Structure-sweetness relationships for fructose analogs. Part I.

Synthesis and evaluation

of sweetness of 5-deoxy-D-threo-hexulose

Carbohydrate Research Institute and Department of Chetnistry, Queen's University, Kingston, Ont., Canada K7L 3N6
Received December 28, 1981
OLIVIERR. MARTIN,SIRKKA-LIISA KORPPI-TOMMOLA, and WALTERA. SZAREK. Can. J. Chem. 60, 1857 (1982).
5-Deoxy-D-threo-hexulose ("5-deoxyfructose", "5-deoxysorbose") has been prepared in six steps from D-fructose. The reac-
Can. J. Chem. Downloaded from www.nrcresearchpress.com by 97.122.199.51 on 02/06/18

tion of 2,3-0-isopropylidene-P-D-fructopyranosewith sulfuryl chloride afforded exclusively 5-chloro-5-deoxy-2,3-0-isopropyli-

dene-a-L-sorbopyranose in the key step. "5-Deoxyfructose" exists only in the *C,(D) pyranoid form in solution, and was
found to be much sweeter than L-sorbose and nearly as sweet as D-fructose. Comments on this unexpected sweetness
result are given.
OLIVIER R. MARTIN,SIRKKA-LIISA KORPPI-TOMMOLA et WALTERA . SZAREK.Can. J. Chem. 60, 1857 (1982).
Le dCsoxy-5-D-thrio-hexulose("dksoxy-5-fructose", "dksoxy-5-sorbose") a kt6 prepare en six Ctapes a partir du D-fructose.
La chloration de 1'0-isopropylidkne-2,3-P-D-fructopyrannosepar le chlorure de sulfuryle conduit exclusivement au chloro-5-
dCsoxy-5-0-isopropylidene-2,3-a-L-sorbopyrannose et constitue l'etape cle de la synthkse. Le "dCsoxy-5-fructose" adopte
uniquement la forme pyrannique *C,(D) en solution, et se revela beaucoup plus doux que le L-sorbose et presque aussi doux
que le D-fructose. L e resultat inattendu des tests de douceur est comrnente.

Introduction AH

D-Fructose, the well-known fruit sugar, is the

sweetest of the naturally occumng sugars;l how-
For personal use only.

ever, the structural features responsible for its high

sweetness have not yet been established with
accuracy. Since the sweetness diminishes with the I
appearance of the furanose forms during mutaro-
tation, the taste of D-fructose is thought to arise
only from the P-D-fructopyranose form (I), the
common form in the solid state. According to
Shallenberger's theory of sweet taste based on
intermolecular hydrogen bonding with the taste
I1
receptor of the tongue (2), the anomeric 2-OH and 111
the CH,OH groups should correspond, respective-
ly, to the H-donor, AH, and the H-acceptor, B, of
the principal saporous unit of D-fructose (1); the
stereochemical requirements between the AH and H0
HO
B groups are secured by the Lemieux effect (3).
Since the physico-chemical interaction leading to IV
sweet taste seems to need alipophilic function (4), a v
third, hydrophobic component (Y) has been added According to Birch ( 3 , hydrogen bonding be-
to the AH,B system to form a tripartite site (see I). tween HO-5 and the ing oxygen atom of P-D-
Studies on modified forms by Birch and co- fmctopyranose (V) would release the anomeric
workers (5) seem to confirm Shallenberger's intui- hydroxyl group to participate in the AH,B system,
tive proposal for the Sweetness of D-fmctose; thus, whereas the HO-2 group of the C-5 epimer (IV)
"2-deoxyfructose" (11, 2,6-anhydro-~-mannitol) would be inhibited by an intramolecular H-bond.
and P-~-arabinose(111) are indeed less sweet than ~ ~ r investigation
t h ~ ~ proved to be necessary to
D-fructose. However, L-sorbose, which adopts explain this sweetness difference and to obtain
almost exclusively the a - L - P Y ~form ~~O (IV)
S in
~ more information about the origin of the high sweet
solution (6), is far less sweet than D-fructose, taste of D-fructose.
although both of the ketoses are simply e~imericat Suppression of the 5-hydroxyl group of these
C-5. ketoses would constitute a very interesting mod-
'Sweetness comparisons are normally made on a weight ification to examine the role played by this func-
basis. tion. The corresponding 5-deoxyketose (5-
0008-4042/82/141857-06$01.OO/O
01982 National Research Council of CanadaIConseil national de recherches du Canada
 CAN. J. CHEM. VOL. 60, 1982
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deoxy-D-threo-hexulose) was obtained 35 years chlorosulfonyloxy group at C-5 by chloride ion is

