Oligosaccharide analogues of polysaccharides. Part 18. Synthesis of cyclic hybrids of 2,2'-bipyridine and acetylenosaccharides

Article abstract of DOI:10.1002/(SICI)1522-2675(19990407)82:4<485::AID-HLCA485>3.0.CO;2-A

We report the efficient construction of cyclic hybrids of 2,2'- bipyridine and acetylenosaccharides from readily available building blocks involving a double Castro-Stephens coupling of an O-protected and an O- unprotected, mono-C-silylated 1,4-cis-diethy

Full text of DOI:10.1002/(SICI)1522-2675(19990407)82:4<485::AID-HLCA485>3.0.CO;2-A

Helvetica Chimica Acta ± Vol. 82 (1999)
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Oligosaccharide Analogues of Polysaccharides
1
Part 18 )
Synthesis of Cyclic Hybrids of 2,2'-Bipyridine and Acetylenosaccharides
by Roland Bürli and Andrea Vasella*
Laboratorium für Organische Chemie, ETH-Zentrum, Universitätstrasse 16, CH-8092 Zürich
We report the efficient construction of cyclic hybrids of 2,2'-bipyridine and acetylenosaccharides from
readily available building blocks involving a double Castro-Stephens coupling of an O-protected and an O-
unprotected, mono-C-silylated 1,4-cis-diethynylated 1,5-anhydroglucitol (see 2 and 6, resp.) to 6,6'-dibromo-
2,2'-bipyridine (1) followed by oxidative cyclization of the resulting dialkynes (see Scheme). UV Spectra of the
C-alkynylated linear and cyclized bipyridines 8 and 10 show that these ligands complex a range of metal ions
(Figs. 4 and 5).
1. Introduction. ± Cyclic host molecules, differing in geometric and physicochem-
ical properties of their cavity, are efficiently constructed from appropriate building
blocks [2]. Saccharides possess obvious advantages as enantiomerically pure, densely
functionalised, and readily derivatised building blocks. Apart from cycloglucans [3 ± 5],
consisting exclusively of saccharide units, there is a range of hosts embodying building
blocks derived from carbohydrate as well as non-carbohydrate sources, such as the
ꢀglycophanesꢁ [6] [7] and hosts obtained by combining saccharides with ethylenedioxy
groups [8 ± 12], butadiyne units [6] [13], and hydroxy acids [14]. In this context, the 2,2'-
bipyridine-6,6'-diyl group is attractive [15], as it readily forms complexes with metal
ions [16], and has proven useful in many applications [17]. We report the synthesis of a
cyclic host combining bipyridine and acetylenosaccharides as building blocks by
coupling 1,4-dialkynylated 1,6-anhydroglucitols with 6,6'-dibromo-2,2'-bipyridine (1).
2. Results and Discussion. ± Coupling the dibromo-bipyridine 1 [18] to the
2
Â
dibenzylated dialkyne 2 [19] under conditions reported by Kövari and Krämer [20] )
afforded the disubstituted bipyridine 3 in a yield of 78% (Scheme). Base-promoted
deacetylation and desilylation of 3 yielded 92% of the diol 4. Treatment of 4 with
Cu(OAc)2 in pyridine led to the macrocyclic bipyridine 5 in 59% yield.
1
The H-NMR spectra (CD2Cl2) of the linear and cyclic bipyridines 4 and 5 show
only one set of signals, in agreement with their C2 symmetry. The temperature
dependence of their spectra differs significantly. The signals of the macrocycle 5 show
considerable broadening below 408, while no line broadening was observed for 4
1
)
)
Part 17: [1].
2
Â
Kövari and Krämer coupled 1 with 5.8 equiv. of N,N-dimethylpropargylamine in 64% yield to 3,3'-[(2,2'-
bipyridine)-6,6'-diyl]bis[N,N-dimethylprop-2-ynamine]. By increasing the concentration of the coupling
partners, we secured a higher yield of 3 while reducing the excess of the alkyne 1 to 2.2 equiv.

