Synthesis of thiazole analogues of the immunosuppressive agent (1R,25,3A)-2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazole

Article abstract of DOI:10.1039/a903675j

The synthesis of four of the diastereoisomers of 2-acetyl-5-(l ,2,3,4-tetrahydroxybutyl)thiazole and two of the diastereoisomers of 2-acetyl-5-( 1,2,3,4,5-pentahydroxypentyl)thiazole and 2-acetyl-4-( 1,2,3,4,5-pentahydroxypentyl)thiazole are reported. These syntheses involve the condensation of 5- or 4-metallated 2-( 1,1 -dimethoxyethyl)thiazoles with 2,3-O-isopropylidene-D-erythrono-l,4-lactone or 5-O-(tert-butyldimethylsilyl)-2,3-O-isopropylideneD-ribonolactone followed by reductive ring-opening of the resulting lactols. The stereochemistries and structures of some key compounds have been determined by single crystal X-ray structural analysis.

Full text of DOI:10.1039/a903675j

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Synthesis of thiazole analogues of the immunosuppressive agent
(1R,2S,3R)-2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazole
George R. Jeoffreys,a Alison T. Ung,a Stephen G. Pyne,*a Brian W. Skeltonb and
Allan H. Whiteb
a Department of Chemistry, University of Wollongong, Wollongong, NSW, 2522, Australia
b Department of Chemistry, University of Western Australia, Nedlands, WA, 6907, Australia
Received (in Cambridge) 7th May 1999, Accepted 23rd June 1999
The synthesis of four of the diastereoisomers of 2-acetyl-5-(1,2,3,4-tetrahydroxybutyl)thiazole and two of the
diastereoisomers of 2-acetyl-5-(1,2,3,4,5-pentahydroxypentyl)thiazole and 2-acetyl-4-(1,2,3,4,5-pentahydroxy-
pentyl)thiazole are reported. These syntheses involve the condensation of 5- or 4-metallated 2-(1,1-dimethoxyethyl)-
thiazoles with 2,3-O-isopropylidene--erythrono-1,4-lactone or 5-O-(tert-butyldimethylsilyl)-2,3-O-isopropylidene-
-ribonolactone followed by reductive ring-opening of the resulting lactols. The stereochemistries and structures of
some key compounds have been determined by single crystal X-ray structural analysis.
As part of an ongoing medicinal chemistry project1–6 we
required the synthesis of the 4- and 5-thiazole analogues, 2
and 3 respectively, of the known immunosuppressive agent,
Fig. 1 Compound 7b.
was then treated with 2,3-O-isopropylidene--erythrono-1,4-
(1R,2S,3R)-2-acetyl-4(or 5)-(1,2,3,4-tetrahydroxybutyl)imid-
lactone 6 at the same temperature for 1.5 h. Quenching the
azole (THI) 1.7–9 THI is a minor component of the common
reaction mixture at Ϫ78 ЊC, followed by column chromatog-
raphy, gave the lactols 7a,b in 62% yield as a 95:5 mixture of
diastereoisomers, along with a small amount (7%) of the C-2
food additive Caramel Colour III. THI has been found to cause
lymphopenia (depression of blood lymphocyte counts), with-
out any apparent side-effects, in mice and rats that have
epimerized ketone 8 (Scheme 1). The amount of ketone 8
formed increased upon increasing the reaction temperature. For
example, warming the reaction mixture to rt over 1 h, prior to
quenching resulted in a 2:1 mixture of 7 and 8, respectively.
The stereochemistry of the ketone 8 will be discussed later in
this paper.
In solution (CDCl3) the major lactol isomer was 7a from
NOESY experiments that showed significant cross-peaks
between H4Ј of the thiazole ring and H2 of the dihydrofuran
ring (Scheme 1). Surprisingly, crystallization of this lactol mix-
ture gave single crystals of lactol 7b, as characterized by a single
crystal X-ray study, which was expected to be thermodynamic-
ally less favoured than 7a since the thiazole ring is syn to the
sterically demanding 1,3-dioxolane ring. A projection of the
structure of 7b is shown in Fig. 1. It is possible that in the solid
state intermolecular H-bonding favours formation of lactol 7b
over 7a.
been given THI in their drinking water.7,8 Thus THI and its
analogues have potential applications as an immunosuppressive
agent in organ transplant biology or for preventing the onset of
diabetes.9
Our general strategy for the synthesis of thiazole analogues
of THI involves the condensation of 5- or 4-metallated
2-(1,1-dimethoxyethyl)thiazole with 2,3-O-isopropylidene--
erythrono-1,4-lactone 6 or 5-O-(tert-butyldimethylsilyl)-2,3-O-
isopropylidene--ribonolactone 21 followed by reductive
ring-opening of the resulting lactols. The synthesis of four
diastereoisomers of compound 2 (n = 1) has been reported as a
communication.5 We now report the details of this work and
the synthesis of some pentahydroxypentyl analogues 2 (n = 2)
and 3 (n = 2) and X-ray structures to support the stereo-
chemical assignments made to the individual diastereoisomers.
Synthesis of 2-acetyl-5-(1,2,3,4-tetrahydroxybutyl)thiazoles
Reductive ring opening of 7 with sodium borohydride in
methanol at Ϫ10 ЊC afforded a 9:1 mixture of the diols 9 and
10 that could be readily separated by column chromatography.
The stereochemistry of these diols was also determined by
Commercially available 2-acetylthiazole 4 was converted to its
dimethoxyketal 5 in 80% yield, using standard conditions. The
5-lithiothiazole derivative of 5 was generated at Ϫ78 ЊC and
J. Chem. Soc., Perkin Trans. 1, 1999, 2281–2291
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Fig. 2 Compound 9 (showing molecules 1 and 2).
Fig. 3 Compound 10.
Scheme 1
X-ray crystallography (Figs. 2 and 3). The stereochemistry of
the major diol 9 is that predicted by the Felkin–Anh transition
model (A)10–13 or the γ-chelated transition state model B,14 in
which hydride attack would be expected to occur from the con-
vex face of the bicyclo[5.3.0]decane ring system in B (Fig. 4).
Acid hydrolysis of the individual diastereoisomers 9 and 10
gave the tetrols 11 and 12, respectively. Although, compound 11
had identical spectral properties to that obtained for 11 from
our previous synthesis, the specific rotation of 11 from this
work, [α]D25 ϩ18.3 (c 0.6, H2O), was considerably higher than that
obtained previously {[α]D25 ϩ7.7 (c 0.34, H2O)} using a different
synthetic route.3
Fig. 4
To examine the effect of the C4 hydroxy or alkoxy group on
the reduction of the lactol 7, and to test the likelihood of the
transition states A and B, diol 9 was converted in two steps to
the ketone 13 (Scheme 2). This ketone was different to the
ketone 16 obtained from either the direct silylation of the
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Scheme 2
hydroxy-ketone 8 with tert-butylchlorodimethylsilane (TBSCl)–
imidazole or by
a ring-opening–silylation–epimerization
sequence on the lactol 7 using TBSCl and the stronger base
triethylamine (Scheme 3). The latter reaction was very slow, the
Fig. 5 Compound 17 (showing molecules 1 and 2).
gave nearly equal proportions of the diols 14 and 15 (Scheme
2). The structures of 14 and 15 were confirmed by their conver-
sion to 9 and 10 respectively, by desilylation with tetrabutyl-
ammonium fluoride in THF. The poor diastereoselectivity in
the reductions of 13 can be understood in terms of the transi-
tion state model C in which the OTBS group and the C2 methyl
group on the 1,3-dioxolane ring, sterically hinder attack of
hydride from the Si and Re faces of the carbonyl group, respect-
ively. Thus, the free hydroxy group in transition state structures
A and B, which can potentially coordinate the reducing
agent, appears to be essential for obtaining a high degree of
diastereoselectivity.
Reduction of the keto group of the 4-O-silylated cis-1,3-
dioxolane 16 with a number of reducing agents (NaBH4,
DIBAL, Red-Al, K-Selectride and L-Selectride) gave mixtures
of the diastereoisomeric alcohols 17 and 18. The optimum
diastereoselectivity was obtained (17:18 = 84:16) when L-
Selectride was employed at Ϫ78 ЊC. The stereochemistry
assigned to 17 was unequivocally determined by an X-ray study
(Fig. 5) and is that expected from the Felkin–Ahn transition
state model D. Acid hydrolysis of the individual diastereo-
isomers 17 and 18 gave the tetrols 19 and 20, respectively.
Synthesis of 2-acetyl-4-(1,2,3,4,5-pentahydroxypentyl)- and
2-acetyl-5-(1,2,3,4,5-pentahydroxypentyl)-thiazoles
Scheme 3
low yield of 16 (48%) obtained being due to the presence of
unreacted starting material. NOESY experiments on 16 showed
significant cross peaks between H2 and the β-Me of the
dioxolane ring and between H3 and the α-Me of the dioxolane
ring and thus revealed the trans-1,3-dioxolane structure.
In contrast to 7, the reduction of the keto group of the 4-O-
silylated cis-1,3-dioxolane 13, was poorly diastereoselective and
The 5-lithiothiazole derivative of 5 was treated with 5-O-(tert-
butyldimethylsilyl)-2,3-O-isopropylidene--ribonolactone 2115
at Ϫ78 ЊC for 1.5 h to give the lactol 22, as a single isomer in
64% yield (Scheme 4). In contrast to the corresponding reaction
of lithiated 5 with lactone 6, no ring-opening ketone products
were observed. X-Ray analysis of 22 showed it had the same
relative stereochemistry as 7b with respect to the thiazole and
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Fig. 6 Compound 22.
Fig. 7 Compound 24.
Fig. 8 Compound 27.