ago as a by-product in the large scale biochemical
oxidation of sorbitol to L-sorbose (7). Our synthesis
involves six steps starting from D-fructose. The
reaction of 2,3-0-isopropylidene-P-D-fructop yra-
nose with sulfuryl chloride was anticipated (8) to
give mainly the 5-chloro-5-deoxy derivative and
constitutes the key step of the synthetic scheme.
For personal use only.
slow and the complete transformation of
2,3-0-isopropylidene-P-D-fructopyranose 1,4,5-
tri(chlorosu1fate) (A, Rf 0.67) (Scheme 2) into
5 - chloro - 5 - deoxy - 2,3 - 0 - isopropylidene - a - L -
sorbopyranose 1,4-di(chlorosu1fate) (B, Rf 0.76)
was achieved after 3 days at room temperature.
Dechlorosulfation of B with methanolic sodium

hydrogen carbonate gave 3 in 70% yield whereas

Results and discussion dechlorosulfation after only 2 hours at 20°C affor-
In contrast to the facile selective hydrolysis of ded mainly the cyclic sulfate 9 (58%) and some
1 ,2: 4 , 5 - di- 0 - isopropylidene- P - D-fructopyran- chlorodeoxy derivative 3 (9920) (Scheme 2). The
ose (9), partial hydrolysis of the 2,3:4,5-isomer 1 is regiospecificity of the reaction arises from the fact
known (10) to give a poor yield of 2,3-0-isopropyli- that nucleophilic attack by chloride ion at C-4 of A
dene-P-D-fructopyranose (2), the desired starting would be highly unfavorable because of dipolar
material (Scheme 1). Treatment of 1 with a strongly repulsion and steric interaction with the vicinal,
acidic ion-exchange resin in 95% ethanol gave, axial OR substituent at C-3 of A (8), which adopts
after interruption of the reaction at the optimal time mainly (see below) the 5 C , ( ~ conformation.
)
(tlc), 2 (1 I%), 1 (61%), and D-fructose. An overall Alkaline treatment of 3 gave readily 43-an-
yield of 27% of 2 could be obtained by repetition of hydro - 2 , 3 - 0 - isopropylidene - P - D - fructopyra-
the hydrolysis on the recovered 1 (four runs). nose (5) which was specifically reduced at the less
The reaction of 2 with sulfuryl chloride at low hindered site by lithium aluminum hydride to give
temperature afforded a two-component mixture (R, the 2,3-acetonated form of "5-deoxyfructose" (6)
0.67 and 0.76, solvent B). Displacement of the in 94% yield. Deacetalation of 6 with H+-resin in
 MARTIN E T AL.

