Kiliani reactions on ketoses: Branched carbohydrate building blocks from D-tagatose and D-psicose

Article abstract of DOI:10.1016/j.tetlet.2005.06.030

D-Tagatose and D-psicose on treatment with sodium cyanide gave mixtures of branched sugar lactones; extraction of the crude products by acetone in the presence of acid permits direct access to branched carbohydrate diacetonides, likely to be of value as new chirons. In both cases, the major lactone products-diacetonides with a 2,3-cis-diol relationship-can be crystallised in around 40-50% yield from the ketohexose. A practical procedure for the conversion of 30 g of D-tagatose to give 24 g of 2,3:5,6-di-O-isopropylidene-2- C-hydroxymethyl-D-talono-1,4-lactone is reported.

Full text of DOI:10.1016/j.tetlet.2005.06.030

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 5755–5759
Kiliani reactions on ketoses: branched carbohydrate building
blocks from D-tagatose and D-psicose
Raquel Soengas,a Ken Izumori,b Michela Iezzi Simone,a David J. Watkin,a Ulla P. Skytte,c
Wim Soetaertd and George W. J. Fleeta,*
aChemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK
bRare Sugar Research Center, Kagawa University, Mikicho, Kagawa 761-0795 Japan
cArla Foods Ingredients, Viby J, DK-8260 Denmark
dDepartment of Biochemical and Microbial Technology, Ghent University, 9000 Gent, Belgium
Received 17 March 2005; revised 3 May 2005; accepted 6 June 2005
Abstract—D-Tagatose and D-psicose on treatment with sodium cyanide gave mixtures of branched sugar lactones; extraction of the
crude products by acetone in the presence of acid permits direct access to branched carbohydrate diacetonides, likely to be of value
as new chirons. In both cases, the major lactone products—diacetonides with a 2,3-cis-diol relationship—can be crystallised in
around 40–50% yield from the ketohexose. A practical procedure for the conversion of 30 g of D-tagatose to give 24 g of 2,3:5,6-
di-O-isopropylidene-2-C-hydroxymethyl-D-talono-1,4-lactone is reported.
ꢀ 2005 Elsevier Ltd. All rights reserved.
1. Introduction
merisations with microbial oxidation–reduction proce-
dures. A key step is the use of D-tagatose 3-epimerase
for the equilibration of ketohexoses, allowing the prepa-
ration of D-psicose 5 from D-fructose.11
Almost all readily available carbohydrate scaffolds con-
tain linear carbon chains.1 Although the Kiliani ascen-
sion2 on unprotected ketoses3,4 (to provide branched
sugar building blocks) has been little investigated,5,6
the convenient preparations of branched carbon chain
diacetonides from D-fructose and L-sorbose7 suggest
that a new family of carbohydrate chirons containing
branched carbon chains would be readily available from
the chiral pool. D-Fructose and L-sorbose are no longer
the only accessible ketohexoses.
This letter reports the Kiliani reactions of D-tagatose 1
and D-psicose 5 with sodium cyanide, followed by aceto-
nation, to give readily crystallised diacetonides 2 and 6,
respectively, as accessible branched chirons derived from
sugars (Scheme 1); other acetonides formed in smaller
amounts were also identified. From a practical point
of view, the small amount of the spiro-cis-diacetonide
3 from tagatose—and the absence of any spiro-cis-
diacetonide 7 from psicose—make these experimental
procedures easier than the corresponding Kiliani reac-
tions on fructose and sorbose.