TBSOCH2 group which should occupy a pseudo-equatorial
position. Acid hydrolysis of the individual diastereoisomers 23
and 24 gave the pentols 25 and 26, respectively, in good yields,
which were converted to their corresponding pentaacetates 27
and 28 respectively, under standard conditions.4 The stereo-
chemistry of 24 and 27 was confirmed by single crystal X-ray
analysis (Figs. 7 and 8).
4-Bromo-2-(1,1-dimethoxyethyl)thiazole6 underwent trans-
metallation at Ϫ78 ЊC and was then treated with the lactone 21
at Ϫ78 ЊC for 1.5 h (Scheme 5). Purification of the reaction
mixture by column chromatography gave the desired lactol
29 (dr = 69:31) in 44% yield and surprisingly the isomeric
5-thiazole adduct 22 in 15% yield (Scheme 5). The latter com-
pound must have arisen through formation of the more stable
5-lithiated thiazole derivative. Reduction of 29 with sodium
borohydride in methanol at Ϫ10 ЊC afforded a 60:40 mixture
of the diols 30 and 31, respectively. Separation of this mixture
by column chromatography gave diastereomerically pure 31
and 32 in 30% and 21% yields, respectively. The stereochemistry
of 30 was secured by single crystal X-ray analysis (Fig. 9).
Compounds 30 and 31 were converted to their pentols 32 and
33 respectively by acid hydrolysis. Small samples of these pen-
tols were converted to their respective pentaacetates, 34 and 35.
Scheme 4
1,3-dioxolane rings (Fig. 6). Reduction of 22 with sodium
borohydride in methanol at Ϫ10 ЊC afforded a mixture of the
diols 23 and 24. These could be isolated in diastereomerically
pure form in 48% and 46% yields, respectively, by column
chromatography. Attempts to reductively ring-open the lactol
22 with other reducing agents (e.g. DIBAL and L-Selectride)
were unsuccessful and only starting lactol 22 was recovered.
The poor diastereoselectivity in the reduction of 22 is in stark
contrast to that found for the lactol 7 and is unexpected based
on the transition state structures A and B. The corresponding
transition state structures E and F for the reduction of ring-
opened 22 do not appear to be made unfavourable by the extra
1
The H NMR analysis of the tetraacetate of THI (1) and its
C1 epimer4 and of the diastereomeric pairs 27 and 28 and 34
and 35 showed that H1, in compounds with the (1R)-stereo-
chemistry (tetraacetate of 1, 27 and 34), comes further
downfield of H1 in their respective isomers having the (1S)-
stereochemistry. Furthermore, J1,2 is generally smaller in the 1R
diastereoisomer.
In conclusion, we have developed a short, efficient and
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penia in mice, while the pentol 25 showed a slightly higher activ-
ity at the same concentration.
Experimental
General procedures were as described previously.1,3,6 Unless
otherwise indicated, all NMR spectra were recorded in CDCl3
solution at 300 MHz (1H NMR) or 77.5 MHz (13C NMR).
All melting points are uncorrected. 2-Acetyl thiazole and 2,3-
O-isopropylidine--erythronolactone
2 were commercially
available.
2-(1,1-Dimethoxyethyl)thiazole 5
To a solution of 2-acetylthiazole 4 (1 cm3, 9.5 mmol) in dry
methanol (30 cm3) was added trimethyl orthoformate (11.16
cm3, 95 mmol) and toluene-p-sulfonic acid (1.63 g). The mixture
was heated under reflux for 24 h. After cooling the reaction
mixture was poured into a separating funnel containing a satur-
ated solution of sodium bicarbonate (60 cm3). The aqueous
layer was extracted with ether. The combined organic extracts
were washed with 1 M sodium hydroxide (40 cm3), a saturated
aqueous solution of sodium chloride (40 cm3) and dried over
magnesium sulfate. The solvent was removed to give a dark
yellow oil which was purified by column chromatography (25%
ethyl acetate–hexane) to give 5 (1.31 g, 80%) as a yellow oil;
δH 7.80 (d, 1H, J 3.2, 4-H), 7.30 (1H, d, J 3.2, 5-H), 3.23 (6H, s,
2 × OCH3), 1.71 (3H, s, CH3); δC 171.62 (C), 142.50 (CH),
119.55 (C), 100.70 (C), 49.01 (CH3), 23.86 (CH3); m/z (ES ϩve)
173.6 (M ϩ H, 50%).
Fig. 9 Compound 30.
2,3-O-Isopropylidene-1-[2-(1,1-dimethoxyethyl)thiazol-5-yl)]-ꢀ-
D-furanose 7
To a cooled solution of the thiazole 5 (0.409 g, 2.37 mmol) in
dry tetrahydrofuran (THF, 15 cm3) at Ϫ78 ЊC was added drop-
wise a solution of n-butyllithium (1.63 cm3, 2.61 mmol of a 1.6
M solution in n-hexane). The resulting mixture was left to stir at
Ϫ78 ЊC for 40 min, then a solution of 2,3-O-isopropylidene--
erythronolactone (0.410 g, 2.596 mmol) in dry THF (10 cm3)
was added slowly to the mixture and stirring was continued
for 1.5 h. The reaction mixture was poured into a saturated
solution of ammonium chloride (50 cm3) and the aqueous
layer was extracted with ethyl acetate (3 × 50 cm3). The com-
bined organic extracts were washed with a saturated solution
of sodium chloride and dried over magnesium sulfate. The
solvent was removed to give a thick yellow oil which was puri-
fied by column chromatography (30% ethyl acetate–hexane)
to give 7 (0.487 g, 62%) as a white solid and 8 (0.054 g, 7%) as
a colourless oil.
7: mp 114–115 ЊC; [α]D28 Ϫ32.73 (c 2.3, CHCl3) (Found: C,
50.65; H, 6.44; N, 4.16; S, 9.72. C14H21O6NS requires C,
50.74; H, 6.39; N, 4.23; S, 9.68%); δH 7.85 (1H, d, J 0.9, 4-H),
4.98 (1H, dd, J 3.9 and 5.7, 2Ј-H), 4.61 (1H, d, J 5.4, 3Ј-H),
4.16 (1H, dd, J 3.6 and 10.2, CHaHb), 4.08 (1H, d, J 10.5,
CHaHb), 3.26 (3H, s, OCH3), 3.22 (3H, s, OCH3), 1.72 (3H,
s, CH3), 1.47 (3H, s, CH3CCH3), 1.29 (3H, s, CH3CCH3);
δC 173.42 (C), 140.89 (CH), 138.50 (C), 112.84 (C), 104.62 (C),
100.86 (C), 85.81 (CH), 80.75 (CH), 71.04 (CH2), 49.33
(OCH3), 49.30 (OCH3), 26.13 (CH3), 24.72 (CH3), 23.99
(CH3); m/z (ES ϩve) 332.1 (M ϩ H, 100%), 300.5 (M Ϫ OCH3,
100).
Scheme 5
diastereoselective synthesis of the (1S,2S,3R)- and (1R,2R,3R)-
5-thiazole analogues of the bioactive molecule THI from a
common precursor, the lactol 3. This methodology is comple-
mentary to the Sharpless asymmetric dihydroxylation method
for the diastereoselective synthesis of the syn-1,2-diol moiety of
THI and its analogues that have opposite stereochemistries at
C-1 and C-2.4,6 Extension of this methodology to prepare the
pentahydroxypentyl 4-thiazole and 5-thiazole analogues was
also efficient but the diastereoselectivity of the reductive ring-
opening steps were poorly diastereoselective. Furthermore, this
approach should be applicable to the diastereoselective syn-
thesis of other polyhydroxylated bioactive molecules. Prelimin-
ary experiments on these analogues suggested that compound
11, the 5-thiazole analogue of THI, had essentially the same
activity versus concentration profile as THI in causing lympho-
8: [α]D28 18.78 (c 1.4, CHCl3); δH 8.73 (1H, s, 4-H), 4.77 (1H, d,
J 7.2, 2Ј-H), 4.39 (1H, ddd, J 3.9, 3.9, 7.2 Hz, 3Ј-H), 3.98 (1H,
ddd, J 3.0, 3.0 and 12.2, CHaHb), 3.74 (1H, ddd, J 3.6, 8.1 and
12.15, CHaHb), 3.26 (3H, s, OCH3), 3.25 (3H, s, OCH3), 1.72
(3H, s, CH3), 1.54 (3H, s, CH3CCH3), 1.43 (3H, s, CH3CCH3);
δC 191.82 (C), 179.82 (C), 149.99 (CH), 136.78 (C), 111.27 (C),
100.98 (C), 80.13 (CH), 78.62 (CH), 61.93 (CH2), 49.54
(2 × OCH3), 26.80 (CH3), 26.03 (CH3), 23.83 (CH3); m/z (ES
ϩve) 331.8 (M ϩ H, 20%), 300.4 (M Ϫ OCH3).
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2-(1,1-Dimethoxyethyl)-5-[(1S,2R,3R)- and (1R,2R,3R)-2,3-
isopropylidenedioxy-1,4-dihydroxybutyl]thiazole 9 and 10
248.4 (M ϩ 1, 100%) (Found: M ϩ H, 248.059270. C9H14NO5S
requires 248.059246).
To the solution of the α-hemiacetal 7 (0.299 g, 0.88 mmol) in
dry methanol (25 cm3) at Ϫ10 ЊC was added portionwise solid
sodium borohydride (0.37 g, 8.80 mmol). The reaction mixture
was left to stir at Ϫ10 ЊC for 1.5 h. The solvent was removed
and the residue was dissolved in water (30 cm3) and the aqueous
layer was extracted with ethyl acetate (3 × 50 cm3). The com-
bined organic extracts were dried over sodium sulfate. The
solvent was removed under reduced pressure to give a clear oil
that eventually solidified as a white solid. The white solid was
purified by column chromatography (75% ethyl acetate–
hexane) to give 9 (0.182 g, 62%) and 10 (0.018 g, 6%) as white
solids.
