Stereoselective synthesis of α-O-fucosylated serine, threonine, tyrosine and saccharides

Article abstract of DOI:10.1039/a704310d

Stereoselectiye fucosylation of Boc-Ser/Thr/Tyr-OMe 2-4 and several saccharide alcohols 5-7 by coupling with 2-pyridyl tri-O-benzyl-1-thio-β-L-fucosyl donor 1b under iodomethane activation procedure results in the formation of α-linked fucosylated amino a

Full text of DOI:10.1039/a704310d

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Stereoselective synthesis of á-O-fucosylated serine, threonine,
tyrosine and saccharides
Hari Babu Mereyala,* Srinivas Reddy Gurrala and
Rajendrakumar Reddy Gadikota
Organic Division III, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Stereoselective fucosylation of Boc-Ser/Thr/Tyr-OMe 2–4 and several saccharide alcohols 5–7 by
coupling with 2-pyridyl tri-O-benzyl-1-thio-â-L-fucosyl donor 1b under iodomethane activation procedure
results in the formation of á-linked fucosylated amino acid methyl ester building blocks 8–10 and á-linked
fucosyl saccharides 11–13, respectively.
by the appearance of the anomeric proton signal at δ 5.8 (d, J1,2
Introduction
10 Hz) and aromatic protons (4 H) between δ 6.90–8.50. Com-
pound 1a on further reaction with a catalytic amount of
sodium methoxide in methanol for 6 h at room temp. resulted in
the formation of 2-pyridyl 1-thio-β--fucopyranoside (l; R = H)
which was allowed to react with NaH–benzyl bromide (BnBr)–
dimethylformamide (DMF) at 0 ЊC for 3 h to obtain 2-pyridyl
2,3,4-tri-O-benzyl-1-thio-β--fucopyranoside 1b as a crystalline
solid, mp 134–136 ЊC, in 76% yield. Fucosylation of N-Boc-
serine methyl ester 2‡ was carried out by reaction with com-
pound 1b in the presence of iodomethane as activator in
dichloromethane at 50 ЊC for 62 h to afford, in high stereo-
control, the α-linked N-Boc-3-O-(2,3,4-tri-O-benzyl-α--fuco-
pyranosyl)--serine methyl ester 8 in 79% yield, as a syrup, [α]D
Ϫ31 (c 1.0, CHCl3). The presence of an α-glycosidic linkage in
compound 8 was confirmed by the small coupling constant J1Ј,2Ј
A large number of proteins found in nature are N- and/or
O-glycosylated, and the structural diversity of the oligo-
saccharides and the variety of linkages between sugar and
protein moieties is enormous.1,2 Glycosylation of a protein is
known to influence the properties of the protein in many ways.2
Glycosylation provides protection against proteolysis, influ-
ences uptake of serum proteins of the liver, effects intra-
molecular transport of enzymes to lysosomes, determines
human blood groups and regulates leukocyte trafficking to sites
of inflammation.3,4 Tumour cells show aberrant glycosylation
of glycosphingolipids and glycoproteins.5 A novel type of O-
glycosylation where Xyl-Glc and Xyl-Xyl-Glc have been found
attached to serine residues has been reported by several authors
investigating the N-terminal Epidermal Growth Factor (EGF).6
More recently, -fucose has been found α-glycosidically linked
to serine or threonine residues within the peptide motif Cys-X-
X-Gly-Gly-Thr/Ser-Cys.6 Harris et al. have identified the
tetrasaccharide NeuAcα(2→6)Galβ(1→4)GlcNAcβ(1→3)Fucα
1→O-linked to serine 61 of Human Factor IX.7 Furthermore,
-fucose is known to be an important residue of branched
oligosaccharides in glycoconjugates that bind to selectins.8
These interesting biological properties have led to the synthesis
of fucosylated peptides9 and saccharides10 by both enzymic11
and chemical methods12 by organic chemists in order to facili-
tate study of the biological functions of peptides which are not
glycosylated in nature. Synthetic fucosylated glycopeptides
might be potential mimetics of selectin-binding oligosacchar-
ides. Chemical synthesis of building blocks required for glyco-
peptide9,12 and fucosyl saccharide synthesis10 has been achieved
by use of fluoro, chloro, bromo, acetoxy, acetamidate and
alkylthio fucosyl donors.9,10 Proven success13,14 in recent years
in the development of the iodomethane activation procedure
of 2-pyridylthio glycosides for the stereoselective synthesis
of α-linked saccharides has prompted us to look into its
applicability for the synthesis of α-fucosylated amino acids and
saccharides.