Recent developments in biotechnology have shown that
any monosaccharide can be made available cheaply in
substantial quantity by environmental friendly green pro-
cesses. An outstanding example of a sugar that has chan-
ged its status in a few years from rare ($5000 per lb) to
common ($2.5 per lb) is D-tagatose 1, a healthy sweetener
prepared cheaply from galactose8 and used in soft drinks
and ready-to-eat cereals.9 Izumoring10 provides a concep-
tual advance in the availability of monosaccharides, dem-
onstrating that all aldoses and ketoses might be available
in substantial quantities by a combination of enzymic epi-
2. Branched chirons from D-tagatose
The Kiliani reaction of cyanide with D-tagatose 1 gave a
mixture of the two lactones 9 and 10 in a ratio of
approximately 3:1. Extraction of this crude product with
acetone in the presence of acid allowed the small amount
of the diacetonide from the spiro-cis-diol 3 to be sepa-
rated from the other products. Most of cis-diol fused
diacetonide 2, the major product, can then be isolated
*
Corresponding author. E-mail: george.fleet@chem.ox.ac.uk
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.06.030

5756
R. Soengas et al. / Tetrahedron Letters 46 (2005) 5755–5759
O
O
O
O
O
O
O
O
O
OH OH
O
O
O
O
O
CH2OH
CH2OH
HOH2C
O
O
HO O
HO
OH
O
O
44% directly crystallised
51% isolated
1 D-Tagatose
3% isolated yield
11% isolated yield
2
3
4
O
O
O
O
O
O
O
O
O
O
O
OH OH
O
CH2OH
CH2OH
O
HOH2C
O
O
HO O
O
HO
OH
O
O
5 D-Psicose
38% directly crystallised
19% isolated yield
NONE isolated
6
7
8
Scheme 1. Products from Kiliani ascension–acetonation of tagatose and psicose.
(iii)
OH
O
O
O
(iii)
O
O
O
O
O
HOH2C
O
+
O
O
CH2OH
CH2OH
HO
OH
HO
O
O
O
9
3
2
OH OH
(ii)
(i)
CH2OH
+
HOH2C
+
OH
O
(iv)
(v)
1 D-Tagatose
OH
O
O
O
O
O
(iii)
O
O
HOH2C
O
OH
CH2OH
O
O
O
CH2OSiMe2tert-Bu
HO
O
O
HO
O
10
4
11
Scheme 2. Reagents and conditions: (i) NaCN, H2O; then H+/H2O; (ii) Me2CO, H2SO4, CuSO4; (iii) CF3CO2H, H2O; (iv) tert-BuMe2SiCl,
imidazole, DMF; (v) n-Bu4NF, THF.
by crystallisation. Removal of the remaining 2 as its pri-
mary tert-butyldimethylsilyl (TBDMS) ether from the
mixture of diacetonides allows the isolation of moderate
amounts of the pure trans-spiro-diacetonide 4 with the
more hindered secondary alcohol free. The following
provides a practical procedure for the Kiliani reaction
of tagatose on a moderate scale (Scheme 2).
red at room temperature for 6 h when TLC (ethyl ace-
tate/cyclohexane 1:1) indicated the formation of a
major product (Rf 0.29) and a minor one (Rf 0.32).
The mixture was then neutralised with solid sodium car-
bonate, filtered and the solvent evaporated. The residue
was shaken with dichloromethane (300 mL) and water
(300 mL); the aqueous layer was further extracted with
dichloromethane (2 · 100 mL). The combined organic
extracts were dried (magnesium sulfate), filtered and
evaporated to produce a mixture of diacetonides, which
was separated by flash chromatography (ethyl acetate/
cyclohexane 2:3!1:1), to yield the cis-diol spiro-diaceto-
nide 312 (1.52 g, 3%) and a 5:2 mixture (1H NMR;
integration of H-3 in 2 and H-2 in 4) of the cis-fused
diacetonide 2 and the trans-diol spiro-diacetonide 4
(31.31 g) (combined yield of diacetonides (32.8 g) is
68% from tagatose). The cis-fused diacetonide 213
(21.01 g, 44%) was directly crystallised from the mixture
A solution of D-tagatose 1 (30.00 g, 0.17 mol) and
sodium cyanide (10.62 g, 0.22 mol) in water (300 mL)
was stirred at room temperature for 24 h and then
refluxed until evolution of ammonia had ceased (approx
12 h). The reaction mixture was allowed to cool to room
temperature and passed through a column of Amberlite
IR-120 H+. The solvent was removed and the resulting
residue of lactones 9 and 10 (33.63 g) treated with ace-
tone (450 mL), concentrated sulfuric acid (9 mL) and
copper sulfate (10.00 g). The reaction mixture was stir-

R. Soengas et al. / Tetrahedron Letters 46 (2005) 5755–5759
5757
OH
TBDMSO
O
O
OH
O
O
O
O
(iii)
(iv)
O
HOH2C
CH2OTBDMS
O
CH2OH
O
O
CH2OH
OH
14
O
O
HO
6
12
OH OH
OH
(ii)
(i)
+
CH2OH
+
TBDMSO
O
HOH2C
O
OH
O
CH2OTBDMS
O
O
5 D-Psicose
15
OH
O
O
O
(iii)
HOH2C
O
O
OH
CH2OH
O
O
OH OH
HO
HO
CH2OH
O
HOH2C
OH
16 L-Psicose
O
13
8
Scheme 3. Reagents and conditions: (i) NaCN, H2O; then H+/H2O; (ii) Me2CO, H2SO4, CuSO4; (iii) CF3CO2H, H2O; (iv) CH3CO2H, H2O; then tert-
BuMe2SiCl, imidazole, DMF.
