dd, J 5.9 and 2.1 Hz, 1H; 5.28,
m, 1H; 4.30, m, 1H; 4.24, m, 1H; 4.02, t, J 6.7 Hz, 1H; 3.91, m, 1H;
2.13, s, 3H; 2.11, s, 3H; 2.07, s, 3H; 1.39, s, 3H; 1.36, s, 3H. 13C NMR
(CDCl3, 75 MHz) δ 170.3, 169.7, 169.3, 110.1, 94.4, 83.2, 75.3, 71.1,
70.3, 65.2, 26.2, 25.8, 21.3, 21.0, 20.6. νmax (KBr) 2988, 2925, 1750,
1372, 1222, 1111, 1065, 1011, 939 cm–1. EI-MS m/z (70 eV) 331 [M –
• +
C4H9•]+, 441.1371. C27H34O7Si requires C, 65.0; H, 6.9%; [M –
C4H9 ] , 441.1370). 1H NMR (CDCl3, 300 MHz) δ 7.70–7.60,
complex m, 4H; 7.55–7.38, complex m, 6H; 5.58, d, J 5.5 Hz, 1H; 4.62,
d, J 5.5 Hz, 1H; 4.06, s, 1H; 3.72, m, 2H; 3.45, t, J 7.3 Hz, 1H; 2.15, s,
3H; 1.25, s, 3H; 1.23, s, 3H; 1.07, s, 9H. 13C NMR (CDCl3, 75 MHz) δ
172.3, 169.9, 135.9, 135.7, 132.9, 132.1, 130.5, 128.2, 128.1, 110.6,
83.6, 74.2, 71.9, 69.2, 65.2, 26.7, 25.6, 25.5, 20.6, 19.4 (one signal
obscured or overlapping). νmax (KBr) 2933, 2859, 1803, 1752, 1373,
1225, 1137, 1113, 1096, 703, 507 cm–1. EI-MS m/z (70 eV) 483 [M –
• +
CH3 ] , (80%), 287 (15), 169 (60), 127 (29), 101 (100).
Concentration of fraction B (RF 0.4 in 4 : 2.5 : 5.5 v/v/v ethyl acetate/
dichloromethane/hexane) afforded compound (14) (22 mg, 47%) as a
• +
clear colourless oil, [α]D –54.0 (c, 0.25) (Found: [M – CH3 ] ,
• +
331.1029. C15H22O9 requires [M – CH3 ] , 331.1030). 1H NMR
(CDCl3, 300 MHz) δ 6.18, d, J 1.8 Hz, 1H; 5.44–5.32, complex m, 2H;
4.26–4.14, complex m, 2H; 4.03, m, 1H; 3.84, m, 1H; 2.12, s, 3H; 2.09,
s, 3H; 2.08, s, 3H; 1.40, s, 3H; 1.38, s, 3H. 13C NMR (CDCl3, 75 MHz)
δ 169.7, 169.4, 169.2, 110.0, 98.1, 80.9, 75.3, 74.3, 71.1, 65.2, 26.3,
25.8, 21.3, 20.8, 20.8. νmax (KBr) 2988, 2925, 1752, 1372, 1219, 1062,
• +
• +
CH3 ] , (30%), 441 [M – C4H9 ] , (33), 383 (100), 341 (50), 241 (80),
199 (94).
• +
3-O-[(1,1-Dimethylethyl)diphenylsilyl]-5,6-O-(1-Methylethylidene)-
970 cm–1. EI-MS m/z (70 eV) 331 [M – CH3 ] , (53%), 287 (12), 169
D-talo-furanose 3-Acetate (12)
(57), 127 (40), 101 (100).
Method B. A magnetically stirred solution of compound (12)
(51 mg, 0.10 mmol) and DMAP (15 mg, 0.12 mmol) in pyridine
(2.5 mL) maintained under a nitrogen atmosphere at 18°C was treated
with acetic anhydride (0.5 mL). After 3 h the reaction mixture was
treated with dichloromethane (8 mL) and ammonium chloride (15 mL
of a saturated aqueous solution). The separated organic phase was
washed with ammonium chloride (15 mL of a saturated aqueous
solution) and brine (1 × 15 mL) and then dried (MgSO4), filtered and
concentrated under reduced pressure to give a light-yellow oil. This
material was dissolved in THF (2.5 mL) and then treated with tetra-n-
butylammonium fluoride (90 µL of a 1 M solution in THF, 0.09 mmol).