1 . Vicinal coupling constants for 4-9 (Hz)"

TABLE

Compound J3.4 J4,5A J4.5~ J5~.6h J ~ ~ \ . 6 ~ J ~ ~ , 6 ~' ~ D . 6 8

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"A,B assignments made on basis of chemical shifts (6,< 6,); for 6 and 7: H-5A= H-S,,,,,, H-5B= H-S,,,.,,,,,,,; H-6A=
H-6,,,uat,,r,,,, H-6B = H-6".,,,,.

aqueous ethanol gave "5-deoxyfructose" (7) in 6 (1.14) is an indication of a considerable flattening

78% yield together with some ethyl glycoside of 7 of the pyranoid ring.
(6%) which was characterized as its acetylated The presence of the epoxide ring in 5 changes
derivative 8. dramatically the conformation of the sugar ring
Owing to the lack of a 5-OH group, 7 cannot exist which adopts an OH2- or 2Ho-type conformation
in a furanose form and its constitutional equilibri- (13). Furthermore, the cyclic sulfate 9 appears to
um is much simpler than in the case of D-fructose. exist in the same non-chair conformation as do
As in the case of L-sorbose, 7 does not show any 2,3 :4,5 - di - 0 - isopropylidene - P - D - fructopyra-
mutarotation and was found on the basis of its nmr nose (1 1) and di-0-isopropylidene-D-arabinose or
parameters to adopt exclusively the 2 C , ( ~ )P-D- di-0-isopropylidene-D-galactose derivatives (14),
pyranoid form (7a) in solution. If the ethyl glycos- namely close to the 6S4 skew conformation (see
For personal use only.

ide 8 has the same conformation, then the 2,3-0- 9a).

acetonated precursors exhibit completely different
types of conformations, as shown by the vicinal J Sweefness of "5-deoxyfructose"
values (see Table 1). Thus, the small J , , coupling The sweetness of a 3% solution of 7 has been
constants observed for the chlorodeoxy derivative evaluated by four trained panelists and compared
4 and the protected "5-deoxyfructose" indicate in several sessions to the tastes of 3% solutions of
that these compounds adopt the unusual ,C2 con- D-fructose and L-sorbose, and of water. All of the
formation (see 3a and 6a); however, according to individual results showed clearly that "5-deoxy-
the other coupling-constant values, the true con- fructose" (7) is much sweeter than L-sorbose and
formation probably deviates from the ideal chair to nearly as sweet a s ~ f r u c t o s e .In fact, the sweet-
a flattened chair, as in the case of 2,3-0-isopropyli- ness of D-fructose and of its 5-deoxy analog are
dene-P-D-fructopyranose (1 I). very difficult to differentiate as two panelists found
Interestingly, the Lambert R-value (12), which the latter sweeter than the common ketose. How-
accounts for the chair distortion of (hetero)cyclo- ever, owing to the presence of other, non-sweet
hexanes, can be calculated for the ethylene frag- forms in D-fructose solutions, P-D-fructopyranose
can still be considered as being slightly sweeter
than the corresponding 5-deoxy-ketopyranose.
According to the existing theory ( 3 , 5-deoxy-
fructose was expected to exhibit a sweetness close
to that of L-sorbose. Our results show now that the
axial, 5-hydroxyl group is not an indispensable
component of the saporous unit of D-fructose and
that the proposed mechanism of a "proton-
releasing" effect on the HO-2 group by a competi-
tive hydrogen bonding of HO-5 with the ring
oxygen is not tenable. The large difference in