1
3.8 Hz in the H NMR spectrum and from the appearance of
C-1Ј at δC 94.53 in the 13C NMR spectrum. Likewise, N-Boc-
threonine methyl ester 3 and N-Boc-tyrosine methyl ester 4
were treated with compound 1b to obtain N-Boc-3-O-(2,3,4-
tri-O-benzyl-α--fucopyranosyl)--threonine methyl ester 9 and
N-Boc-3-O-(2,3,4-tri-O-benzyl-α--fucopranosyl)--tyrosine
methyl ester 10, respectively, in good yields (73–76%) and which
were characterised by their respective 1H and 13C NMR spectra.
Coupling of the glycosyl acceptors 1,2:3,4-di-O-isopropyl-
idene-α--galactopyranoside 5, 1,2:5,6-di-O-isopropylidene-α-
-glucofuranose 6 and benzyl 2-acetamido-4,6-O-benzylidene-
2-deoxy-α--glucopyranose 7 with the 2-pyridylthio donor 1b
in dichloromethane containing iodomethane at 50 ЊC for 48–
64 h gave their respective α-linked disaccharides 1,2:3,4-di-O-
isopropylidene-6-O-(2,3,4-tri-O-benzyl-α--fucopyranosyl)-α-
-galactopyranose 11 as a crystalline solid, mp 115–116 ЊC
(lit.,10 116–117 ЊC), [α]D Ϫ118 (c 2.0, CH2Cl2) {lit.,10 [α]D Ϫ117
(c 2.0, CH2Cl2)}, 1,2:5,6-di-O-isopropylidene-3-O-(2,3,4-tri-O-
benzyl-α--fucopyranosyl)-α--glucofuranose 12 as a syrup,
characterised by comparison of the spectral data with those
reported in the literature,10 and benzyl 2-acetamido-4,6-
O-benzylidene-2-deoxy-3-O-(2,3,4-tri-O-benzyl-α--fucopyran-
osyl)-α--glucopyranoside 13 as a crystalline compound (mp
1
183 ЊC), characterised from the H NMR spectral data: ap-
Results and discussion
pearance of 1Ј-H signal at δ 5.21 as a doublet with a small
coupling J1Ј,2Ј of 3.5 Hz, and from the 13C NMR spectrum:
appearance of C-1,1Ј signals at δC 97.2 and 99.4.
In conclusion, yet another highly stereoselective α-fuco-
sylation of amino acid esters and several sugar alcohols has
been achieved by iodomethane activation of perbenzylated 2-
pyridyl thio--fucosyl donors.
2,3,4-Tri-O-acetyl-α--fucopyranosyl bromide15 was treated
with 2-mercaptopyridine and K2CO3 in acetone–toluene (3:2)
at room temperature for 4 h to obtain 2-pyridyl 2,3,4-tri-O-
acetyl-1-thio-β--fucopyranoside 1a as a crystalline compound
in 79% yield, mp 120–122 ЊC; [α]D Ϫ36.0 (c 1.0, CHCl3).† Form-
ation of compound 1a was evident from the 1H NMR spectrum
† Units for [α]D-values are 10Ϫ1 deg cm2 gϪ1
.
‡ Boc = tert-butoxycarbonyl.
J. Chem. Soc., Perkin Trans. 1, 1997
3179

View Article Online
organic phase was washed successively with water and saturated
O
OH
aq. NaHCO3, dried (anhydrous Na2SO4), and concentrated to a
residue, which was recrystallised from dichloromethane–hexane
to obtain the title compound 1a (1.3 g, 79%) as needles, mp
120–122 ЊC (Found: C, 52.32; H, 5.48. C17H21NO7S requires C,
53.26; H, 5.52%); [α]D Ϫ36.0 (c 1.0, CHCl3); δH(200 MHz;
CDCl3) 1.20 (3 H, d, J 6.3, 6-H3), 2.0, 2.1 and 2.2 (9 H, 3 s,
OAc), 3.95 (1 H, m, 5-H), 5.10–5.40 (3 H, m, 2-, 3- and 4-H),
5.80 (1 H, d, J 10, 1-H) and 6.90–8.50 (4 H, m, ArH).