After 0.5 h the reaction mixture was treated with pyridine (4 mL), acetic
anhydride (0.5 mL) and DMAP (6 mg, 0.05 mmol), and maintained at
18°C with stirring for 14 h. The resulting light-yellow solution was
treated with sodium bicarbonate (15 mL of a saturated aqueous
solution) and ethyl acetate (10 mL). The separated aqueous phase was
extracted with ethyl acetate (3 × 5 mL) and the combined organic
phases were washed with brine (1 × 15 mL) and then dried (MgSO4),
filtered and concentrated under reduced pressure to give a light-yellow
oil. Subjection of this material to flash chromatography (silica gel,
gradient elution using 20 to 25% v/v ethyl acetate/hexane) afforded two
fractions, A and B.
A solution of diisoamylborane in THF was prepared by treating BH3–
dimethyl sulfide complex (2 mL of a 2 M solution in THF, 4 mmol,
Aldrich) maintained at 0°C under a nitrogen atmosphere with
2-methylbut-2-ene (4 mL of a 2 M solution in THF, 8 mmol). After
stirring the ensuing mixture for 3 h at 0°C it was treated with a solution
of lactone (11) (231 mg, 0.46 mmol) in THF (5 mL). After 3 days at
18°C, the reaction mixture was quenched with water (1 mL) and sodium
bicarbonate (10 mL of a saturated aqueous solution) added. This was
followed by the addition of hydrogen peroxide (0.5 mL of a 30%
aqueous solution) and the resulting mixture then concentrated under
reduced pressure. The residue was partitioned between water (20 mL)
and dichloromethane (20 mL) and the separated aqueous phase was
then extracted with dichloromethane (3 × 20 mL). The combined
organic phases were dried (MgSO4), filtered and concentrated under
reduced pressure to afford a light-yellow oil. Subjection of this material
to flash chromatography (silica gel, 15% v/v ethyl acetate/hexane) and
concentration of the appropriate fractions (RF 0.3) then afforded a ca.
2 : 3 mixture of the α- and β-forms of lactol (12) (192 mg, 83%) as a
• +
clear colourless oil, [α]D –30.2 (c, 0.5) (Found: [M – C4H9 ] , 443.1523.
• +
C27H36O7Si requires [M – C4H9 ] , 443.1526). 13C NMR (CDCl3,
75 MHz) δ 169.9(9), 169.9(5), 136.0, 135.9, 135.8, 135.7, 133.4, 132.6,
132.4, 131.9, 130.5, 130.3, 130.2, 128.1(3), 128.0(5), 127.9(6),
127.9(2), 109.8, 109.6, 100.0, 96.4, 83.4, 82.0, 77.5, 75.2, 74.3, 74.0,
72.6, 72.4, 66.0, 65.2, 30.1, 27.1, 27.0, 26.1, 25.7, 22.1, 21.3, 21.2,
21.0, 19.3 (one signal overlapping or obscured). νmax (KBr) 3443, 2933,
2859, 1748, 1371, 1235, 1113, 1062, 703, 505 cm–1. EI-MS m/z (70 eV)
Concentration of fraction
A (RF 0.5 in 4 : 2.5 : 5.5 v/v/v
ethyl acetate/dichloromethane/hexane) afforded compound (13)
(22 mg, 63%) identical, in all respects, with the chromatographically
more mobile product obtained by Method A as described immediately
above.
Concentration of fraction B (RF 0.4 in 4 : 2.5 : 5.5 v/v/v ethyl acetate/
dichloromethane/hexane) afforded compound (14) (6 mg, 17%)
identical, in all respects, with the chromatographically less mobile
product obtained by Method A as described immediately above.
• +
• +
485 [M – CH3 ] , (23%), 443 [M – C4H9 ] , (38), 325 (45), 341 (50),
241 (68), 199 (100), 101 (84).