ments of 6 and 7. As expected, 7 exhibits an

R-value (1.93) close to that of the R-parameter of
D- Fructose
an undistorted chair (2.16), whereas the R-value for -L - Sorbose
- -
 1860 CAN. S. CHEM. VOL. 60, 1982
sweetness between the two ketoses epimeric at C-5
cannot arise only from a different degree of hydro-
gen bonding between HO-2 and the ring oxygen. It
now appears that the equatorial 5-OH group exerts
some detrimental influence on the saporous unit,
possibly of a steric nature, which could preclude a
correct alignment of the sugar on the taste receptor.
Further work is currently in progress to prepare
new model compounds to gain more information
about the intriguing problem of the sweetness of
Can. J. Chem. Downloaded from www.nrcresearchpress.com by 97.122.199.51 on 02/06/18
D-fructose.
Experimental
Melting points were determined on a Fisher-Johns apparatus
and are uncorrected. Optical rotations were measured with a
Perkin-Elmer model 141 automatic polarimeter at 23 f 3°C.
Infrared spectra were recorded with a Perkin-Elmer 598
spectrophotometer. The 'Hmr spectra were recorded with a
Bruker HX-60 (60 MHz) or a Bruker CXP-200 (200 MHz)
spectrometer in chloroform-d with tetramethylsilane (TMS) as
the internal standard, unless otherwise stated. The "Cmr
spectrum was obtained at 15.09MHz on a Bruker HX-60
spectrometer equipped with an FT60M Fourier transform
accessory; chemical shifts are given in parts per million down-
For personal use only.
field from TMS. Some of the coupling constants are given in
Table 1. Thin-layer chromatography (tlc) was performed using
silica gel G as the adsorbent in the following solvent systems
(vlv): (A) ethyl acetate; (B) toluene - ethyl acetate, 2:l; (C)
toluene - ethyl acetate, I: 1; (D) ethyl acetate - toluene, 3: 1; (E)
ethyl acetate - methanol-water, 7: 1:0.2. The developed plates
were dried and compounds located by spraying with 10%
aqueous sulfuric acid containing 1% cerium sulfate and 1.5%
molybdic acid, and heating at 150°C. Column chromatography
was performed on silica gel 60 (70-230 mesh, Merck). The term
"petroleum ether" refers to the fraction of bp 30-60°C.
(I)
2,3;4,5-Di-O-isopropylidet1e-P-~-fructopyrr111ose
This compound was prepared from D-fructose (72g, 0.4mol)
by the method of Brady (15). The crude product (91.2g, 87.7%)
was recrystallized from ether-pentane to afford white needles
(57g, 55%), mp 97°C (lit. (15) mp 97"C), [aIDZ3-24.2" (c 0.6,
CHCI,) (lit. (15) [aIDz5-24.7" (c 1.1, CHCI,)). The 'Hmr
spectrum is in agreement with the published spectrum (1 1).
2,3-0-Isopropylidene-P-D-fr~ictopyranose (2)
This compound was prepared by a modification of the
procedure of Wolfrom et al. (10). Compound 1 (45 g, 0.17 mol)
was treated with Dowex 50W-X8 (Hf) resin (20g) in 95%
ethanol (160mL) at room temperature. Thin-layer chromato-
graphic analysis (solvent A) showed a slow formation of 2 (R,
0.40) together with fructose (R, 0, main product); after -6
days the proportion of 2 was the greater. The resin was removed
by filtration and the solvent evaporated. The residue was taken
up in water and the resulting mixture extracted with methylene
chloride (2 x 70mL, 1 x 5OmL); the combined extracts were
washed with water (3 x 25 mL), dried (MgSO,), and concentra-
ted to afford pure 1 (27.6g, 61%).
The combined aqueous phases were concentrated to a
yellowish syrup, which was chromatographed on a silica gel
column using solvent A as eluent to give pure 2 as a syrup (4.1 g,
11%). The hydrolysis was repeated on the recovered 1 to yield
finally 10.2g (27%) of 2 from 45g of 1 in four runs. The
separation of 2 from D-fructose could also be achieved by
continuous extraction of the aqueous solution with chloroform
for three days, drying the organic phase (MgSO,), evaporating
the solvent, and treating the crude 2 with Darco, activated
decolorizing charcoal in water. Compound 2 exhibited [aIDZ3
+13.0° (c 1.5, water) (lit. (10) [a], +17.5" (c 2.3, water) after
purification through the crystalline triacetate). The 'Hmr spec-
trum of 1,4,5-tri-0-acetyl-2,3-0-isopropylidene P-o-fructopy-
ranose, prepared according to the procedure of Wolfrom et 01.
(lo), was in agreement with the published spectrum (11).
5-Cl1loro-5-deoxy-2,3-O-isopropylidene-a-~-
sorbopyranose (3)
This compound was prepared by a modification of the general
procedure (16) for reactions with sulfuryl chloride. A solution of
2 (5.3g, 24.1 mmol) in dry chloroform (100mL) and pyridine
(1 1.7 mL, 145 mmol, 2 equiv/OH) was cooled at -7PC (Dry Ice
- acetone). Sulfuryl chloride (9.75 mL, 120.5mmol) was added
-
dropwise (1 h) to the viscous reaction mixture with vigorous
stirring. The mixture was stirred at -65°C for a further 5 h,
then allowed to warm slowly to room temperature; stining was
continued at 20°C for 72 h after which time tlc revealed that all of
the 2,3-0-isopropylidene-P-D-fructopyranose1,4,5-tri(chloro-
sulfate) (R, 0.67, solvent B) had been converted into 5-
chloro-5-deoxy-2,3-0-isopropylidene-a-~-sorbopyranose 1,4-
di(ch1orosulfate) (R, 0.76). The reaction mixture was poured
into ice-water (150 mL) and the chloroform layer separated.
The aqueous phase was extracted with chloroform (3 x 50mL);
the combined organic phases were washed with saturated
aqueous sodium hydrogen carbonate (SOmL), then with water
(50mL), dried (MgSO,), and concentrated. The residue was
treated with sodium hydrogen carbonate (13 g) in methanol
(150 mL) for 12h a t room temperature to achieve dechlorosulfa-
tion. The mixture was filtered and the filtrate was evaporated;
the residue was dissolved in chloroform (100mL) and water
(IOmL). The aqueous layer was extracted with chloroform
(3 x IOmL) and the combined organic phases were dried
(MgSO,) and concentrated. The crude product was combined
before purification with the product obtained from the same
reaction using 2.1 g (9.6mmol) of 2; column chromatography
(solvent C) afforded 38 mg (< 1%) of the cyclic sulfate derivative
9 and 5.59g (69.7%) of 3 which was recrystallized from
chloroform-ether - petroleum ether to give white crystals, mp
88-90°C; R, 0.14 (solvent B); [aIDZ3 +24.0° (c 0.8, CHCl,); v,,,
(KBr): 3360, 3480 (OH) and 1373, 1384cm-I (CMe,); IHmr 6:
1.40 and 1.64 (2s, 2 x 3H, CMe,), 3.34 (t, lH, Jl,,oH= 6.5Hz,
= 5.7H2, exchanged in D,O, HO-I), 3.61 (dd, dafter D,O
exchange, lH, J l h , l B11.5H2,
= H-1A). 3.85 (dd, d after D,O
exchange, l H , H-IB), 3.92-4.16 (m, 3H, H-6A, H-6B, H-3 or
H-5), 4.24-4.37 (m, 3H, 2H after D,O exchange, H-4, HO-4, H-5
or H-3). Anal. calcd. for CgH,,C105: C 45.35, H 6.33, CI 14.85;
found: C 45.35, H 6.42, C1 14.42.
1,4-Di-O-acetyl-S-chloro-5-deoxy-2,3-O-isopropylide11e-
a-L-sorbopyranose (4)
Acetylation of 3 (200mg, 0.84mmol) by the standard proce-
dure afforded 250mg (92%) of homogeneous 4 which was
recrystallized from ether - petroleum ether, mp 47-4YC, Rr
0.58 (solvent B), [aIDZ3 +27.5" (c 1.16, CHCI,); v,,, (KBr): 1745
(C=O), 1382 and 1390cm-I (CMe,); 'Hmr 6: 1.43 and 1.67
(2s, 2 x 3H, CMe,), 2.15 and 2.16(2s, 2 x 3H, 2OAc), 3.98-4.10
(m, 3H, H-5, H-6's). 4.17 (d, IH, J,, = 2.9Hz, H-3), 4.21 (d,
l H , J l h , l B12.2Hz,
= H-IA), 4.32 (d, l H , H-IB), 5.48 (narrow
m, lH, H-4). Anal. calcd. for Cl,HlgC1O,: C 48.38, H 5.93, C1
10.99; found: C 48.54, H 6.14, CI 11.09.
4,s-cyclic suljiate (9)
2,3-0-Isopropylidene-P-D-fructopyranose
A solution of compound 2 (2.0g, 9.lmmol) in chloroform
 MARTIN E T AL. 1861