from ether/hexane. Evaporation of the mother liquors
afforded a 1:3 mixture of 2 and trans-diol spiro-diaceto-
nide 4 (10.06 g). The structure of the spiro-314 and cis-
fused 215 diacetonides were firmly established by X-ray
crystallographic analysis.
gave a crude product mixture of the lactones 12 and
13. Extraction of the crude mixture of lactones with ace-
tone in the presence of copper sulfate and sulfuric acid
gave a mixture of only two diacetonides 6 and 8 in an
approximate ratio of 2:1 (56% and 28% yield, respec-
tively) in a combined yield of 84%. There was no evi-
dence of the formation of the spiro-cis-diacetonide 7.
The major product 620 could be directly crystallised
from the crude extract (ether/hexane) in 38% yield, leav-
ing a residue in which the ratio of 6–8 was 1:3. There
was no need for any chromatography in the isolation
of 6 by this procedure.
Pure trans-diacetonide 4 (which contains a hindered sec-
ondary alcohol) may be isolated from the mixture by re-
moval of 2 (which contains a primary alcohol) as its tert-
butyldimethylsilyl (TBDMS) ether 11. Thus, TBDMS
chloride (6.65 g, 44.10 mmol) was added to the mixture
of 2 and 4 (10.06 g, 35.62 mmol) in the presence of imid-
azole (6.00 g, 85.00 mmol) in dry DMF (100 mL) at
À20 ꢁC, and the resulting reaction mixture was stirred
at this temperature for 4 h. The solvent was then evapo-
rated and the residue was shaken with chloroform
(200 mL) and water (3 · 150 mL); the organic layer
was dried (magnesium sulfate) and the solvent removed
to give a residue, which was separated by flash chroma-
tography (ethyl acetate/cyclohexane 1:4!1:1), to give
the primary silyl ether 1116 (4.93 g) as a colourless oil
and the trans-spiro compound 417 (5.39 g, 11% based
on tagatose) as a white solid. Removal of the TBDMS
ether from 11 by tetra-n-butylammonium fluoride in
THF gave a further quantity of the cis-fused acetonide
2 (3.25 g, 7.0% from tagatose). Thus the final isolated
yields of the acetonides 3, 2 and 4 from D-tagatose 1
were 3%, 51% and 11%, respectively.
A pure sample of the spiro-trans-diacetonide 821 (19%
yield) could be isolated by removal of 6 as its TBDMS
ether; however, the selectivity between the alcohols 6
and 8 in the silylation reaction makes this an inefficient
isolation procedure. Further studies on a practical pro-
cedure for the isolation of the acetonides 6 and 8 on a
larger scale are in progress.
The structure of 6 was firmly established by removal of
the side chain acetonide with aqueous acetic acid fol-
lowed by silylation of both primary alcohols by TBDMS
chloride in DMF in the presence of imidazole to give the
bis-TBDMS ether 14 (71% overall yield). The silyl ether
21
1
14, ½aŠ À13.2 (c 1.1, CHCl3) had identical 13C and H
D
NMR and infrared spectra to those of its enantiomer
15, ½aŠ21 +13.5 (c 0.75, CHCl3),7 the formal product from
D
Treatment of both the cis-fused 2 and cis-spiro 3
diacetonides with aqueous trifluoroacetic acid (TFA)
a similar procedure starting from L-psicose 16. Treat-
ment of the cis-diol 6 and trans-diol 8 diacetonides with
aqueous trifluoroacetic acid (TFA) gave, respectively,
pure samples of the unprotected branched allono-1222
and altrono-1323 lactones.
gave the deprotected branched talono-lactone 9;18
a
pure sample of the isomeric deprotected branched galac-
tono-lactone 1019 was obtained by reaction of the trans-
spiro 4 with aqueous TFA.