2 Boc-Ser-OMe
3 Boc-Thr-OMe
4 Boc-Tyr-OMe
O
O
SPy
OR
O
OR
O
OR
O
1a R = Ac
1b R = Bn
5
O
O
Ph
O
O
O
O
2-Pyridyl 2,3,4-tri-O-benzyl-1-thio-â-L-fucopyranoside 1b
Compound 1a (1.3 g, 3.3 mmol) was deacetylated by reaction
with cat. NaOMe–MeOH at room temp. for 6 h, the product
was neutralised with carbon dioxide, and the solvent was
removed to obtain 2-pyridyl 1-thio-α--fucopyranoside (0.8 g,
92.6%), which was dried at 60 ЊC for 3 h, dissolved in DMF (3
cm3), and sodium hydride (0.33 g, 14 mmol) was added followed
by benzyl bromide (1.36 cm3, 11.2 mmol) at 0 ЊC and the mix-
ture was stirred for 3 h. When TLC indicated completion of the
reaction, excess of NaH was decomposed by addition of
methanol (1 cm3), and the mixture was diluted with water (100
cm3) and extracted into dichloromethane (2 × 50 cm3). The
organic phase was washed with water, dried, and concentrated
to yield a syrup, which was purified by filtration on a bed of
silica gel [60–120 mesh; hexane–ethyl acetate (7:1)] to obtain
the title compound 1b (1.2 g, 76%) as yellow needles, mp 134–
136 ЊC (Found: C, 72.79; H, 6.21. C32H33NO4S requires C,
72.84; H, 6.30%); [α]D Ϫ15 (c 1.0, CHCl3); δH(200 MHz; CDCl3)
1.25 (3 H, d, J 6.3, 6-H3), 3.55–5.15 (10 H, m, 2–5-H,
3 × OCH2Ph), 5.39 (1 H, d, J 10.0, 1-H) and 6.90–8.50 (19 H,
m, ArH).
HO
O
H
HO
AcHN
OBn
O
6
7
CO2Me
NHBoc
CO2Me
NHBoc
O
O
O
O
OBn
OBn
OBn
OBn
BnO
BnO
8
9
O
CO2Me
NHBoc
O
OBn
OBn
BnO
10
O
O
O
N-Boc-3-O-(2,3,4-tri-O-benzyl-á-L-fucopyranosyl)-L-serine
methyl ester 8
O
O
O
O
O
H
O
A mixture of compound 1b (0.2 g, 0.38 mmol), N-(tert-
butoxycarbonyl)--serine methyl ester 2 (0.08 g, 0.38 mmol) and
powdered 4 Å molecular sieves (20 mg) in dry dichloromethane
(5 cm3) containing 5% iodomethane was heated to 50 ЊC for 62
h. Reaction was monitored by TLC and when complete the
reaction mixture was filtered on Celite, the filter was washed
with ethyl acetate (15 cm3) and the combined filtrate and wash-
ings were concentrated to obtain a residue, which was chrom-
atographed [SiO2; hexane–ethyl acetate (9:1)] to obtain the title
compound 8 (0.19 g, 79%) as a syrup (Found: C, 67.92; H, 7.04.
C36H45NO9 requires C, 68.01; H, 7.14%); [α]D Ϫ31 (c 1.0,
CHCl3); δH(400 MHz; CDCl3) 1.05 (3 H, d, J 6.4, 6Ј-H3), 1.45
(9 H, s, CMe3), 3.45–4.80 (12 H, m, 2-H, 3-H2, 2Ј–5Ј-H and
2.5 × OCH2Ph), 3.69 (3 H, s, OCH3), 4.82 (1 H, d, J1Ј,2Ј 3.8, 1Ј-
H), 4.87 (1 H, d, Jgem 11.6, OCH2Ph), 5.81 (1 H, d, J 9.0, NH)
and 7.20–7.45 (15 H, m, ArH); δC(50 MHz; CDCl3) 16.52
(C-6Ј), 28.35 (CMe3), 52.14 (OCH3), 54.95 (C-2), 68.90 (C-3),
72.30, 72.98, 73.80 and 74.82 (C-5Ј, 3 × OCH2Ph), 76.02 (C-2Ј),
77.45 (C-3Ј), 79.10 (C-4Ј), 94.53 (C-1Ј), 127.3–138.52 (aro-
matic), 156.34 (C᎐O, carbamate) and 171.85 (C᎐O, ester).