2-(1,1-Dimethoxyethyl)-5-[(2R,3R)-4-tert-butyldimethyl-
silyloxy-1-oxo-2,3-isopropylidenedioxybutyl]thiazole 13
To the cold solution of diol 9 (0.518 g, 1.55 mmol) in dry
tetrahydrofuran–dimethylformamide (3:1, 5 cm3) at 0 ЊC was
added tert-butylchlorodimethylsilane (0.24 g, 1.59 mmol) and
imidazole (0.224 g, 3.294 mmol). The reaction mixture was left
to stir at room temperature for 1 h then was diluted with
dichloromethane–diethyl ether (2:1, 50 cm3). The organic layer
was washed with a solution of 1 M hydrochloric acid (50 cm3), a
saturated solution of sodium bicarbonate (50 cm3), a saturated
solution of sodium chloride (50 cm3) and dried over magnesium
sulfate. The solvent was removed under reduced pressure to give
a pale yellow oil which was purified by flash-column chrom-
atography to give a colourless oil (0.628 g, 90%). To a solution
of this oil (0.628 g, 1.41 mmol) in dry dichloromethane (30 cm3)
was added pyridinium dichromate (1.66 g, 4.43 mmol) and 4 Å
powdered molecular sieves (1 g). After stirring at room tem-
perature for 18 h, the reaction mixture was filtered through a
small pad of Celite and washed with dichloromethane (50 cm3).
The combined organic filtrates were washed with a cold solu-
tion of 1 M hydrochloric acid, a saturated solution of sodium
bicarbonate and dried over magnesium sulfate. The solvent was
removed to give a pale yellow oil which was purified by flash-
column chromatography (45% ethyl acetate–hexane) to give 13
as a colourless oil (0.510 g, 82%); δH 8.62 (1H, s, 4-H), 5.00 (1H,
d, J 7.8, 2Ј-H), 4.55 (1H, t, J 3.9, 3Ј-H), 3.71 (2H, d, J 3.9, CH2),
3.25 (3H, s, OCH3), 3.24 (3H, s, OCH3), 1.68 (3H, s, CH3),
1.64 (3H, s, CH3CCH3), 1.41 (3H, s, CH3CCH3), 0.68 (9H, s,
C(CH3)3), Ϫ0.18 (3H, s, CH3SiCH3), Ϫ0.20 (3H, s, CH3-
SiCH3); δC 190.16 (C), 178.54 (C), 148.63 (CH), 137.96 (C),
110.26 (C), 101.02 (C), 79.94 (CH), 79.44 (CH), 61.24 (CH2),
49.45 (OCH3), 49.42 (OCH3), 26.48 (CH3), 25.63 (CH3), 24.73
(CH3), 24.01 (CH3), 18.20 (C), Ϫ5.82 (CH3), Ϫ6.01 (CH3);
MS m/z (ES ϩve) 446.2 (M ϩ H, 100%), 414.2 (M Ϫ OCH3,
90) (Found: M ϩ H, 446.203263. C20H36NO6SSi requires
446.203217).
9: [α]D27 Ϫ18.21 (c 2.8, CHCl3) (Found: C, 50.42; H, 6.99, N,
4.16; S, 9.68. C14H23NO6S requires C, 50.44; H, 6.95; N, 4.20; S,
9.62%); δH 7.76 (1H, d, J 0.6, 4-H), 5.13 (1H, dd, J 4.5 and 9.0,
1Ј-H), 4.38 (1H, dd, J 3.9 and 6.6, 2Ј-H), 4.29 (1H, ddd, J 6.9,
4.8 and 4.8, 3Ј-H), 3.81 (1H, ddd, J 0.9, 4.2 and 6.3, CHaHb),
3.81 (1H, d, J 2.1, CHaHb), 3.35 (1H, d, J 4.2, CH2OH), 3.26
(3H, s, OCH3), 3.24 (3H, s, OCH3), 2.23 (1H, dd, J 5.1 and 5.1,
CЈ(1)OH), 1.72 (3H, s, CH3), 1.57 (3H, s, CH3CCH3), 1.43 (3H,
s, CH3CCH3); δC 172.67 (C), 140.38 (CH), 139.59 (C), 108.88
(C), 100.92 (C), 79.86 (CH), 78.50 (CH), 66.15 (CH), 60.22
(CH2), 49.38 (2 × OCH3), 26.85 (CH3), 24.96 (CH3), 24.09
(CH3); m/z (ES ϩve) 333.7 (M ϩ H, 70%), 302.00 (M Ϫ OCH3,
100).
10: mp 83–84 ЊC; [α]D25 Ϫ37.3 (c 1.16, CHCl3) (Found: C,
50.44; H, 6.98; N, 4.24; S, 9.58. C14H23NO6S requires C, 50.44;
H, 6.95; N, 4.20; S, 9.62%); δH 7.76 (1H, s, 4-H), 5.12 (1H, dd,
J 3.6 and 9.0, 1Ј-H), 4.38 (1H, ddd, J 3.9, 5.4 and 7.2, 2Ј-H),
4.26 (1H, dd, J 5.4 and 8.7, 3Ј-H), 3.99 (1H, ddd, J 4.5, 7.2 and
11.6, CHaHb), 3.88 (1H, ddd, J 4.2, 6.9 and 11.1, CHaHb),
3.26 (3H, s, OCH3), 3.25 (3H, s, OCH3), 1.72 (3H, s, CH3), 1.45
(3H, s, CH3CCH3), 1.35 (3H, s, CH3CCH3); δC 172.14 (C),
141.50 (C), 139.72 (CH), 108.83 (C), 100.91 (C), 80.28 (CH),
77.13 (CH), 66.67 (CH), 60.32 (CH2), 49.39 (CH3), 49.37 (CH3),
27.90 (CH3), 25.27 (CH3), 24.18 (CH3); m/z (ES ϩve) 334.3
(M ϩ H, 60%), 302.00 (M Ϫ OCH3, 100).
2-(1,1-Dimethoxyethyl)-5-[(2S,3R)-4-tert-butyldimethyl-
silyloxy-1-oxo-2,3-isopropylidenedioxybutyl]thiazole 16
(1ЈS,2ЈR,3ЈR)-2-Acetyl-5-(1,2,3,4-tetrahydroxybutyl)thiazole 11
Diol 9 (0.198 g, 0.594 mmol) was dissolved in acetone–water (17
cm3, 1:1) and conc. hydrochloric acid (5 cm3) was added drop-
wise to the solution. After stirring at room temperature for 2 h,
acetone was removed under reduced pressure and the aqueous
layer was washed with ether. Water was removed under high
vacuum to give 11 as a dark yellow hygroscopic solid (0.164 g,
97.3%); [α]D25 ϩ18.3 (c 0.6, H2O) [lit.,3 [α]D23 7.7 (c 0.34, H2O)];
δH (D2O) 7.82 (1H, s, 4-H), 5.25 (1H, s, 1Ј-H), 3.69 (2H, m, 2Ј-H
and 3Ј-H), 3.49 (2H, m, CHaHb), 2.51 (3H, s, CH3); δC (D2O)
192.71 (C), 165.04 (C), 149.01 (C), 140.04 (CH), 73.14 (CH),
70.32 (CH), 66.06 (CH), 62.41 (CH2), 25.28 (CH3); m/z (ES
Ϫve) 282.3 (M ϩ ClϪ, 100%) (Found: M ϩ H, 248.059270.
C9H14NO5S requires 248.059246).
Method A. To a solution of ketone 8 (0.65 g, 0.196 mmol) in
dry tetrahydrofuran–dimethylformamide (3:1, 6 cm3) at 0 ЊC
was added tert-butylchlorodimethylsilane (0.30 g) and imid-
azole (0.28 g). After stirring at room temperature for 1 h, the
reaction mixture was diluted with dichloromethane–diethyl
ether (2:1, 50 cm3). The organic layer was washed with a solu-
tion of 1 M hydrochloric acid (50 cm3). The acid layer was
back-extracted with dichloromethane (50 cm3). The combined
organic extracts were washed with a saturated solution of
sodium bicarbonate (50 cm3), a saturated solution of sodium
chloride and dried over magnesium sulfate. The solvent was
removed under reduced pressure to give a pale yellow oil
which was purified by flash-column chromatography (45%
ethyl acetate–hexane) to give 16 as a colourless oil (0.786 g,
90%).