4. Summary
3. Branched chirons from D-psicose
The amounts of the spiro-cis-diol diacetonides derived
from tagatose and psicose in which the carbon side
chain at C-4 of the lactones is trans- to the new cis-diol
A similar procedure was adopted for the Kiliani reaction
of D-psicose 5 with sodium cyanide (Scheme 3), which

5758
R. Soengas et al. / Tetrahedron Letters 46 (2005) 5755–5759
7.0 Hz, H6), 4.26 (s, 1H, H3), 4.31–4.36 (m, 2H, H4, H5),
4.88 (br s, 1H, –OH); dC (CDCl3): 20.3, 25.2, 25.7, 28.8
(2 · –C(CH3)2), 62.2 (C-20), 65.7 (C-6), 68.7 (C-2), 74.7
(C-5), 75.6 (C-3), 81.0 (C-4), 98.7, 111.5 (2 · –C(CH3)2),
175.1 (C-1); m/z (NH3, ES+): 289 (M+H)+, HRMS calcd
for C13H20O7 [(M+H)+] 289.1287; found 289.1290.
unit are very much less than the corresponding materials
obtained in the Kiliani reactions of fructose and sorbose
where the side chain is cis. This makes the isolation of
the major products more convenient. There may be rela-
tively unfavourable steric repulsions when the cis-diol
acetonide and the C5,C6 side chain are on the same side
of the lactone ring; this is the case with the products
from fructose and sorbose, where such interactions
may cause greater production of the cis-spiro acetonides.
13. 2,3:5,6-Di-O-isopropylidene-2-C-hydroxymethyl-D-talono-
1,4-lactone 2: mp 109–111 ꢁC (diethyl ether/cyclohexane);
20
½aŠ À26.9 (c 1.4, chloroform); mmax (NaCl): 3454 (–OH),
D
1787 (–C@O) cmÀ1; dH (CDCl3): 1.33, 1.36, 1.46, 1.47
(4 · s, 12H, 2 · –C(CH3)2), 2.24–2.30 (m, 1H, –OH), 3.96–
4.00 (m, 3H, H6, H20, H200), 4.14 (dd, 1H, J6;6 8.4 Hz, J6 ;5
6.9 Hz, H60), 4.32–4.36 (m, 1H, H5), 4.52 (d, 1H, J4,5
0.7 Hz, H4), 4.76 (s, 1H, H3); dC (CDCl3): 25.3, 25.4, 26.6,
26.9 (2 · –C(CH3)2), 60.1 (C-20), 65.2 (C-6), 75.1 (C-5),
79.3 (C-3), 81.7 (C-4), 85.6 (C-2), 110.5, 113.4 (2 ·
–C(CH3)2), 174.5 (C-1); m/z (NH3, ES+): 289 (M+H)+;
Found: C 54.17, H 7.00; C13H20O7 requires C 54.16, H
6.99.
0
0
All the ketohexoses undergo efficient cyanohydrin exten-
sions and form at least some readily crystallised diaceto-
nides. The chirons described in this paper produce
branched THF derived scaffolds for a new class of sugar
amino acid.24
Acknowledgements
14. Harding, C. C.; Watkin, D. J.; Cowley, A. R.; Soengas,
R.; Skytte, U. P.; Fleet, G. W. J. Acta Cryst. 2005, E61,
o250–o252.
15. Shallard-Brown, H. A.; Harding, C. C.; Watkin, D. J.;
Soengas, R.; Skytte, U. P.; Fleet, G. W. J. Acta Crystal-
logr., Sect. E 2004, 60, o2163–o2164.
Financial support provided by the European Commu-
nityÕs Human Potential Programme under contract
HPRN-CT-2002-00173 and by the Xunta de Galicia is
gratefully acknowledged.
16. 2-C-tert-Butyldimethylsilyloxymethyl-2,3:5,6-di-O-isopro-
20
pylidene-D-talono-1,4-lactone 11: ½aŠ À5.5 (c 2.0, chloro-
D
form); mmax (NaCl): 1790 (–C@O) cmÀ1; dH (CDCl3): 0.09,
0.10 (2 · s, 6H, –Si(CH3)2), 0.92 (s, 9H, –SiC(CH3)3), 1.36,
1.44, 1.46 (3 · s, 12H, 2 · –C(CH3)2), 3.91–3.97 (m, 2H,
References and notes
0
00
1. Bols, M. Carbohydrate Building Blocks; John Wiley &
Sons: New York, 1996; Lichtenthaler, F. W.; Peter, S.