O
O
O
O
O
OBn
OBn
OBn
OBn
O
BnO
BnO
11
12
Ph
O
O
O
AcHN
OBn
O
OBn
OBn
BnO
13
Experimental
1H NMR spectra were measured with a Varian Gemini (200
and 400 MHz) spectrometer, with tetramethylsilane as internal
standard for solutions in deuteriochloroform. J-Values are
given in Hz. 13C NMR spectra were taken with a Varian Gemini
(50 MHz) spectrometer with CDCl3 as internal standard (δC
77.0) for solutions in deuteriochloroform. Optical rotations
were measured with a JASCO DIP-370 instrument. Organic
solutions were dried over anhydrous Na2SO4 and concentrated
below 40 ЊC in vacuo.
᎐
᎐
N-Boc-3-O-(2,3,4-tri-O-benzyl-á-L-fucopyranosyl)-L-threonine
methyl ester 9
A mixture of compound 1b (0.3 g, 0.57 mmol), N-(tert-
butoxycarbonyl)--threonine methyl ester 3 (0.12 g, 0.57 mmol)
and powdered 4 Å molecular sieves (15 mg) in dry dichloro-
methane (10 cm3) containing 5% iodomethane was heated to
50 ЊC for 60 h. When TLC indicated completion of the reaction,
the mixture was filtered on Celite, the filter was washed with
ethyl acetate (15 cm3) and the combined filtrate and washings
were concentrated to obtain a residue, which was chromato-
graphed [SiO2; hexane–ethyl acetate (9:1)] to obtain the title
compound 9 (0.18 g, 73%) as a syrup (Found: C, 68.29; H, 7.17.
C37H47NO9 requires C, 68.39; H, 7.29%); [α]D Ϫ42 (c 1.0,
CHCl3); δH(400 MHz; CDCl3) 1.05 (3 H, d, J 6.3, 6Ј-H3), 1.19 (3
H, d, J 6.7, 4-CH3), 1.46 (9 H, s, CMe3), 3.40–4.80 (11 H, m, 2-
2-Pyridyl 2,3,4-tri-O-acetyl-1-thio-â-L-fucopyranoside 1a
To a solution of 2-mercaptopyridine (0.6 g, 5.4 mmol) in dry
acetone (15 cm3) was added anhydrous K2CO3 (0.75 g, 5.4
mmol) and the mixture was stirred at room temperature for 30
min. α-Acetobromofucose15 (1.6 g, 4.5 mmol) as a solution in
dry toluene (10 cm3) was added to the above reaction mixture
and the mixture was stirred for 4 h at room temp. The reaction
mixture was diluted with toluene (20 cm3) and filtered, and the
3180
J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online
and 3-H, 2Ј–5Ј-H and 2.5 × OCH2Ph), 3.19 (3 H, s, OCH3),
4.81 (1 H, d, J1Ј,2Ј 3.8, 1Ј-H), 4.85 (1 H, d, Jgem 12.0, OCH2Ph),
5.35 (1 H, d, J 9.6, NH) and 7.2–7.45 (15 H, m, ArH); δC(50
MHz; CDCl3) 15.83 (C-4), 16.58 (C-6Ј), 28.32 (CMe3), 52.11
(OCH3), 58.32 (C-2), 66.70 (C-3), 72.11 (C-5Ј), 74.76, 73.20,
72.97 (3 × OCH2Ph), 76.0 (C-2Ј), 77.43 (C-3Ј), 78.90 (C-4Ј),
2 × OCMe2), 3.5–5.0 (17 H, m, 2–5-H, 6-H2, 1Ј–5Ј-H and
3 × OCH2Ph), 5.80 (1 H, d, J 4.6, 1-H) and 7.2–7.45 (15 H, m,
ArH); δC(50 MHz; CDCl3) 16.8 (C-6Ј), 25.6, 26.5, 26.8 and 27.0
(4 × CH3), 67.2, 68.1, 72.4, 73.3, 74.0, 75.1, 76.7, 78.1, 79.5,
81.4 and 82.5 (C-2–6, C-2Ј–5Ј, 3 × OCH2Ph), 96.2 (C-1Ј), 105.6
(C-1), 109.3 and 112.1 (2 × OCMe2) and 127–139 (aromatic).