(1ЈR,2ЈR,3ЈR)-2-Acetyl-5-(1,2,3,4-tetrahydroxybutyl)thiazole 12
To the solution of diol 10 (50 mg, 0.15 mmol) in acetone–water
(4.4 cm3, 1:1) was added dropwise conc. hydrochloric acid (0.22
cm3). After stirring at room temperature for 2 h, acetone was
removed under reduced pressure and the aqueous layer was
washed with ether. Water was removed under high vacuum to
give 12 as a dark yellow solid (40 mg, 94%); [α]D25 Ϫ58.62 (c 1.45,
H2O); δH (D2O) 7.81 (s, 1H, 4-H), 5.17 (1H, d, J 3.9, 1Ј-H), 3.76
(1H, dd, J 4.2 and 8.4, 2Ј-H), 3.54 (dd, 1H, J 2.7 and 11.7,
3Ј-H), 3.43 (1H, dd, J 5.7 and 11.7, CHaHb), 3.31 (1H, ddd,
J 3.0, 6.0 and 8.1 CHaHb), 2.49 (3H, s, CH3); δC (D2O) 193.84
(C), 166.22 (C), 145.72 (C), 142.27 (CH), 72.78 (CH), 71.25
(CH), 67.72 (CH), 62.22 (CH2), 25.28 (CH3); m/z (ES ϩve)
Method B. To the solution of lactol 7 (0.10 g, 0.3 mmol) in
dry dichloromethane (10 cm3) was added triethylamine (0.1
cm3), 4-dimethylaminopyridine (1.5 mg) and tert-butylchloro-
dimethylsilane (70 mg). The reaction mixture was left to stir at
room temperature over 2 days then was diluted with dichloro-
methane (20 cm3). The organic layer was washed with a satur-
ated solution of sodium chloride and dried over magnesium
sulfate. The solvent was removed to give a dark yellow oil which
was purified by flash-column chromatography (45% ethyl
acetate–hexane) to give 16 (50 mg, 48%) as a colourless oil;
δH 8.69 (1H, s, 4-H), 4.87 (1H, d, J 7.2, 2Ј-H), 4.32 (1H, ddd,
2286
J. Chem. Soc., Perkin Trans. 1, 1999, 2281–2291

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J 3.6, 3.6 and 7.2, 3Ј-H), 3.93 (1H, dd, J 3.6 and 11.4, CHaHb),
3.81 (1H, dd, J 3.6 and 11.4, CHaHb), 3.26 (6H, s, 2 × OCH3),
1.72 (3H, s, CH3), 1.51 (3H, s, CH3CCH3), 1.45 (3H, s,
CH3CCH3), 0.89 (9H, s, C(CH3)3), 0.80 (3H, s, CH3SiCH3), 0.75
(3H, s, CH3SiCH3); δC 191.60 (C), 179.50 (C), 149.50 (CH),
137.12 (C), 112.80 (C), 100.98 (C), 79.79 (CH), 79.32 (CH),
62.44 (CH2), 49.54 (2 × OCH3), 26.89 (CH3), 26.30 (CH3), 25.84
(CH3), 23.89 (CH3), 18.32 (C), Ϫ5.32 (CH3), Ϫ5.47 (CH3);
m/z (ES ϩve) 446.0 (M ϩ H, 30%), 414 (100) (Found: M ϩ H,
446.203263. C20H36NO6SSi requires 446.203217).
18.27 (C), Ϫ5.50 (CH3), Ϫ5.53 (CH3); m/z (ES ϩve) 448.2
(M ϩ H, 85%), 416.2 (M Ϫ OCH3, 100).
2-(1,1-Dimethoxyethyl)-5-[(1R,2R,3R)-2,3-isopropylidene-
dioxy-1-hydroxy-4-(tert-butyldimethylsilyloxy)butyl]thiazole
15. Oil; [α]D26 Ϫ25.08 (c 3.05, CH2Cl2); δH 7.79 (1H, d, J 0.6, 4-H),
5.08 (1H, ddd, J 0.6, 3.3 and 9.0, 1Ј-H), 4.80 (1H, d, J 3.3, 2Ј-H),
4.35–4.25 (2H, m, 3Ј-H and OH), 3.91 (1H, dd, J 9.6 and 10.8,
CHaHb), 3.71 (1H, dd, J 3.3 and 10.5, CHaHb), 3.26 (3H, s,
OCH3), 3.24 (3H, s, OCH3), 1.71 (3H, s, CH3), 1.40 (3H, s,
CH3CCH3), 1.31 (3H, s, CH3CCH3), 0.92 (9H, s, C(CH3)3), 0.15
(3H, s, CH3SiCH3), 0.14 (3H, s, CH3SiCH3); δC 171.29 (C),
140.16 (C), 140.04 (CH), 108.84 (C), 100.99 (C), 80.99 (CH2),
76.99 (CH), 66.66 (CH), 61.72 (CH2), 49.32 (CH3), 49.26
(CH3), 27.91 (CH3), 25.67 (CH3), 25.20 (CH3), 24.08 (CH3),
18.10 (C), Ϫ5.67 (CH3), Ϫ5.69 (CH3); m/z (ES ϩve) 448.2
(M ϩ H, 90%), 416.2 (M Ϫ OCH3, 100) (Found: M ϩ H,
448.218914. C20H38NO6SSi requires 448.218865).
2-(1,1-Dimethoxyethyl)-5-[(1R,2S,3R)-2,3-isopropylidene-
dioxy-1-hydroxy-4-(tert-butyldimethylsilyloxy)butyl]thiazole
17. Mp 79–80 ЊC; [α]D22 Ϫ6.26 (c 1.95, CH2Cl2) (Found: C, 53.90;
H, 8.68; N, 3.13; S, 7.32. C20H37NO6SSi requires C, 53.66; H,
8.33; N, 3.13; S, 7.16%); δH 7.74 (1H, d, J 0.6, 4-H), 5.05 (1H,
ddd, J 0.6, 4.5 and 7.8, 1Ј-H), 4.20 (1H, dd, J 4.5 and 7.8, 2Ј-H),
3.92 (1H, ddd, J 4.2, 6.6 and 7.8, 3Ј-H), 3.61 (1H, dd, J 4.5 and
6.3, CHaHb), 3.49 (1H, d, J 7.8, CHaHb), 3.26 (3H, s, OCH3),
3.24 (3H, s, OCH3), 1.71 (3H, s, CH3), 1.58 (3H, s, CH3CCH3),
1.42 (3H, s, CH3CCH3), 0.89 (9H, s, C(CH3)3), 0.06 (3H, s,
CH3SiCH3), 0.056 (3H, s, CH3SiCH3); δC 172.20 (C), 140.35
(CH), 139.35 (C), 109.86 (C), 100.92 (C), 81.61 (CH), 77.21
(CH), 67.96 (CH), 63.46 (CH2), 49.35 (CH3), 49.32 (CH3), 27.03
(CH3), 27.05 (CH3), 25.79 (CH3), 24.05 (CH3), 18.34 (CH3),
Ϫ5.59 (CH3), Ϫ5.60 (CH3); m/z (ES ϩve) 448.0 (M ϩ H, 100%),
416.0 (M Ϫ OCH3, 70).
2-(1,1-Dimethoxyethyl)-5-[(1S,2S,3R)-2,3-isopropylidene-
dioxy-1-hydroxy-4-(tert-butyldimethylsilyloxy)butyl]thiazole
18. Oil; [α]D23 ϩ6.63 (c 2.35, CH2Cl2); δH 7.74 (1H, s, 4-H), 4.96
(1H, d, J 4.5, 1Ј-H), 4.07 (1H, br s, 2HЈ), 3.97 (1H, dd, J 1.8 and
5.4, 3HЈ), 3.78 (1H, dd, J 3.3 and 10.2, CHaHb), 3.65–3.60 (1H,
m, CHaHb), 3.25 (3H, s, OCH3), 3.23 (3H, s, OCH3), 1.71
(3H, s, CH3), 1.41 (3H, s, CH3CCH3), 1.36 (3H, s, CH3CCH3),
0.91 (9H, s, C(CH3)3), 0.10 (3H, s, CH3SiCH3), 0.09 (3H, s,
CH3SiCH3); δC 171.54 (C), 139.80 (CH), 139.34 (C), 109.44
(C), 100.83 (C), 82.29 (CH), 78.96 (CH), 69.06 (CH), 63.75
(CH2), 49.18 (CH3), 49.14 (CH3), 26.72 (CH3), 26.69 (CH3),
25.67 (CH3), 23.95 (CH3), 18.12 (C), Ϫ5.69 (CH3), Ϫ5.74
(CH3); m/z (ES ϩve) 448.0 (M ϩ H, 100%), 416.0 (M Ϫ OCH3,
40) (Found: M ϩ H, 448.218914. C20H38NO6NSSi requires
448.218865).
General procedure for the reduction of ketones 13 and 16
A. With NaBH4. To the stirred solution of the ketone 13 or
16 (0.86 mg, 0.20 mmol) in dry methanol (10 cm3) at Ϫ78 ЊC
was added portionwise solid sodium borohydride (76 mg, 2.0
mmol). After stirring for 6 h, methanol was removed under
reduced pressure and the residue was taken up in water (20 cm3)
and the aqueous layer was extracted with ethyl acetate (20
cm3 × 3). The combined organic extracts were dried over mag-
nesium sulfate and the solvent was removed under reduced
pressure to give a colourless oil. Purification by column
chromatography (50% ethyl acetate–hexane) gave a mixture of
the diastereoisomeric alcohols. The two alcohols were separated
by preparative TLC (75% ethyl acetate–hexane).
B. With DIBAL. To the stirred solution of the ketone 13 or
16 (43 mg, 0.10 mmol) in dry toluene (2 cm3) at Ϫ78 ЊC was
added dropwise a solution of diisobutylaluminium hydride (0.2
mmol). After standing at Ϫ78 ЊC for 24 h, the reaction mixture
was quenched with dry methanol (2 cm3) then diluted with a
saturated solution of ammonium chloride (5 cm3). The aqueous
layer was extracted with ethyl acetate (10 cm3 × 3) and worked
up in similar manner to that described in A.
C. With Red-Al. To the stirred solution of the ketone 13 or 16
(43 mg, 0.10 mmol) in dry toluene (2 cm3) at 0 ЊC was added a
solution of Red-Al (0.50 mmol, 0.16 cm3 of 3.3 M solution
in toluene). The reaction mixture was left to stir at 0 ЊC for
20 min then at room temperature for 10 min. The reaction
was quenched with a saturated solution of sodium chloride
(1 cm3) and the resultant mixture was extracted with ethyl
acetate (10 cm3 × 3) and worked up in similar manner to that
described in A.
D. With L- or K-Selectride. To the stirred solution of the
ketone 13 or 16 (43 mg, 0.10 mmol) in dry tetrahydrofuran (4
cm3) at Ϫ78 ЊC was added a solution of L- or K-Selectride (0.30
mmol, 0.3 cm3 of 1 M solution in tetrahydrofuran). After stir-
ring at Ϫ78 ЊC for 2 h, the reaction mixture was quenched with
a solution of 10% sodium hydroxide (4 cm3) and 30% hydrogen
peroxide (2 cm3). The reaction was stirred at room temperature
for 2 h and was then diluted with a saturated solution of
sodium chloride (2 cm3). The mixture was extracted with ethyl
acetate then worked up in similar manner to that described
in A.