Compt. Rend. Chim. 2004, 7, 65–90.
2. Hudson, C. S. Adv. Carbohydr. Chem. 1945, 1, 2–36;
Hudson, C. S. J. Am. Chem. Soc. 1951, 73, 4498–4499;
Pratt, J. W.; Richtmyer, N. K.; Hudson, C. S. J. Am.
Chem. Soc. 1953, 75, 4503–4507.
3. Ferrier, R. J. J. Chem. Soc. 1962, 3544–3549.
4. Kiliani, H. Ber. Dtsch. Chem. Ges. 1885, 18, 3066–3072;
Kiliani, H. Ber. Dtsch. Chem. Ges. 1886, 19, 221–227;
Kiliani, H. Ber. Dtsch. Chem. Ges. 1928, 61, 1155–1169.
5. Woods, R. J.; Neish, A. C. Can. J. Chem. 1953, 31, 471–
475; Woods, R. J.; Neish, A. C. Can. J. Chem. 1954, 32,
404–414.
6. Gorin, P. A. J.; Perlin, A. S. Can. J. Chem. 1956, 36, 480–
485.
7. Hotchkiss, D. J.; Soengas, R.; Simone, M. I.; van Ameijde,
J.; Hunter, S.; Cowley, A. R.; Fleet, G. W. J. Tetrahedron
Lett. 2004, 45, 9461–9464.
8. Beadle, J. R.; Saunders, J. P.; Wajda, T. J. Process for
Manufacturing Tagatose. U.S. Patent 5,078796, January 7,
1992.
9. Skytte, U. P. Cereal Foods World 2002, 47, 224–227.
10. Granstrom, T. B.; Takata, G.; Tokuda, M.; Izumori, K.
J. Biosci. Bioeng. 2004, 97, 89–94; Izumori, K. Naturwis-
sennshaften 2002, 89, 120–124.
H6, H200), 4.03 (d, 1H, J2 ;2 11.2 Hz, H20), 4.13 (dd, 1H,
J6;6 12.0 Hz, J6 ;5 6.8 Hz, H60), 4.30–4.35 (m, 1H, H5),
4.48 (d, 1H, J4,5 2.8 Hz, H4), 4.74 (s, 1H, H3); dC (CDCl3):
À5.7, À5.4 (2 · –Si(CH3)2), 10.3 (–SiC(CH3)3), 25.5, 25.6,
26.5, 27.2 (2 · –C(CH3)2), 25.8 (–SiC(CH3)3), 60.8 (C-20),
65.3 (C-6), 75.4 (C-5), 79.1 (C-3), 81.9 (C-4), 86.3 (C-2),
110.4, 113.5 (2 · –C(CH3)2), 174.3 (C-1); m/z (NH3, ES+):
403 (M+H)+, HRMS calcd for C19H34O7Si [(M+H)+]
403.2152; found 403.2154.
0
0
17. 2,20:5,6-Di-O-isopropylidene-2-C-hydroxymethyl-D-galac-
tono-1,4-lactone 4: mp 126–128 ꢁC (diethyl ether/cyclo-
20
hexane); ½aŠ À53.7 (c 1.8, chloroform); mmax (NaCl): 3443
D
(–OH), 1790 (–C@O) cmÀ1; dH (CDCl3): 1.39, 1.43, 1.52,
1.59 (4 · s, 12H, 2 · –C(CH3)2), 2.69 (br s, 1H, –OH),
3.99–4.03 (m, 3H, H4, H60, H200), 4.14 (dd, 1H, J6,5 6.8 Hz,
0
J6;6 8.6 Hz, H6), 4.36–4.40 (m, 1H, H5), 4.51 (dd, 1H,
0
00
J3,OH 3.8 Hz, J3,4 8.2 Hz, H3), 4.61 (d, 1H, J2 ;2 8.7 Hz,
H20); dC (CDCl3): 25.3, 26.0, 26.3 (2 · –C(CH3)2), 64.8 (C-
20), 65.5 (C-6), 72.4 (C-3), 73.7 (C-5), 79.6 (C-4), 83.7 (C-
2), 110.2, 112.3 (2 · –C(CH3)2), 173.8 (C-1); m/z (NH3,
ES+): 289 (M+H)+; Found: C 54.18, H 7.00; C13H20O7
requires C 54.16, H 6.99.