(60 mL) containing pyridine (4.4mL, 55 mmol) was treated with
sulfuryl chloride (3.7 mL, 45.6 mmol) at low temperature as
described for the preparation of 3, and the reaction was stopped
after having been stirred for 2 h at room temperature. The
reaction mixture was treated with sodium hydrogen carbonate
in methanol for 70 h and processed; column chromatography
afforded 1.5g(58%) of syrupy 9and 0.19g(9%) of 3. Compound
9 crystallized from ether - petroleum ether, mp 82.5-84°C R,
0.46 (solvent B), [aIDz3-23.8' (c 2.1, CHCI,); v,,, (KBr): 3370
(OH), 1400 and 1 2 0 5 ~ m -(SO,);
~ IHmr 6: 1.46 and 1.60 (2s,
2 x 3H, CMe,), 2.16 (t, lH, JIsoH = 7 Hz, exchanged in D,O,
HO-I), 3.77 (d, s after D,O exchange, 2H, H-l's), 4.05 (dd, lH,
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5-Deoxy-P-D-threo-hexulopyranose(7) ("5-deoxy-D-fnrclose"
or "5-deoxy-L-sorbose")
Compound 6 (2.7g, 13.2mmol) was treated with Dowex
50W-X8 (H+) resin (75 g) in an ethanol (200 mL) - water (50 mL)
mixture at room temperature for 7 days. The resin was removed
by filtration and the filtrate concentrated. Resolution of the
reaction mixture by column chromatography (solvent E) afford-
ed 140 mg (5%) of 6, 150 mg (6%) of the ethyl glycoside of 7 (R,
0.42), 200mg of a mixture of the latter and 7, and 1.69g(78%) of
homogeneous (tlc) 7, which was recrystallized from methanol -
acetate; mp 117.5-1 18.5"C, (lit. (7) mp 110°C); R, 0.23 (solvent
E), [aIDz3-65.8" (c 1.1, H,O) (lit. (7) [a], -67.0" (c 1.0, H,O){;