2-(1,1-Dimethoxyethyl)-5-[(1S,2R,3R)-2,3-isopropylidene-
dioxy-1-hydroxy-4-(tert-butyldimethylsilyloxy)butyl]thiazole
14. Mp 48–49 ЊC (Found: C, 53.76; H, 8.44; N, 2.97; S, 7.13.
C20H37NO6SSi requires C, 53.66; H, 8.33; N, 3.13; S, 7.16%);
δH 7.72 (1H, s, 4-H), 5.19 (1H, dd, J 2.7 and 4.5, 1Ј-H), 4.31
(1H, dd, J 2.7 and 6.6, 2Ј-H), 4.24 (1H, ddd, J 3.3, 5.7 and 5.7,
3Ј-H), 3.97 (1H, dd, J 6.3 and 11.4, CHaHb), 3.82 (1H, dd, J 3.6
and 11.1, CHaHb), 3.70 (1H, d, J 5.1, C(1)OH), 3.26 (3H, s,
OCH3), 3.24 (3H, s, OCH3), 1.70 (s, 3H, CH3), 1.57 (3H, s,
CH3CCH3), 1.39 (3H, s, CH3CCH3), 0.90 (9H, s, C(CH3)3), 0.11
(3H, s, CH3SiCH3), 0.10 (3H, s, CH3SiCH3); δC 172.20 (C),
140.20 (CH), 140.01 (C), 108.80 (C), 101.04 (C), 79.99 (CH),
77.05 (CH), 66.36 (CH), 61.28 (CH2), 49.42 (CH3), 49.35
(CH3), 26.74 (CH3), 25.81 (CH3), 24.94 (CH3), 24.17 (CH3),
(1ЈR,2ЈS,3ЈR)-2-Acetyl-5-(1,2,3,4-tetrahydroxybutyl)thiazole 19
To a stirred solution of 17 (0.20 g, 0.44 mmol) in ethanol
(4.5 cm3) was added a solution of 10% hydrochloric acid (2.2
cm3). The reaction was left to stir at room temperature for 2 h.
Ethanol was removed under reduced pressure and the aqueous
layer was washed with diethyl ether. Water was removed under
high vacuum to give 19 as a dark yellow hydroscopic solid
1
(0.116 g, 93%) that was judged to be > 95% purity from H
NMR analysis; [α]D22 Ϫ28.5 (c 1.35, H2O); δH (D2O) 7.84 (1H, s,
4H), 5.07 (1H, d, J 5.4 , 1Ј-H), 3.61 (1H, dd, J 3.0 and 5.1, 2Ј-
H), 3.63–3.64 (3H, m, 3Ј-H and CH2), 2.49 (3H, s, CH3);
δC(D2O) 193.29 (C), 165.85 (C), 148.39 (C), 141.46 (CH2), 73.59
(CH), 71.02 (CH), 67.87 (CH), 62.10 (CH2), 25.28 (CH3); m/z
(ES ϩve) 247.8 (M ϩ H, 90%) (Found: M ϩ H, 248.059270.
C9H14NO5S requires 248.059246).
(1ЈS,2ЈS,3ЈR)-2-Acetyl-5-(1,2,3,4-tetrahydroxybutyl)thiazole 20
The title compound was prepared from 18 (41 mg, 0.09 mmol)
in a similar manner to that described above for the synthesis of
19. Compound 20 was obtained as a dark yellow hydroscopic
J. Chem. Soc., Perkin Trans. 1, 1999, 2281–2291
2287

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solid (24 mg, 94%); [α]D23 18.30 (c 1.2, H2O); δH (D2O) 7.82 (s, 1H,
4-H), 4.92 (1H, d, J 7.8, 1Ј-H), 3.76 (1H, br m, 2Ј-H), 3.56 (1H,
br d, J 8.1, 3Ј-H), 3.48 (2H, m, CH2OH), 2.49 (3H, s, CH3);
δC (D2O) 191.80 (C), 164.81 (C), 148.53 (C), 139.79 (CH), 72.63
(CH), 69.35 (CH), 66.66 (CH), 62.13 (CH2), 25.28 (CH3); m/z
(ES ϩve) 247.8 (M ϩ H, 70%) (Found: M ϩ H, 248.059270.
C9H14NO5S requires 248.059246).
2s, OCH3), 1.71 (3H, s, CH3), 1.38 (3H, s, CH3), 1.28 (3H, s,
CH3), 0.91 (9H, s, tert-butyl), 0.096 (6H, s, 2CH3); δC 171.39
(CH), 140.36 (CH), 140.21 (CH), 109.13 (CH), 101.02 (CH),
81.08 (CH), 77.131 (CH), 69.31 (CH), 66.52 (CH), 64.14
(CH2), 49.42 (CH3), 49.35 (CH3), 28.01 (CH3), 25.82 (CH3),
25.35 (CH3), 24.15 (CH3), 18.27 (C), Ϫ5.40 (CH3), Ϫ5.46
(CH3); m/z (ES ϩve) 478.2294 (M ϩ H, C21H40NO7SSi
requires 478.2294), 446 (100).
2-(1,1-Dimethoxyethyl)-5-[5-O-(tert-butyldimethylsilyl)-2,3-O-
isopropylidene-D-ribofuranosyl]thiazole 22
2-Acetyl-5-[(1R,2R,3R,4R,5)-pentahydroxypentyl]thiazole 25
A solution of n-butyllithium (3.54 cm3, 1.4 M in hexanes, 4.95
mmol) was added with stirring to a cooled (Ϫ78 ЊC) solution of
the thiazole 5 (570 mg, 3.3 mmol) in dry tetrahydrofuran (10
cm3). After stirring for 40 min, a solution of the -ribono-
lactone derivative 21 (995 mg, 3.3 mmol) in dry tetrahydrofuran
(10 cm3) was added dropwise and stirring at Ϫ78 ЊC was con-
tinued for 90 min. The reaction was quenched by pouring into
saturated ammonium chloride solution (50 cm3) and was
extracted with dichloromethane (3 × 50 cm3). The combined
organic extracts were washed with saturated sodium chloride
solution and dried over magnesium sulfate, before concentrat-
ing in vacuo to yield a yellow-brown crystalline compound
(1.892 g, 121%) which was recrystallized from 20% ethyl
acetate–hexane to yield a white crystalline solid (1.001 g, 64%),
mp 147–149 ЊC (Found: C, 52.98; H, 7.89; N, 2.84. C21H37-
NO7SSi requires C, 53.03; H, 7.84; N, 2.94%); δH 7.90 (1H, s,
4-H), 5.65 (1H, s, OH), 4.90 (1H, dd, J 1.5, 5.65, 2Ј-H), 4.59
(1H, d, J 5.65, 3Ј-H), 4.42 (1H, br s, 4Ј-H), 3.84 (2H, m, OCH2),
3.24 (3H, s, OCH3), 3.22 (3H, s, OCH3), 1.75 (3H, s, CH3), 1.50
(3H, s, CH3), 1.25 (3H, s, CH3), 0.98 (9H, s, tert-butyl), 0.19
(3H, s, SiCH3), 0.18 (3H, s, SiCH3); δC (75.6 MHz; CDCl3)
172.6 (C), 141.76 (CH), 137.41 (C), 113.13 (C), 105.21 (C),
101.05 (C), 88.32 (CH), 86.23 (CH), 81.86 (CH), 64.58 (CH2),
49.42 (CH3), 49.37 (CH3), 26.55 (CH3), 25.80 (CH3), 25.07
(CH3), 24.19 (CH3), 18.31 (C), Ϫ5.63 (CH3), Ϫ5.66 (CH3); m/z
(ES ϩve) 476.2138 (M ϩ H; C21H38NO7SSi requires 476.2138),
444 (100%).
Compound 23 (200 mg, 0.42 mmol) was refluxed in a 50:50
mixture of acetone and 10% hydrochloric acid solution for 2 h.
Upon completion, the acetone was removed in vacuo and the
remaining aqueous solution was washed with diethyl ether. The
water was removed in vacuo, leaving the crude product as a
1
dark yellow oil (106 mg, 91%). H NMR analysis showed this
product to be >95% pure. δH (D2O) 7.77 (1H, s, 4-H), 5.22 (1H,
s, 1Ј-H), 3.73 (1H, dd, J 3.3, 7.2), 3.67 (1H, dd, J 4.4, 8.4), 3.56
(2H, m), 3.45 (1H, dd, J 7.5, 12); δC (D2O) 212.1 (C), 183.9 (C),
167.4 (C), 159.3, 92.3 (CH), 90.9 (CH), 89.5 (CH), 85 (CH),
80.1 (CH2), 43.8 (CH3); m/z (ES ϩve) 300 (M ϩ Na, 100%), 278
(M ϩ H, 100%), 260 (M ϩ H Ϫ H2O, 35%).
2-Acetyl-5-[(1S,2R,3R,4R,5)-pentahydroxypentyl]thiazole 26
Compound 24 (200 mg, 0.42 mmol) was hydrolysed as
described above for the preparation of compound 25 from 23.
The product was obtained as a dark yellow oil (103 mg, 89%).
1H NMR analysis showed this product to be >95% pure. δH
(D2O) 7.77 (1H, s, 4-H), 5.1 (1H, d, J 3.93, 1Ј-H), 3.78 (1H, dd,
J 4.05, 8.10), 3.61 (1H, m), 3.51 (1H, dd, J 2.47, 11.92), 3.37
(1H, dd, J 7.42, 11.92), 3.14 (1H, dd, J 4.50, 8.10); δC (D2O)
212.1 (C), 184.7 (C), 164.4 (C), 160.6 (C), 91.7 (CH), 90.7
(CH), 90.1 (CH), 86.3 (CH), 80.1 (CH2), 43.8 (CH3); m/z (ES
ϩve) 300 (M ϩ Na, 20%), 278 (M ϩ H, 60%), 260 (M ϩ H Ϫ
H2O, 3%).