5,6-O-(1-Methylethylidene)-α-D-talofuranose Triacetate (13) and
5,6-O-(1-Methylethylidene)-β-D-talofuranose Triacetate (14)
Method A. A magnetically stirred mixture of compound (12)
(67 mg, 0.13 mmol) in THF (4 mL) maintained under a nitrogen
atmosphere at 18°C was treated with tetra-n-butylammonium fluoride
(150 µL of a 1 M solution in THF, 0.15 mmol). After 0.5 h the reaction
mixture was treated with pyridine (6 mL), acetic anhydride (0.5 mL,
5.30 mmol) and DMAP (13 mg, 0.11 mmol) and then stirring continued
at 18°C for 14 h. The resulting light-yellow solution was treated with
α-Penta-O-acetyl-D-talopyranose (15) a-Penta-O-acetyl-D-talofura-
nose (16)
Method A. A magnetically stirred solution of authentic D-talose
(153 mg, 0.85 mmol) in pyridine (4 mL) was cooled to 0°C (ice-
bath) and then treated with acetic anhydride (2 mL). The resulting
solution was stirred at 0–18°C for 18 h, and then treated with

102
M. G. Banwell et al.
NaHCO3 (20 mL of a saturated aqueous solution) and ethyl acetate
(20 mL). The separated organic phase was washed with NaHCO3
(1 × 20 mL of a saturated aqueous solution), and NH4Cl (2 × 20 mL
of a saturated aqueous solution), and then dried (MgSO4), filtered
and concentrated under reduced pressure to give a light-yellow oil.
Subjection of this material to flash chromatography (silica gel,
gradient elution using 25 to 35% v/v ethyl acetate/hexane) afforded
two fractions, A and B.
Crystallography
Crystal Data
Compound (7). C24H27ClO4Si,
M
443.015,
T
200 K,
orthorhombic, space group P212121, a 9.7325(7), b 9.7726(7), c
25.180(2) Å, V 2394.9(3) Å3, Dc (Z 4) 1.229 g cm–3, F(000) 936, µ(Mo
Kα) 0.236 Å, 4063 unique data (2θmax 50.05°), 2935 with I > 3σ(I), R
0.0611, ωR 0.0704, S 1.0696.
Compound (13). C15H22O9, M 346.332, T 200 K, monoclinic,
space group C2, a 16.5808(3), b 5.73230(10), c 19.0387(5) Å, β
109.5197(9)°, V 1705.55(6) Å3, Dc (Z 4) 1.349 g cm–3, F(000) 736,
µ(Mo Kα) 0.112 Å, 2155 unique data (2θmax 54.96°), 1307 with I >
2σ(I), R 0.0349, ωR 0.0389, S 1.0604.
Concentration of fraction A (RF 0.26 in 4 : 2.5 : 5.5 v/v/v ethyl
acetate/dichloromethane/hexane) afforded compound (15) (259 mg,
78%) as light-yellow crystalline solid, m.p. 104–106°C (lit.[30] 107°C),
[α]D +74.8 (c, 0.5) (lit.[30] +70.2 in CHCl3) (Found: C, 49.3; H, 5.3%;
[M – CH3CO•]+, 347.0969. Calc. for C16H22O11: C, 49.2; H, 5.7%; [M –
1
CH3CO•]+, 347.0978). H NMR (CDCl3, 300 MHz) δ 6.08, br s, 1H;
Structure Determination
5.3, br s, 1H; 5.25, t, J 3.7 Hz, 1H; 5.25, m, 1H; 4.26, br t, J 6.9 Hz, 1H;
4.10, m, 2H; 2.10(3), s, 3H; 2.10(1), s, 3H; 2.09, s, 3H; 1.98, s, 3H; 1.95,
s, 3H. 13C NMR (CDCl3, 75 MHz) δ 170.2, 169.9, 169.5, 169.5, 167.9,
91.4, 68.8, 66.3, 65.3, 65.1, 61.5, 21.0, 20.9, 20.8, 20.7(4), 20.6(6).
Intensity data were collected using a Nonius Kappa CCD diffractometer
and extracted from diffraction images using the DENZO[31] package.