J,,,,= 0.9Hz, J6,,,,= 14.7Hz, H-6A),4.15 (dd, lH, J,,,,= 1.7 v,, (KBr): 3350 (very broad, OH), 1050, 1095, and 1150cm- ;
HZ, H-6B), 4.58 (d, lH, J3,,= 2.4Hz, H-3), 5.04 (ddd, lH, 'Hmr (CD,OD; a = axial,, e = equatorial) 6: 1.62 (tdd, lH,
J,,, = 7.8 Hz, H-5), 5.33 (dd, lH, H-4). Anal. calcd. for C9HI4- J,,,,, = 12.8Hz, J,,,,, = 12.8H2, J,,,, = 11.4Hz, J,,,,, = 5.2
SO,: C 38.29. H 5.00; found: C 38.04, H 5.07. Hz, H-5a), 1.89 (dddd, lH, J,,,, = 5.1 Hz, J,,,,, = 2.2Hz,
J,,,,,= 1.5Hz, H-5e), 3.39 (d, lH, J , , = 9.5Hz, H-3), 3.45 (d,
4,5-At1hydro-2,3-0-isopropylidene-~-~-fr~rc1opyr~111ose (5) lH, J,,,,,= 11.1Hz, H-IA), 3.63 (ddd, lH, J,,.,,= 11.5Hz,
Compound 3 (4.95 g, 20.7 mmol) was treated with potassium H-6e), 3.66 (d, lH, H-IB), 3.87 (ddd, lH, H-4), 3.95 (ddd, lH,
hydroxide (l.4g, 25 mmol) in ethanol (120 mL) at room tempera- H-6a); (D,O) 6: 1.71 (-qd, l H , J,,,,,= 12Hz, J,,,,,= 12Hz,
ture for 6h. The mixture was neutralized with 1N hydrochloric J4,,,= 12Hz, JSa,,"= 5.5Hz, H-5a), 2.05 (dm, l H , J,,,,= 5Hz,
acid and concentrated. The residue was dissolved in methylene J,,,,,= 2Hz, J5,.,,=2Hz, H-Se), 3.51 (d, lH, J3,,=9.5Hz,
chloride (100mL) and water (1OmL) the separated aqueous H-3), 3.54(d, lH, JIA,,,= 11.7H2, H-lA), 3.79(d, lH, H-lB),
layer washed with methylene chloride (3 x 5mL) and the 3.72-4.05 (m, 3H, H-4, H-6a, H-6e); I3Cmr (D,O) 6: 33.9 (C-5),
combined organic phases dried over magnesium sulfate. Con- 59.8 (C-6), 64.8 (C-1), 69.4, 73.3 (C-3, C-4), 99.3 (C-2). Anal.
centration of the solution afforded 4.1 g (98%) of crystalline 5. calcd. for C,H,,O,: C 43.90, H 7.37; found: C 43.50, H 7.00.
An analytical sample was obtained from ether - petroleum
ether, mp 114-1 16.5"C, R,0. 12 (solvent B); [aIDz3- 11. lo(c 0.8, E1hyl1,3,4-tri-O-acetyl-5-deoxy-~-~-threo-hexulopyrat1oside
For personal use only.