2-Acetyl-5-[(1R,2R,3R,4R,5)-pentaacetylpentyl]thiazole 27
2-(1,1-Dimethoxyethyl)-5-(1,4-dihydroxy-2,3-isopropylidene-
To a stirred solution of acetic anhydride (3 cm3) and glacial
acetic acid (5 cm3) was added a sample of 25 (100 mg, 0.36
mmol). A perchloric acid–acetic anhydride catalyst (1 g of 70%
hydrochloric acid in 2.3 g acetic anhydride) was added (4 drops)
and the mixture was stirred at 60 ЊC for 1 h before being poured
into ice–water (20 cm3). After extraction with ethyl acetate
(3 × 20 cm3) the combined organic extracts were dried over
magnesium sulfate and concentrated in vacuo. The product
was purified by semi-prep. TLC on silica plates (eluent 50%
ethyl acetate–hexane) to yield a pale yellow oil (110 mg, 63%);
δH 7.94 (1H, s, 4-H), 6.40 (1H, d, J 3.69, 1Ј-H), 5.44 (1H, dd,
J 3.69, 7.60, 2Ј-H), 5.33 (1H, dd, J 3.96, 7.60, 3Ј-H), 5.22 (1H,
m, J 3.3, 11.02, 4Ј-H), 4.33 (1H, dd, J 3.3, 12.08, 5Ј-Ha), 4.17
(1H, dd, J 7.66, 12.08, 5Ј-Hb), 2.68 (3H, s, CH3), 2.16 (3H, s,
Ac), 2.10 (3H, s, Ac), 2.094 (3H, s, Ac), 2.090 (3H, s, Ac), 2.04
(3H, s, Ac); m/z (CI ϩve) 488.1226 (M ϩ H, C20H26NO11S
requires 488.1226) 428 (65%), 386 (77).
dioxy-5-tert-butyldimethylsilyloxypentyl)thiazole 23 and 24
Sodium borohydride (596 mg, 15.7 mmol) was added to a
stirred solution of the lactol 22 (1 g, 2.1 mmol) in dry
methanol (50 cm3) at 0 ЊC over a period of 1 h. The reaction
was left for 3 h at 0 ЊC before quenching with saturated
ammonium chloride solution (50 cm3). Extraction with di-
chloromethane (3 × 50 cm3) yielded an organic fraction which
was washed with saturated sodium chloride solution and dried
over magnesium sulfate before concentrating in vacuo. The
crystalline crude product (961 mg, 96%) was purified by column
chromatography using silica gel (1:1 ethyl acetate–hexane) to
yield 23 (461 mg, 48%) as a fine powdery solid and 24 (442 mg,
46%) as a crystalline solid.
23: mp 150–153 ЊC; δH 7.69 (1H, s, 4-H), 5.39 (1H, dd, J 1.77,
7.47, 1Ј-H), 4.35 (1H, dd, J 2.08, 6.23, 2Ј-H), 4.11 (1H, dd,
J 6.23, 9.34, 3Ј-H), 4.03 (1H, m, 4Ј-H), 3.79 (1H, dd, J 3.14,
10.10, 5Ј-Ha), 3.65 (1H, dd, J 4.91, 10.10, 5Ј-Hb), 3.27 (1H, d,
J 7.47, 1Ј-OH), 3.22 (6H, 2s, OCH3), 2.9 (1H, d, J 5.65, 4Ј-OH),
1.68 (3H, s, CH3), 1.5 (3H, s, CH3), 1.32 (3H, s, CH3), 0.9 (9H, s,
tert-butyl), 0.09 (6H, s, 2CH3); δC 172.03 (C), 140.86 (C), 140.12
(CH), 108.906 (C), 100.98 (C), 79.61 (CH), 76.19 (CH), 69.285
(CH), 65.99 (CH), 64.24 (CH2), 49.36 (CH3), 49.34 (CH3), 26.72
(CH3), 25.78 (CH3), 24.61 (CH3), 24.12 (CH3), 18.24 (C), Ϫ5.42
(CH3), Ϫ5.54 (CH3); m/z (ES ϩve) 478.2294 (M ϩ H, C21H40-
NO7SSi requires 478.2294), 446 (100).
2-Acetyl-5-[(1S,2R,3R,4R,5)-pentaacetylpentyl]thiazole 28
The title compound was prepared from 26 (100 mg, 0.36 mmol)
as described above for the synthesis of 27 from 25. The product
was purified by semi-prep. TLC on silica plates (eluent 50%
ethyl acetate–hexane) to yield a pale yellow oil (101 mg, 58%);
δH 7.9 (1H, s, 4-H), 6.25 (1H, d, J 4.63, 1Ј-H), 5.57 (1H, dd,
J 4.63, 6.24, 2Ј-H), 5.24 (1H, m, 3.26, 6.65, 4Ј-H), 5.18 (1H, dd,
J 5.15, 6.24, 3Ј-H), 4.30 (1H, dd, J 3.26, 12.18, 5Ј-Ha), 4.1 (1H,
dd, J 6.65, 12.18, 5Ј-Hb), 2.69 (3H, s, CH3), 2.16 (3H, s, Ac),
2.09 (3H, s, Ac), 2.07 (3H, s, Ac), 2.03 (3H, s, Ac), 2.01 (3H, s,
Ac); m/z (CI ϩve) 488.1226 (M ϩ H, C20H26NO11S requires
488.1226), 428 (65%), 386 (37).
24: mp 88–89 ЊC; δH 7.78 (1H, d, J 0.7, 4-H), 5.13 (1H, dd,
J 3.04, 9.14, 1Ј-H), 4.91 (1H, d, J 3.04, 1Ј-OH), 4.27 (1H, dd,
J 5.33, 9.45, 2Ј-H), 4.13 (1H, dd, J 5.33, 9.45, 3Ј-H), 3.91
(1H, m, 5Ј-Ha), 3.87 (1H, m, J 3.3, 4Ј-H), 3.66 (1H, dd,
J 8.11, 10.81, 5Ј-Hb), 3.39 (1H, d, J 3.3, 4Ј-OH), 3.24 (6H,
2288
J. Chem. Soc., Perkin Trans. 1, 1999, 2281–2291

View Article Online
2-(1,1-Dimethoxyethyl)-4-[5-O-(tert-butyldimethylsilyl)-2,3-O-
isopropylidene-D-ribofuranosyl]thiazole 29
(CH2), 49.40 (CH3), 49.36 (CH3), 27.26 (CH3), 25.86 (CH3),
24.89 (CH3), 24.31 (CH3), 18.31 (C), Ϫ5.37 (CH3), Ϫ5.44
(CH3); m/z (CI ϩve) 478.2294 (M ϩ H, C21H40NO7SSi requires
478.2294).
4-Bromo-2-(1,1-dimethoxyethyl)thiazole6 (520 mg, 2.06 mmol)
was dissolved in anhydrous diethyl ether (10 cm3) and cooled to
Ϫ78 ЊC before addition of n-butyllithium (2.2 cm3, 1.4 M solu-
tion in hexanes, 3.1 mmol). After stirring at Ϫ78 ЊC for 30 min,
a solution of the -ribonolactone derivative 21 (623 mg, 2.06
mmol) in dry diethyl ether (5 cm3) was added dropwise. The
reaction was left stirring at Ϫ78 ЊC for 90 min, before pouring
into saturated ammonium chloride solution (15 cm3) and
extracting the aqueous layer with dichloromethane (3 × 25
cm3). The combined organic layers were washed with saturated
sodium chloride solution before drying over magnesium sulfate
and concentrating in vacuo to yield a yellow oil (1083 mg,
110%). Purification on a silica gel column (eluent 30% ethyl
acetate–hexane) gave two major products. The title compound
was isolated (433 mg, 44%) and 1H NMR analysis showed this
to be a 69:31 mixture of isomers which was used as such for the
following reaction. Also isolated was the addition product in
the C5 thiazole position as a crystalline solid (142 mg, 14.5%).
29 (Minor isomer): δH 7.47 (1H, s, 5-H), 5.26 (1H, s, OH),
4.98 (1H, d, J 6.82, 2Ј-H), 4.85 (1H, dd, J 3.24, 6.82, 3Ј-H), 4.27
(1H, ddd, J 3.24, 4.16, 5.17, 4Ј-H), 3.77 (1H, dd, J 5.17, 10.97,
5Ј-Hb), 3.71 (1H, dd, J 4.16, 10.97, 5Ј-Ha), 3.23 (3H, s, OCH3),
3.18 (3H, s, OCH3), 1.68 (3H, s, CH3), 1.62 (3H, s, CH3), 1.39
(3H, s, CH3), 0.83 (9H, s,tert-butyl), 0.01 (3H, s, SiCH3), Ϫ0.01
(3H, s, SiCH3).
2-Acetyl-4-[(1R,2R,3R,4R,5)-pentahydroxypentyl]thiazole 32
Compound 30 (97 mg, 0.203 mmol) was refluxed in a 50:50
mixture (10 cm3) of acetone and 10% hydrochloric acid solution
for 2 h. Upon completion, the acetone was removed in vacuo
and the remaining aqueous solution washed with diethyl ether.
The water was removed in vacuo, leaving the crude product as a
1
dark yellow oil (49 mg, 87%). H NMR analysis showed this
product to be >95% pure. δH (D2O) 7.27 (1H, s, 4-H), 5.05 (1H,
d, 1Ј-H), 3.4–3.95 (5H, series of m, 2Ј-H to 6Ј-H), 2.53 (3H, s,
CH3); m/z (ES ϩve) 300 (M ϩ Na, 100%), 278 (M ϩ H, 22%),
260 (M ϩ H Ϫ H2O, 21%).