18. 2-C-Hydroxymethyl-D-talono-1,4-lactone 9, oil, ½aŠ
21
D
À49.0 (c 3.1, in water); mmax (Ge IR plate): 3565 (–OH),
1769 (–C@O) cmÀ1; dH (D2O): 3.71 (d, 1H, J2 ;2 11.6 Hz,
0
00
H20), 3.72–3.76 (m, 2H, H6, H60), 3.82 (d, 1H, J2 ;2
0
00
11. Itoh, H.; Sato, I.; Izumori, K. J. Ferment. Bioeng. 1995,
80, 101–103; Takeshita, K.; Suga, A.; Takada, G.;
Izumori, K. J. Biosci. Bioeng. 2000, 90, 453–455; Itoh,
H.; Sato, T.; Takeuchi, T.; Anisur, R. K.; Izumori, K. J.
Ferment. Bioeng. 1995, 79, 184–185; Itoh, H.; Izumori, K.
J. Ferment. Bioeng. 1996, 81, 351–353.
11.6 Hz, H200), 3.94–3.97 (m, 1H, H5), 4.43–4.49 (m, 2H,
H4, H3); dC (D2O): 61.2 (C-6), 62.9 (C-20), 68.1, 70.1 (C-3,
C-5), 75.7 (C-2), 82.8 (C-4), 176.8 (C-1); m/z (NH3, ESÀ):
225 (MÀH+NH4)+; HRMS calcd for C7H11O7 [(MÀH)+]
207.0501; found 207.0505.
21
D
19. 2-C-Hydroxymethyl-D-galactono-1,4-lactone 10, oil, ½aŠ
12. 2,20:5,6-Di-O-isopropylidene-2-C-hydroxymethyl-D-tal-
À46.9 (c 1.1, water); mmax (Ge IR plate): 3563(–OH), 1768
(–C@O) cmÀ1; dH (D2O): 3.71–3.75 (m, 2H, H6, H60), 3.79
ono-1,4-lactone 3: mp 130–132 ꢁC (diethyl ether/cyclohex-
20
0
00
ane); ½aŠ +10.2 (c 1.2, chloroform); mmax (NaCl): 3377
(d, 1H, J2 ;2 11.8 Hz, H20), 3.89–3.92 (m, 1H, H5), 4.00 (d,
D
(–OH), 1776 (–C@O) cmÀ1; dH (CDCl3): 1.33, 1.38, 1.39,
1H, J2 ;2 11.6 Hz, H200), 4.41 (dd, 1H, J3,4 8.3 Hz, J4,5
2.7 Hz, H4), 4.51 (d, 1H, J3,4 8.3 Hz, H3); dC (D2O): 61.9
(C-6), 62.7 (C-20), 70.0, 74.5 (C-3, C-5), 78.7 (C-2), 81.5
(C-4), 178.3 (C-1); m/z (NH3, ESÀ): 225 (MÀH+NH4)+;
0
00
0
00
1.46 (4 · s, 12H, 2 · –C(CH3)2), 3.88 (d, 1H, J2 ;2 12.0 Hz,
H20), 4.05 (dd, 1H, J6;6 8.5 Hz, J6 ;5 8.2 Hz, H60), 4.10 (d,
0
0
1H, J2 ;2 12.0 Hz, H20); 4.18 (dd, 1H, J6;6 8.5 Hz, J6,5
0
00
0

R. Soengas et al. / Tetrahedron Letters 46 (2005) 5755–5759
5759
HRMS calcd for C7H11O7 [(MÀH)+] 207.0501; found
112.3 (2 · –C(CH3)2), 173.8 (C-1); m/z (NH3, ES+): 289
207.0504.
20. 2,3:5,6-Di-O-isopropylidene-2-C-hydroxymethyl-D-allono-1,
(M+H)+; Found: C 54.37, H 7.19; C13H20O7 requires C
54.16, H 6.99.