Analytical absorption corrections were applied.[32] Both structures were
solved by direct methods[33] and expanded using Fourier techniques.[34]
Full matrix least-squares refinement was on F, non-hydrogen atoms
were refined anisotropically while hydrogen atoms were included at
geometrically determined positions and ride on the carbon of
attachment. ADEP’s of (7) and (13) were generated using CAMERON
software.[35]
Atomic coordinates, bond lengths and angles, and displacement
parameters have been deposited with the Cambridge Crystallographic
Data Center (CCDC Nos 185848 and 185849 for compounds (7) and
(13), respectively).
ν
max (KBr) 2974, 1749, 1372, 1226, 1143, 1045, 1002, 732 cm–1. EI-
• +
MS m/z (70 eV) 347 [M – CH3CO•]+, (11%), 331 [M – CH3CO2 ] , (24),
242 (45), 200 (35), 157 (78), 115 (100), 98 (65).
Concentration of fraction B (RF 0.32 25:75 v/v ethyl acetate/hexane)
afforded compound (16) (40 mg, 12%) as a clear colourless oil, [α]D
+38.6 (c, 0.5) (Found: [M – CH3CO•]+, 347.0969. Calc for C16H22O11:
[M – CH3CO•]+, 347.0978). 1H NMR (CDCl3, 300 MHz) δ 6.12, s, 1H;
5.31, m, 2H; 5.18, m, 1H; 4.34, m, 1H; 4.27, dd, J 11.9 and 4.5 Hz, 1H;
4.14, dd, J 11.9 and 6.6 Hz, 1H; 2.12, s, 3H; 2.11(3), s, 3H; 2.10(9), s,
3H; 2.05, s, 6H. 13C NMR (CDCl3, 75 MHz) δ 170.4, 169.9, 169.5,
169.4, 168.8, 97.7, 79.3, 74.0, 70.0, 69.7, 62.5, 21.2, 21.0, 20.9, 20.7,
20.6. νmax (KBr) 1749, 1372, 1219, 1045, 967, 895, 602 cm–1. EI-MS
Acknowledgments
• +
m/z (70 eV) 347 [M – CH3CO•]+, (2%), 331 [M – CH3CO2 ] , (30), 245
We thank the Australian Research Council for the provision
of an APA(I) to X.M. and gratefully acknowledge the
assistance of Dr Gregg Whited (Genencor International Inc.,
Palo Alto, CA) in providing us with generous quantities of
compound (2) (X = Cl). Associate Professor J. Stevens
(University of New South Wales) is thanked for supplying an
authentic sample of D-talose and providing useful advice.
(100), 200 (35), 143 (92).
Method B. A magnetically stirred solution of a mixture of
compounds (13) and (14) (40 mg, 0.12 mmol, obtained by either one of
the two methods described immediately above) in THF/water (4 mL of
a 1 : 1 v/v mixture) was treated with trifluoroacetic acid (TFA) (0.4 mL).
The resulting mixture was stirred at 0–18°C for 20 h and then
concentrated under reduced pressure. The ensuing light-yellow oil was
dissolved in pyridine (4 mL), the resulting solution cooled to ca. 0°C
(ice-bath) and then treated with acetic anhydride (1 mL) and DMAP
(7 mg, 0.06 mmol). The reaction mixture was stirred at 0°C for 1 h and
then at 18°C for 23 h before being poured into a mixture of ethyl acetate
(10 mL) and ammonium chloride (15 mL of a saturated aqueous
References
[1] O. Hesse, J. Prakt. Chem. 1902, 66, 407.
[2] P. F. Wiley, M. V. Sigal, J. Am. Chem. Soc. 1958, 80, 1010.
[3] D. E. Wright, Tetrahedron 1979, 35, 1207, and references cited
therein.
[4] A. Markovitz, J. Biol. Chem. 1962, 237, 1767.
[5] R. J. Stack, Carbohydr. Res. 1989, 189, 281.
[6] (a) N. Shibuya, K. Amano, J. Azuma, T. Nishihara, Y. Kitamura,
T. Noguchi, T. Koga, J. Biol. Chem. 1991, 266, 16318; (b) M. B.
Perry, L. M. McLean, J. R. Brisson, M. E. Wilson, Eur. J.
Biochem. 1996, 242, 682; (c) N. Suzuki, Y. Nakaon, Y. Yoshida,
H. Nakao, Y. Yamashita, T. Koga, Biochim. Biophys. Acta 2000,
1517, 135.