2-Acetyl-4-[(1S,2R,3R,4R,5)-pentahydroxypentyl]thiazole 33
Compound 31 (60 mg, 0.125 mmol) was treated as described
above for the preparation of 32 from 30 to yield the title com-
1
pound as a dark yellow oil (30 mg, 86%). H NMR analysis
showed this compound to be >95% pure. δH (D2O) 7.74 (1H,
s, 4Ј-H), 5.08 (1H, d, J 2.29, 1Ј-H), 3.87 (1H, dd, J 2.32, 7.78,
2Ј-H), 3.80–3.67 (2H, m, 3Ј-H, 4Ј-H), 3.65 (1H, dd, J 2.84,
11.86, 5Ј-Ha), 3.52 (1H, dd, J 7.02, 11.86, 5Ј-Hb), 2.54 (3H, s,
CH3); m/z (ES ϩve) 278 (M ϩ H, 25%), 260 (M ϩ H Ϫ H2O,
98%).
29 (Major isomer): δH 7.46 (1H, s, 5-H), 4.86 (1H, dd, J 1.33,
5.78, 3Ј-H), 4.75 (1H, d, J 5.78, 2Ј-H), 4.53 (1H, s, OH), 4.38
(1H, ddd, J 1.33, 3.51, 4.65, 4Ј-H), 3.86 (1H, dd, J 4.65, 10.82,
5Ј-Hb), 3.79 (1H, dd, J 3.51, 10.82, 5Ј-Ha), 3.21 (3H, s, OCH3),
3.18 (3H, s, OCH3), 1.72 (3H, s, CH3), 1.34 (3H, s, CH3), 1.24
(3H, s, CH3), 0.91 (9H, s, tert-butyl), 0.11 (3H, s, SiCH3), 0.10
(3H, s, SiCH3).
2-Acetyl-4-[(1R,2R,3R,4R,5)-pentaacetylpentyl]thiazole 34
To a stirred solution of acetic anhydride (3 cm3) and glacial
acetic acid (5 cm3) was added a sample of 32 (10 mg, 0.036
mmol). A perchloric acid–acetic anhydride catalyst (1 g of 70%
HClO4 in 2.3 g acetic anhydride) was added (4 drops) and the
mixture was stirred at 60 ЊC for 1 h before being poured into
ice–water (20 cm3). After extraction with ethyl acetate (3 × 20
cm3) the combined organic extracts were dried over magnesium
sulfate and concentrated in vacuo. The product was purified by
semi-prep. TLC on silica gel plates (eluent 50% ethyl acetate–
hexane) to yield a finely crystalline product (11 mg, 63%).
δH 7.53 (1H, s, 4-H), 6.24 (1H, d, J 4.06, 1Ј-H), 5.70 (1H, dd,
J 4.06, 7.69, 2Ј-H), 5.35 (1H, dd, J 3.7, 7.69, 3Ј-H), 5.21 (1H, m,
J 3.35, 7.43, 11.00, 4Ј-H), 4.37 (1H, dd, J 3.35, 12.07, 5Ј-Ha),
4.15 (1H, dd, J 7.43, 12.07, 5Ј-Hb), 2.68 (3H, s, CH3), 2.15 (3H,
s, Ac), 2.094 (3H, s, Ac), 2.073 (3H, s, Ac), 2.058 (3H, s, Ac),
2.029 (3H, s, Ac); m/z (CI ϩve) 488.122658 (M ϩ H, C20H26-
NO11S requires 488.122658).
2-(1,1-Dimethoxyethyl)-4-(1,4-dihydroxy-2,3-isopropylidene-
dioxy-5-tert-butyldimethylsiloxypentyl)thiazole 30 and 31
Sodium borohydride (32 mg, 0.85 mmol) was added to a
cooled, stirred solution of the lactol 29 (269 mg, 0.56 mmol) in
dry methanol (5 cm3) over a period of 1 h. The solution was
stirred for 3 h, then quenched with saturated ammonium
chloride solution and extracted with dichloromethane. The
combined organic fractions were washed with saturated sodium
chloride solution and dried over magnesium sulfate. Concen-
tration in vacuo yielded the crude product as a mixture of
isomers, in a 41:59 ratio (31:30) with an overall yield of 65%.
Purification on a silica column (eluent 25% ethyl acetate–
hexane) gave 30 as an orange oil (81 mg, 30%) and 31 as a white
crystalline solid (56 mg, 21%).
2-Acetyl-4-[(1S,2R,3R,4R,5)-pentaacetylpentyl]thiazole 35
30: δH 7.26 (1H, s, 4-H), 5.07 (1H, dd, J 4.07, 9.2, 1Ј-H), 4.69
(1H, d, J 4.07, 1Ј-OH), 4.53 (1H, dd, J 5.19, 9.2, 2Ј-H), 4.21
(1H, dd, J 5.19, 9.51, 3Ј-H), 3.98 (1H, m, 4Ј-H), 3.92 (1H, dd,
J 2.88, 10.01, 5Ј-Ha), 3.73 (1H, dd, J 6.25, 10.01, 5Ј-Hb), 3.68
(1H, d, J 3.64, C(5)OH), 3.25 (6H, 2s, 2(OCH3)), 1.71 (3H, s,
CH3), 1.36 (3H, s, CH3), 1.26 (3H, s, CH3), 0.9 (9H, s, tert-
butyl), 0.09 (6H, s, 2CH3); δC 171.28 (C), 156.23 (C), 116.78
(CH), 108.65 (C), 100.91 (C), 79.91 (CH), 77.06 (CH), 69.48
(CH), 68.08 (CH), 64.44 (CH2), 49.33 (CH3), 27.99 (CH3),
25.86 (CH3), 25.42 (CH3), 24.2 (CH3), 18.325 (C), Ϫ5.38 (CH3);
m/z (ES ϩve) 478.2294 (M ϩ H, C21H40NO7SSi requires
478.2294).
31: δH 7.31 (1H, s, 4-H), 5.33 (1H, dd, J 2.7, 6.5, 1Ј-H), 4.67
(1H, dd, J 2.9, 5.9, 2Ј-H), 4.14 (1H, dd, J 5.93, 9.38, 3Ј-H), 4.08
(1H, m, 4Ј-H), 3.85 (1H, dd, J 3.1, 10.15, 5Ј-Ha), 3.71 (1H, dd,
J 5.1, 10.15, 5Ј-Hb), 3.41 (1H, d, J 6.7, 1Ј-OH), 3.21 (6H, 2s,
2(OCH3)), 3.20 (1H, d, J 5.4, 4Ј-OH), 1.69 (3H, s, CH3), 1.45
(3H, s, CH3), 1.29 (3H, s, CH3), 0.88 (9H, s, tert-butyl), 0.07
(6H, s, 2CH3); δC 171.63 (C), 157.72 (C), 115.64 (CH), 108.32
(C), 100.89 (C), 78.92 (CH), 76.39 (CH), 69.24 (CH), 64.38
Compound 33 (30 mg, 0.108 mmol) was treated as described
above for the preparation of 34 from 32 to yield a finely crystal-
line product (30 mg, 57%). δH 7.59 (1H, s, 4-H), 6.18 (1H, d,
J 5.51, 1Ј-H), 5.75 (1H, dd, J 5.51, 5.87, 2Ј-H), 5.40 (1H, dd,
J 4.34, 5.87, 3Ј-H), 5.29 (1H, m, J 3.03, 7.10, 4Ј-H), 4.35 (1H,
dd, J 3.03, 12.10, 5Ј-Ha), 4.07 (1H, dd, J 7.10, 12.10, 5Ј-Hb),
2.63 (3H, s, CH3), 2.18 (3H, s, Ac), 2.049 (3H, s, Ac), 2.009
(3H, s, Ac), 2.001 (3H, s, Ac), 1.978 (3H, s, Ac); m/z (CIϩ)
488.122658 (M ϩ H, C20H26NO11S requires 488.122658).
Structure determinations†
Diffraction data were acquired in a number of modes, at the
specified temperature, all instruments equipped with mono-
chromatic Mo-Kα radiation, λ = 0.71073 Å. Using a single
counter instrument in 2θ/θ scan mode, N unique reflections
were measured within the specified 2θmax limit, No with I > 3σ(I)
being considered ‘observed’, gaussian absorption corrections
† CCDC reference number 207/345.
J. Chem. Soc., Perkin Trans. 1, 1999, 2281–2291
2289

View Article Online
being applied. Data were also measured using a Bruker AXS
CCD instrument (2θmax = 58Њ), Ntot(al) reflections within a
full sphere being merged to N unique, Rint as specified after
‘empirical’/multiscan absorption correction within the
proprietary/preprocessing software SMART/SAINT; the
‘observed’ criterion, where applicable, was F > 4σ(F ). Aniso-
tropic thermal parameter forms were refined in a full matrix
context for non-hydrogen atoms, (x, y, z, Uiso)H being con-
strained at estimated values. Conventional residuals R, Rw
(statistical weights) on |F | are quoted at convergence. Neutral
atom complex scattering factors were employed within the Xtal
3.4 program system.16 Pertinent results are given in the Figures
and below; individual variations in procedure/difficulties/
idiosyncrasies are cited as ‘variata’. Molecular projections as
shown in Figs. 1–9 are projected normal to the common hetero-
cyclic ring, which, together with the second common ring and
linkages, is shown with solid bonds; additional projections are
offered to clarify the appendages where appropriate. A common
ad hoc crystallographic numbering is shown, carbon atoms
denoted by number only. Non-hydrogen atoms are shown with
20 (room-temperature) or 50% (low temperature) probability
displacement ellipsoids. Bond lengths and angles are generally
as expected throughout the array and are not addressed further,
the interest lying in the isomeric and conformational variation
discussed in the text above and shown in the Figures.