CHCl,); v,, (KBr): 3460 (OH), 1377 and 1387cm-I (CMe,); (8)
IHmr 6: 1.45 and 1.55 (2s, 2 x 3H, CMe,), 2.37 (broad s , lH, The syrupy ethyl glycoside of 7 (150mg) obtained as de-
exchanged in DzO, HO- l), 3.28 (broad d, lH, J,., = 4.1 Hz, scribed above was acetylated by the standard procedure to
J,,,, = 1.1 Hz, J,,,,< 0.5 Hz, H-5), 3.39 (dd, lH, J,,, = 0.9 Hz, afford 220mg (89%) of 8. An analytical sample of syrupy 8 was
,
H-4), 3.50 (broad dd, d after D,O exchange, lH, J ,,,, = 11.7 obtained by column chromatography (hexane - ethyl acetate,
HZ, J l , . o H - 7 H ~ , H-IA), 3.64 (d, lH, H-IB), 4.10 (d, lH, 2: 1(vlv)), Rr0.43 (solvent B); [aIDz3-75.6" (c 1.11, CHCl,); v,,,
H-6A), 4.21 (d, lH, H-6B), 4.41 (s, lH, H-3). Anal. calcd. for (film): 1750cm-I (C=O); 'Hrnr (CD,OD; a = axial, e = equa-
C9H1,05:C 53.46, H 6.98: found: C 53.77, H 7.15. torial) 6: 1.26 (t, 3H, OCH,CH,), 1.84 (m, lH, J,,,, = lOHz,