[7] U. Zahringer, H. Rettenmaier, H. Moll, S. N. Senchenkova, Y. A.
Knirel, Carbohydr. Res. 1997, 300, 143.
[8] J. Weckesser, H. Mayer, I. Fromme, Biochem. J. 1973, 135, 293.
[9] J. B. Arena, E. C. Arnold, U.S. Pat. No. 4963382 A 19901016
(Chem. Abstr. 1991, 114, 100204).
[10] T. Mizuno, M. Yamamoto, M. Takeuchi, S. Shinkai, Tetrahedron
2000, 56, 6193.
[11] J. Zemek, V. Bilik, L. Zakutna, Folia Microbiol. 1975, 20, 467.
[12] V. Bilik, Czech Pat. No. 157429 19750415 (Chem. Abstr. 1975,
83, 164510).
solution). The separated organic phase was washed with NH Cl
4
(2 × 15 mL of a saturated aqueous solution) then dried (MgSO4),
filtered and concentrated under reduced pressure to give a light-yellow
oil. Subjection of this material to flash chromatography (silica gel,
gradient elution using 25 to 35% v/v ethyl acetate/hexane) afforded two
fractions, A and B.
Concentration of fraction
A (RF 0.26 in 4 : 2.5 : 5.5 v/v/v
ethyl acetate/dichloromethane/hexane) afforded a ca. 2 : 1 mixture of a
penta-O-acetyl-D-talofuranose and compound (15) (24 mg, 53%) as a
light-yellow oil which solidified on standing. Comparison of the 1H and
13C NMR data derived from this material with those obtained from
authentic samples of compound (15) provided a good match. The
following additional signals, attributed to the penta-O-acetyl-β-D-
talofuranose, were observed: 1H NMR (CDCl3, 300 MHz) δ 6.42, d, J
4.5 Hz, 1H; 5.30, m, partially obscured, 1H; 5.23, m, 1H; 5.15, m, 1H;
4.46, t, J 2.9 Hz, 1H; 4.31, dd, J 11.7 and 4.8 Hz, 1H; 4.16, m, 1H
[signals due to acetate methyl groups overlapping with those due to
equivalent groups in compound (15)]; 13C NMR (CDCl3, 75 MHz) δ
170.4, 169.9, 169.8, 169.7, 169.3, 93.9, 82.0, 77.4, 69.9, 69.8, 62.1,
29.9, 21.3, 21.1, 20.5 (one signal obscured or overlapping).
[13] (a) T. Komada, Bull. Chem. Soc. Jpn 1932, 7, 211; (b) G. J. F.
Chittenden, Carbohydr. Res. 1970, 15, 101.
[14] G. Hodosi, P. Kovac, J. Carbohydr. Chem. 1998, 17, 557.
[15] (a) R. S. Tipson, H. S. Isbell, Methods in Carbohydrate
Chemistry (Eds R. L. Whistler, M. L. Wolfram) 1962, Vol. 1,
p. 157 (Academic Press: New York NY); (b) V. Bilik, Czech Pat.
Concentration of fraction
B (RF 0.32 in 4 : 2.5 : 5.5 v/v/v
ethyl acetate/dichloromethane/hexane) afforded compound (16)
(10 mg, 22%) as a clear colourless oil. This material was identical, in
all respects, with the material prepared as described above from D-
talose.

A Chemoenzymatic Synthesis of Differentially Protected D-Talose Derivatives
103
No. 146465 19721215 (Chem. Abstr. 1973, 78, 148189); (c) V.
Bilik, Chem. Zvesti 1972, 26, 76 (Chem. Abstr. 1972, 77, 5718).
[16] H. Paulsen, F. Garrido Espinosa, W. P. Trautwein, Chem. Ber.
1968, 101, 186.
[27] (a) T. Hudlicky, J. A. Reed, in Advances in Asymmetric Synthesis
(Ed. A. Hassner) 1995, Vol. 1 p. 271 (JAI: Greenwich, CT);
(b) T. Hudlicky, D. A. Entwistle, K. K. Pitzer, A. J. Thorpe,
Chem. Rev. 1996, 96, 1195.