94.84 (C-1Ј), 127.4–138.52 (arom.), 156.36 (C᎐O, carbamate)
᎐
Benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-3-O-(2,3,4-tri-
O-benzyl-á-L-fucopyranosyl)-á-D-glucopyranoside 13
and 171.54 (C᎐O, ester).
᎐
A mixture of compound 1b (0.155 g, 0.29 mmol), benzyl 2-
N-Boc-3-O-(2,3,4-tri-O-benzyl-á-L-fucopyranosyl)-L-tyrosine
methyl ester 10
acetamido-4,6-O-benzylidene-2-deoxy-α--glucopyranoside
7
(0.118 g, 0.29 mmol) and powdered 4 Å molecular sieves (10 mg)
in dry dichloromethane (10 cm3) containing 5% iodomethane
was heated to 50 ЊC for 60 h. Reaction was monitored by TLC
and when complete the reaction mixture was filtered on Celite,
the filter was washed with ethyl acetate (10 cm3), and the com-
bined washings and filtrate concentrated to obtain a residue,
which was chromatographed [SiO2; hexane–ethyl acetate (3:1)]
to obtain the title disaccharide 13 (0.18 g, 76%) as a crystalline
solid, mp 183–184 ЊC (Found: C, 73.45; H, 6.62. C49H53NO9
requires C, 73.56; H, 6.67%); [α]D Ϫ30.6 (c 1.0, CHCl3); δH(400
MHz; CDCl3) 1.07 (3 H, d, J 3.67, 6Ј-H3), 1.25 [3 H, br s,
A mixture of compound 1b (0.2 g, 0.38 mmol), N-(tert-
butoxycarbonyl)--tyrosine methyl ester 4 (0.1 g, 0.38 mmol)
and powdered 4 Å molecular sieves (15 mg) in dry dichloro-
methane (5 cm3) containing 5% iodomethane was heated to
50 ЊC for 78 h. When TLC indicated completion of the reaction,
the mixture was filtered on Celite, the filter was washed with
ethyl acetate (15 cm3), the combined filtrate and washings were
concentrated to obtain a residue, which was chromatographed
[SiO2; hexane–ethyl acetate (9:1)] to obtain the title compound
10 (0.2 g, 76%) as a crystalline solid, mp 106–107 ЊC (Found: C,
71.02; H, 6.77. C42H49NO9 requires C, 71.16; H, 6.82%); [α]D
Ϫ44 (c 1.0, CHCl3); δH(400 MHz; CDCl3) 1.05 (3 H, d, J 6.7,
6Ј-H3), 1.41 (9 H, s, CMe3), 3.02 (2 H, m, 3-H2), 3.71 (3 H,
s, OCH3), 3.94–5.01 (12 H, m, NH, 2-H, 2Ј–5Ј-H and 3 ×
OCH2Ph), 5.39 (1 H, d, J 3.6, 1Ј-H) and 6.97–7.41 (19 H, m,
ArH); δC(50 MHz; CDCl3) 16.54 (C-6Ј), 28.23 (CMe3), 37.49
(C-3), 52.13 (OMe), 67.16 (C-2), 73.26, 74.90, 76.08, 77.62 and
79.18 (C-2Ј–5Ј, 3 × OCH2Ph), 96.40 (C-1Ј), 116.92 (C-6, -8),
N᎐C(OH)CH ], 3.62–5.0 (18 H, m, 2–5-H, 6-H , 2Ј–5Ј-H and
᎐
3
2
4 × OCH2Ph), 5.19 and 5.21 (2 H, 2 d, J 3.12 and 3.57, 1- and
1Ј-H), 5.59 (1 H, s, O2CHPh) and 7.2–7.45 (25 H, m, ArH);
δ (50 MHz; CDCl ) 16.7 (C-6Ј), 22.4 [N᎐C(OH)CH ], 54.0,
᎐
C
3
3
63.2, 67.6, 68.8, 70.0, 73.1, 74.5, 74.9, 75.8, 77.5, 78.1 and 82.0
(C-2–6, C-2Ј–5Ј and 4 × OCH2Ph), 97.2 and 99.4 (C-1, -1Ј),
100.0 (O CHPh), 125–138 (aromatic) and 170.3 (C᎐O).