20
D
19
D
4-lactone 6: mp 132–134 ꢁC; ½aŠ À23.6 (c 1.0, chloroform);
22. 2-C-Hydroxymethyl-D-allono-1,4-lactone 12: ½aŠ +36.3
m
max (NaCl): 3198 (–OH), 1781 (–C@O) cmÀ1; dH (CDCl3):
(c 1.2, water); mmax (Ge IR plate): 3384 (–OH), 1770
1.36, 1.45, 1.47, 1.50 (4 · s, 12H, 2 · –C(CH3)2), 2.20
(dd, 1H, JOH;2 8.7 Hz, JOH;2 4.0 Hz, –OH), 3.92–4.04
(–C@O) cmÀ1; dH (D2O): 3.65–3.78 (m, 3H, H6, H60,
H20), 3.80 (d, 1H, J2 ;2 8.0 Hz, H200), 4.10–4.14 (m, 1H,
H5), 4.44 (dd, 1H, J3,4 7.0 Hz, J4,5 4.0 Hz, H4), 4.52 (d,
1H, J3,4 7.0 Hz, H3); dC (D2O): 61.4 (C-6), 62.2 (C-20),
67.5, 70.8 (C-3, C-5), 75.9 (C-2), 83.2 (C-4), 176.9 (C-1);
m/z (NH3, ESÀ): 207 (MÀH)+; HRMS calcd for C7H11O7
00
0
0
00
(m, 3H, H6, H20, H200), 4.17 (dd, 1H, J6;6 9.0 Hz, J6 ;5
6.8 Hz, H60), 4.30–4.35 (m, 1H, H5), 4.43 (d, 1H, J4,5
5.8 Hz, H4), 4.80 (s, 1H, H3); dC (CDCl3): 24.6, 26.3, 26.6,
26.9 (2 · –C(CH3)2), 61.3 (C-20), 66.1 (C-6), 73.9 (C-5),
78.5 (C-3), 83.6 (C-4), 85.4 (C-2), 110.6, 113.5 (2 ·
–C(CH3)2), 174.6 (C-1); m/z (NH3, ESÀ): 287 (MÀH)+;
Found: C 54.33, H 7.10; C13H20O7 requires C 54.16, H
6.99.
0
0
[(MÀH)+] 207.0501; found 207.0509.
20
23. 2-C-Hydroxymethyl-D-altrono-1,4-lactone 13: ½aŠ +32.8
D
(c 2.0, water); mmax (Ge IR plate): 3418 (–OH), 1769
(–C@O) cmÀ1; dH (D2O): 3.45 (d, 1H, J6,5 7.2 Hz, J6;6
0
21. 2,20:5,6-Di-O-isopropylidene-2-C-hydroxymethyl-D-altrono-
11.8 Hz, H6), 3.53–3.59 (m, 2H, H60, H20), 3.79 (d, 1H,
J2 ;2 11.5 Hz, H200), 3.90–3.93 (m, 1H, H5), 4.22 (dd, 1H,
J3,4 7.9 Hz, J4,5 3.5 Hz, H4), 4.35 (d, 1H, J3,4 7.9 Hz, H3);
0
00
1,4-lactone 8: mp 108–110 ꢁC (diethyl ether/cyclohexane);
19
½aŠ +4.5 (c 1, chloroform); mmax (NaCl): 3454 (–OH),
D
1791 (–C@O) cmÀ1; dH (CDCl3): 1.39, 1.43, 1.52, 1.59
(4 · s, 12H, 2 · –C(CH3)2), 2.69 (br s, 1H, –OH), 3.99–
d
C (D2O): 62.0, 62.1 (C-6, C-20), 71.1, 73.9 (C-3, C-5), 79.0
(C-2), 81.9 (C-4), 178.3 (C-1); m/z (NH3, ESÀ): 207
(MÀH)+; HRMS calcd for C7H11O7 [(MÀH)+] 207.0501;
found 207.0506.
4.03 (m, 3H, H4, H60, H200), 4.14 (dd, 1H, J6,5 6.8 Hz, J6;6
0
8.6 Hz, H6), 4.36–4.40 (m, 1H, H5), 4.51 (dd, 1H, J3,OH
3.8 Hz, J3,4 8.2 Hz, H3), 4.61 (d, 1H, J2 ;2 8.7 Hz, H20); dC
(CDCl3): 25.3, 26.0, 26.3 (2 · –C(CH3)2), 64.8 (C-20), 65.5
(C-6), 72.4 (C-3), 73.7 (C-5), 79.6 (C-4), 83.7 (C-2), 110.2,
24. Simone, M. I.; Soengas, R.; Newton, C. R.; Watkin, D. J.;
Fleet, G. W. J. Tetrahedron Lett. 2005, 46, following
paper, doi:10.1016/j.tetlet.2005.06.029.
0
00