[17] D. Horton, J. S. Jewell, Carbohydr. Res. 1967, 5, 149.
[18] J. M. Harris, M. D. Keränen, H. Nguyen, V. G. Young, G. A.
O’Doherty, Carbohydr. Res. 2000, 328, 17.
[28] M. G. Banwell, N. Haddad, T. Hudlicky, T. C. Nugent, M. F.
MacKay, S. L. Richards, J. Chem. Soc., Perkin Trans. 1 1997,
1779.
[19] S, Y. Ko, A. W. M. Lee, S. Masamune, L. A. Reed III, K. B.
Sharpless, F. J. Walker, Tetrahedron 1990, 46, 245, and
references cited therein.
[20] (a) Y. Auberson, P. Vogel, Helv. Chim. Acta 1989, 72, 278; (b) J.
A. Marshall, K. W. Hinkle, J. Org. Chem. 1996, 61, 105; (c) K.
Kadota, K. Ogasawara, Tetrahedron Lett. 2001, 42, 8661.
[21] (a) G. Hodosi, P. Kovac, Carbohydr. Res. 1997, 303, 239; (b) O.
Kölln, H. Redlich, Synthesis 1996, 826.
[22] (a) J. S. Brimacombe, M. J. How, Chem. Ind. (London) 1962,
1382; (b) G. F. J. Chittenden, Carbohydr. Res. 1976, 52, 23.
[23] (a) M. B. Perry, A. C. Webb, Can. J. Chem. 1968, 46, 2481; (b)
M. B. Perry, V. Daoust, Can. J. Chem. 1973, 51, 974.
[24] M. G. Banwell, W. Ebenbeck, A. J. Edwards, J. Chem. Soc.,
Perkin Trans. 1 2001, 114.
[25] (a) M. G. Banwell, C. De Savi, K. Watson, Chem. Commun.
1998, 1189; (b) M. G. Banwell, C. De Savi, K. Watson, J. Chem.
Soc., Perkin Trans. 1 1998, 2251; (c) M. G. Banwell, S. Blakey,
G. Harfoot, R. Longmore, Aust. J. Chem. 1999, 52, 137; (d) M.
G. Banwell, C. De Savi, D. C. R. Hockless, S. Pallich, K. G.
Watson, Synlett 1999, 885; (e) M. G. Banwell, A. M. Bray, A. J.
Edwards, D. J. Wong, New J. Chem. 2001, 25, 3.
[29] (a) A. Chiocconi, C. Marino, R. M. de Lederkremer, Carbohydr.
Res. 2000, 323, 7, and references cited therein; (b) M. Bols, I.
Lundt, Acta Chem. Scand. 1990, 44, 252; (c) I. Dyong, L.
Baumeister, H. Bendlin, Chem. Ber. 1979, 112, 161; (d) J. Novak,
J. Smejkal, F. Sorm, Tetrahedron Lett. 1969, 1627.
[30] J. Kopf, P. Koell, Acta Crystallogr., Sect. B: Struct. Crystallogr.
Cryst. Chem. 1981, 37, 1127.
[31] Z. Otwinowski, W. Minor, Methods Enzymol. 1997 276,
307.
[32] P. Coppens, in Crystallographic Computing (Eds F. R. Ahmed, S.
R. Hall, C. P. Huber) 1970, pp. 255–270 (Munksgaard:
Copenhagen).
[33] A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi,
M. C. Burla, G. Polidori, M. Camalli, J. Appl. Cryst. 1994, 27,
435.
[34] (a) J. R. Carruthers, D. J. Watkin, Acta Crystallogr., Sect. A:
Cryst. Phys., Diffr., Theor. Gen. Cryst. 1979, 35, 698;
(b) D. J. Watkin, C. K. Prout, J. R. Carruthers, P. W. Betteridge,
CRYSTALS Issue 10 1996 (Chemical Crystallography
Laboratory: Oxford).
[35] D. J. Watkin, C. K. Prout, L. J. Pearce, CAMERON 1996
(Chemical Crystallography Laboratory: Oxford).
[26] T. Hudlicky, D. Gonzalez, D. T. Gibson, Aldrichimica Acta, 1999,
32, 35.