᎐
2
127.4–138.8 (aromatic), 156.36 (C᎐O, carbamate) and 172.30
(C᎐O, ester).
᎐
᎐
Acknowledgements
S. R. G. and R. R. G. thank University Grants Commission,
New Delhi for financial support in the form of a Junior
Research Fellowship.
1,2:3,4-Di-O-isopropylidene-6-O-(2,3,4-tri-O-benzyl-á-L-fuco-
pyranosyl)-á-D-galactopyranose 11
A mixture of compound 1b (0.3 g, 0.57 mmol), 1,2:3,4-di-O-
isopropylidene-α-D-galactopyranose 5 (0.15 g, 0.57 mmol) and
powdered 4 Å molecular sieves (20 mg) in dry dichloromethane
(15 cm3) containing 5% iodomethane was heated to 50 ЊC for
48 h. Reaction was monitored by TLC and when complete the
reaction mixture was filtered on Celite, the filter was washed
with ethyl acetate (15 cm3), and the combined filtrate and wash-
ings were concentrated to obtain a residue, which was chromato-
graphed [SiO2; hexane–ethyl acetate (4:1)] to obtain the title
disaccharide 11 (0.3 g, 77%) as a crystalline solid, mp 115–
116 ЊC (lit.,10 116–117 ЊC) (Found: C, 69.08; H, 7.05. C39H48O10
requires C, 69.21; H, 7.15%); [α]D Ϫ118 (c 2.0, CH2Cl2) [lit.,10
Ϫ117 (c 2.0, CH2Cl2)]; δH(400 MHz; CDCl3) 1.15 (3 H, d, J 6.5,
6Ј-H3), 1.29, 1.32, 1.42 and 1.5 (12 H, 4 s, 2 × OCMe2), 3.5–5.0
(17 H, m, 2–5-H, 6-H2, 1Ј–5Ј-H and 3 × OCH2Ph), 5.51 (1 H, d,
J 5.0, 1-H) and 7.2–7.45 (15 H, m, ArH); δC(50 MHz; CDCl3)
16.6 (C-6Ј), 24.4, 24.8, 25.9 and 26.0 (4 × CH3), 65.2, 66.3, 70.4,
70.7, 72.7, 73.1, 74.6, 76.2, 76.3 and 79.2 (C-2–6, C-2Ј–5Ј, 3 ×
OCH2Ph), 96.1 (C-1Ј), 97.2 (C-1), 108.3 and 108.9 (2 × OCMe2)
and 127.0–138.0 (aromatic).
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1,2:5,6-Di-O-iospropylidene-3-O-(2,3,4-tri-O-benzyl-á-L-fuco-
pyranosyl)-á-D-glucofuranose 12
A mixture of compound 1b (0.25 g, 0.47 mmol), 1,2:5,6-di-O-
isopropylidene-α--glucofuranose 6 (0.13 g, 0.47 mmol) and
powdered 4 Å molecular sieves (20 mg) in dry dichloromethane
(15 cm3) containing 5% iodomethane was heated to 50 ЊC for
48 h. Reaction was monitored by TLC and when complete the
reaction mixture was filtered on Celite, the filter was washed
with ethyl acetate (10 cm3), and the combined filtrate and wash-
ings were concentrated to obtain a residue, which was chromato-
graphed [SiO2; hexane–ethyl acetate (5:1)] to obtain the title
disaccharide 12 (0.27 g, 85%) as a syrup (Found: C, 69.12; H,
7.04. Calc. for C39H48O10: C, 69.21; H, 7.15%); [α]D Ϫ102 (c 2.0,
CHCl3) [lit.,10 Ϫ98 (c 2.0, CHCl3)]; δH(400 MHz; CDCl3) 1.10
(3 H, d, J 6.0, 6Ј-H3), 1.22, 1.25, 1.36 and 1.46 (12 H, 4 s,
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Paper 7/04310D
Received 18th June 1997
Accepted 8th July 1997
3182
J. Chem. Soc., Perkin Trans. 1, 1997