5-Deoxy-2,3-0-isopropylidene-~~-threo-hexu/opyranose (6)
J5,.,,=13Hz, J,,,,-8Hz, J,,.,,-llHz,
-
H-5a), 2.03, 2.09,
and 2.12 (3s, 3 x 3H, 3 OAc), 2.18 (m, lH, J,.,, = 5 Hz, J,,,,, 2
A solution of 5 (4.0g, 19.8mmol) in dry tetrahydrofuran Hz, J,,.,,- 2 Hz, H-5e), 3.51 (qd, lH, JHAScH, = 6.8 Hz,
(40mL) was added, dropwise over a period of 45 min, under = 9.2 HZ, 0CHAHBCH3),3.67 (qd, l H , JHDsCH, = 7.2 HZ,
nitrogen to a suspension of lithium aluminum hydride (2.3 g, 0CHAHBCH3),3.8 (m, 2H, H-6a, H-6e), 4.04 (d, lH, J = 11.7
61 mmol) in tetrahydrofuran (80mL) at room temperature. HZ, H-IA), 4.29 (d, lH, H-IB), 5.19(d, lH, J 3 , =lOHz, H-3),
Stirring was continued for 3.5h at 20°C and 2h at reflux 5.28 (td, lH, H-4). Anal. calcd. for C14H220S: C 52.83, H 6.97;
temperature. Ice-water (20mL) was then added carefully; the found: C 52.78; H 7.35.
mixture was filtered, the filtrate neutralized with 0.5 N hydro-
chloric acid and concentrated. The residue was dissolved in Acknowledgements
chloroform (50mL) and water (5 mL), the separated aqueous The authors are grateful to the Natural Sciences
layer concentrated, and the crystalline residue triturated with and Engineering Research Council of Canada for
chloroform (5 mL) and then with acetone (5 mL). The combined
organic phases were dried (MgSO,) and concentrated to afford its support of this work in the form of a grant (to
3.8g (94%) of homogeneous (tlc) 6. Pure 6 (3.1 g, 77%) was W.A.S.), to the Fonds National Suisse de la
obtained by crystallization from chloroform-ether - petroleum Recherche Scientifique for its award of a fellowship
ether followed by column chromatography (solvent D) and (to O.R.M.), and to Queen's University for finan-
crystallization as before; mp 95-97"C, Rr0.22(solvent D), [a],,,
+28.6" (c 1.0, CHCl,); v,, (KBr): 3410 (OH), 1375 and 1384 cial assistance (to S.-L. K.-T.).
cm-I (CMe,); 'Hmr 6: 1.40 and 1.58 (2s, 2 x 3H, CMe,), 1.72
(tdd, lH,J,,,, = 2.6Hz, J,,,,,= 14.3Hz, J,,,,, = 5.6Hz, J,,.,, 1. R. S. SHALLENBERGER. Pure Appl. Chem. 50, 1409 (1978);
= 5.6H2, H-5A), 2.12 (tdd, lH, J4,,,= 5.6H2, JSBs6*= 5.6H~, Zuckerindustrie, 104, 121 (1979).
J5B,6B = 7.2Hz, H-5B), 3.47 (dd, IH, JIA,OH = 5.OHz, JIB,oH 2. R. S. SHALLENBERGER. J. Food Sci. 28,584 (1963); New
= 7.5Hz, exchanged in D,O, HO-l), 3.67 (dd, d after D,O ex- Sci. 407, 569 (1964); R. S. SHALLENBERGER and T. E.
change, lH, J,,,,,= 11.5Hz, H-IA), 3.77 (d, lH, J4,0H=6.0 ACREE.Nature, 216, 480 (1967); J. Agric. Food Chem. 17,
Hz, exchanged in D,O, HO-4), 3.87 (obscured td, lH, J,,,,,= 701 (1969).
11.9 Hz, H-6A), 3.88 (dd, d after D,O exchange, lH, H-lB), 3.97 3. R. U. LEMIEUXand J. T. BREWER.ACS Adv. Chem.
(ddd, lH, H-6B), 4.12 (d, lH, J,,, = 2.7 HZ, H-3), 4.30 (tt, td Series, 117, 121 (1973).
after DzO exchange, lH, H-4). Anal. calcd. for C,H,,O,: 4. L. B. KIER.J. Pharm. Sci. 61, 1394 (1972).
C 52.93, H 7.90; found: C 52.88, H 8.10. 5. M. G. LINDLEY and G. G. BIRCH.J. Sci. Food Agr. 26,
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