17. C20H36NO6SSi, M = 446.7. Single-counter instrument, T
ca. 295 K. Orthorhombic, space group P212121, a = 30.699(5),
b = 10.843(1), c = 7.615(2) Å, V = 2535 Å3. Dc (Z = 4) = 1.171 g
cmϪ3; F(000) = 964. µMo = 2.1 cmϪ1; specimen: 0.70 × 0.40 ×
0.85 mm; ‘T’min, max = 0.91, 0.95. 2θmax = 50Њ; Ntot = 8012, N =
2565 (Rint = 0.025), No = 2007; R = 0.056, Rw = 0.072; nν = 263,
|∆ρmax| = 0.73 e ÅϪ3
.
Variata. Chirality was assigned from the chemistry. The
hydroxy hydrogen atom was not located.
22. C21H37NO7SSi, M = 475.7. Area-detector instrument, T
ca. 153 K. Orthorhombic, space group P212121, a = 6.9634(5),
b = 10.0227(8), c = 36.608(3) Å, V = 2555 Å3. Dc (Z = 4) = 1.236
g cmϪ3; F(000) = 1024. µMo = 2.1 cmϪ1; specimen: 0.70 × 0.22 ×
0.11 mm; ‘T ’min, max = 0.83, 0.97. Ntot = 27955, N = 3759 (Rint
0.024), No = 3677; R = 0.038, Rw = 0.074.
=
Variata. (x, y, z, Uiso)H were refined. Friedel data were pre-
served distinct, the absolute structure parameter xabs refining
to Ϫ0.02(18). Hydroxyl OH(51) is hydrogen-bonded to N(3)
of an adjacent molecule (¹ ϩ x, 1¹ Ϫ y, z¯) (O,H ؒ ؒ ؒ N 2.817(6),
¯
²
¯
²
2.13(8) Å).
24. C21H39NO7SSi, M = 477.7. Area-detector instrument, T
ca. 153 K. Orthorhombic, space group P212121, a = 5.8742(4),
b = 16.675(1), c = 26.302(2) Å, V = 2576 Å3. Dc (Z = 4) = 1.232 g
cmϪ3; F(000) = 1032. µMo = 2.1 cmϪ1; specimen: 0.40 × 0.10 ×
Crystal/refinement data
0.10 mm; ‘T’min, max = 0.68, 0.96. Ntot = 28121, N = 3737 (Rint
0.041), No = 3120; R = 0.040, Rw = 0.026; nν = 452, |∆ρmax| = 0.39
e ÅϪ3
=
7b. C14H21NO6S, M = 331.4. Single-counter instrument, T ca.
295 K. Orthorhombic, space group P212121 (D24, No. 19), a =
23.949(6), b = 11.294(2), c = 6.166(1) Å, V = 1668 Å3. Dc
(Z = 4) = 1.320 g cmϪ3; F(000) = 704. µMo = 2.2 cmϪ1; specimen:
0.38 × 0.36 × 0.15 mm; ‘T’min, max = 0.94, 0.95. 2θmax = 50Њ; Ntot
(hemisphere) = 6203, N = 1726 (Rint = 0.028), No = 1431; R =
.
Variata. Methyl 24 was disordered (site occupancies set at 0.5
after trial refinement) with one of the associated methoxy
groups. (x, y, z, Uiso) were refined for all fully weighted hydrogen
atoms. O(51,57) are in close proximity (O ؒ ؒ ؒ O 2.800(3) Å),
with the OH(57) hydrogen hydrogen-bonded to O(51) (H ؒ ؒ ؒ O
2.14(3) Å). OH(51) is hydrogen-bonded to N(3) of an adjacent
molecule (OH ؒ ؒ ؒ N (¹ ϩ x, ¹ Ϫ y, 2 Ϫ z) 2.792(4), 2.00(3) Å).
0.039, Rw = 0.042; nν = 217, |∆ρmax| = 0.21 e ÅϪ3
.
Variata. At C(21), one of the pendant methyl groups was
disordered with the methoxy group; site occupancies of both
were set at 0.5 after trial refinement (C, O isotropic thermal
parameter forms). The (OH(51)) hydroxy hydrogen atom was
observed in difference maps, and appears to be hydrogen-
bonded to N(3) of an adjacent molecule. (O,H ؒ ؒ ؒ N (¹ Ϫ x,
¯
²
¯
²
27. C20H25NO11S, M = 487.5. Area-detector instrument, T ca.
153 K. Monoclinic, space group P21, a = 9.820(1), b = 8.170(1),
c = 14.692(2) Å, β = 99.986(2)Њ, V = 1161 Å3. Dc (Z = 2) = 1.394
g cmϪ3; F(000) = 512. µMo = 2.0 cmϪ1; specimen: 0.60 × 0.13 ×
¯
²
1 Ϫ y, z Ϫ ¹) 2.828(4), 1.9 Å). Chirality was assigned from the
chemistry.
¯
²
0.10 mm; ‘T ’min, max = 0.77, 0.96. Ntot = 13077, N = 3123 (Rint
0.027), No = 2610; R = 0.040, Rw = 0.041; nν 399, |∆ρmax| = 0.33
e ÅϪ3
=
.
9. C14H23NO6S, M = 333.4. Single-counter instrument, T ca.
295 K. Monoclinic, space group P21 (C22, No. 4), a = 6.644(1),
b = 18.553(3), c = 13.507(2) Å, β = 97.31(1)Њ, V = 1651 Å3. Dc
(Z = 4) = 1.341 g cmϪ3; F(000) = 712. µMo = 2.2 cmϪ1; specimen:
0.68 × 0.23 × 0.70 mm; ‘T’min, max = 0.91, 0.95. 2θmax = 50Њ; Ntot
(hemisphere) = 4248, N = 2289 (Rint = 0.019); R = 0.044, Rw =
Variata. (x, y, z, Uiso)H (all H) were refined.
30ؒH2O. C21H41NO8SSi, M = 495.7. Area-detector instru-
ment, T ca. 300 K. Orthorhombic, space group P212121,
a = 7.3320(6), b = 15.956(1), c = 24.333(2) Å, V = 2847 Å3. Dc
(Z = 4) = 1.156 g cmϪ3; F(000) = 1072. µMo = 2.0 cmϪ1; specimen:
0.55 × 0.45 × 0.40 mm; ‘T ’min, max = 0.76, 0.94. Ntot = 20618,
N = 3235 (Rint = 0.021), No = 2341; R = 0.043, Rw = 0.041;
0.079 (refinement on F2 (all data)); nν = 406, |∆ρmax| = 0.34 e ÅϪ3
.
Variata. All hydrogen atoms were observed in difference
maps; hydroxy OH(258) was disordered over a pair of sites,
occupancy set at 0.5 each after trial refinement. Chirality was
assigned from the chemistry. In molecule 1, OH(151) is intra-
molecularly hydrogen-bonded to O(158) (O,H ؒ ؒ ؒ O 2.712(5),
1.8 Å); other putative hydrogen-bonds are weaker with distances
between the parent atoms greater than 2.8 Å.
nν = 319, |∆ρmax| = 0.25 e ÅϪ3
.
Variata. Methyl 24/methoxy 23 were modelled as disordered
between both sets of sites, occupancies 0.42(2) and comple-
ment. Hydroxylic atoms were located in difference maps.
Friedel data were preserved distinct with the absolute structure
parameter xabs refining to 0.02(15). Hydroxy OH(51) is
hydrogen-bonded to the water molecule (O,H ؒ ؒ ؒ O (x Ϫ 1, y, z)
2.703(4), 1.8 Å) while hydroxy O(58) is hydrogen-bonded to
O(51) of an adjoining molecule (O,H ؒ ؒ ؒ O (¹ ϩ x, 1¹ Ϫ y,
10. C14H23NO6S, M = 333.4. Single-counter instrument, T ca.
295 K. Tetragonal, space group P41 (C42, No. 76), a = 9.330(3),
c = 19.648(8) Å, V = 1710 Å3. Dc (Z = 4) = 1.295 g cmϪ3
;
¯
²
¯
²
F(000) = 712. µMo = 2.2 cmϪ1; specimen: 0.43 × 0.37 × 0.40 mm;
‘T’min, max = 0.92, 0.94. 2θmax = 48Њ; Ntot = 4966, N = 1378 (Rint
0.042) (refinement on F2 (all data)); R = 0.038, Rw = 0.059;
nν = 291, |∆ρmax| = 0.17 e ÅϪ3
1 Ϫ z) 2.707(4), 1.8 Å). One of the water molecule hydrogen
atoms is hydrogen-bonded to the nitrogen atom (O,H(b) ؒ ؒ ؒ N
2.928(5), 2.0 Å).
=
.
Variata. (x, y, z, Uiso)H were refined throughout; chirality was
assigned from the chemistry. OH(51) is intramolecularly
hydrogen-bonded to O(58) (O,H ؒ ؒ ؒ O 2.719(6), 1.96(5) Å), with
OH(58) intermolecularly hydrogen-bonded to N(3) of an
adjoining molecule (O,H ؒ ؒ ؒ N (x Ϫ 1, y, z) 2.840(5), 2.09(7) Å).
Acknowledgements
We thank Johnson and Johnson Research Pty. Limited
(Sydney) for supporting this project and the Australian
Research Council for an APA(I) scholarship to GRJ.
2290
J. Chem. Soc., Perkin Trans. 1, 1999, 2281–2291

View Article Online
11 N. T. Anh, Top. Curr. Chem., 1980, 88, 145.
12 H. Chikashita, T. Nikaya, H. Uemura and K. Itoh, Bull. Chem. Soc.
Jpn., 1989, 62, 2121.
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