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Scheme
a) [PdCl2(PPh3)2], CuI, PPh3, Et3N, [1] ˆ 0.3m: 2 ! 3, 78%; 6 ! 7; 70%. b) NaOH, MeOH; 92%. c) Cu(OAc)2,
pyridine: 4 ! 5, [4] < 0.27 mm, 59%; 8 ! 9, [8] < 0.9 mm; Ac2O, ca. 68%. d) NaOMe, MeOH, 93%. e) NaOMe,
MeOH, 73%.
upon cooling to 708 (Figs. 1 and 2). The specific rotation of 4 shows a strong and
linear temperature dependence (Fig. 3), while that of 5 depends very little on
temperature3).
Fig. 1. 1H-NMR Spectra (300 MHz, CD2Cl2, 6.4 mm) of 4 at 26 and 708
3
)
The specific rotation [a]405 of 5 (CHCl3) at 25 and 508 is 276.08 and 276.68, respectively.

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Fig. 2. 1H-NMR Spectra (300 MHz, CD2Cl2, 6.6 mm) of 5 at 20, 40, and 708
Force-field calculations (MM3*) [21] suggest that 5 adopts the two conformers
depicted in Fig. 3; line broadening suggests a slow transition between them. The
absence of line broadening and the strong temperature dependence of the specific
rotation of 4 suggest a rapid interconversion of conformers and a temperature-
dependent shift of the position of the equilibrium between them.
To test the feasibility of the Castro-Stephens coupling with unprotected acetyleno-
saccharides, we exposed 1 and the readily available diethynylated triol 6 [19] to the
same conditions that led to 4, and obtained the diethynylated bipyridine 7 in a yield of
70%. The Me3Si groups of 7 were removed with NaOMe in MeOH (93%), and the
resulting dialkyne 8 was treated with Cu(OAc)2 in pyridine. The crude product was
acetylated in situ to facilitate the removal of copper salts. Chromatography yielded
68% of the hexaacetate 9 as a bright-yellow solid. According to the 1H- and 13C-NMR
spectra, this material did not contain any organic impurity. However, deacetylation of 9
followed by selective precipitation from a solution in CH2Cl2/MeOH led to a colourless
hexaol 10 (73%).
We compared the UV spectra (Figs. 4 and 5) of aqueous solutions of the
unprotected bipyridines 8 and 10, in the presence and absence of metal ions, as
described by Sone et al. [22] for 2,2'-bipyridines.
Aqueous solutions of the ligands (L) 8 and 10 absorb strongly between l 270 and
330 nm, whereas the pure metal (M) solutions absorb only weakly between 250 and

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Fig. 3. Top: Calculated conformations of the bipyridine 5 (MM3*). The PhCH2 groups were replaced by Me
groups for clarity. The angles between the aromatic ring planes are 16.3 and 19.68, respectively. Bottom:
Temperature dependence of the specific rotation (at 405 nm in CHCl3) of the bipyridine 4.
400 nm. The UV spectra of both ligands show a significant bathochromic shift upon
addition of Cu(NO3)2 or AgNO3. A strong bathochromic shift is also observed for
the mixtures 8/NiCl2 and 10/ZnCl2. Addition of Pb(OAc)2, Co(NO3)2, MnSO4, or
Mg(NO3)2, however, had only a small effect. Although the extent of a bathochromic
shift is not directly correlated to the stability of a complex, a qualitative comparison
of the UV spectra suggests that the tendency to form complexes decreases for the
acyclic bipyridine 8 in the order Cu(NO3)2 > NiCl2 ꢀ AgNO3 > ZnCl2 ꢀ Pb(OAc)2 ꢀ
Co(NO3)2 > MnSO4 ꢀ Mg(NO3)2 and for the macrocyclic bipyridine 10 in the order
Cu(NO3)2 ꢀ ZnCl2 > AgNO3 ꢀ Pb(OAc)2 > NiCl2 > Co(NO3)2 ꢀ MnSO4 ꢀ Mg(NO3)2.
Unfortunately, none of these compounds crystallized in our hands, and the exact
structure of the complexes in solution has not been determined.
The strongest difference between the two ligands is observed for the complexation
of ZnCl2 and NiCl2. ZnCl2 causes only a weak change of the UV spectrum of 8, but
strongly affects the UV spectrum of the macrocycle 10, indicating that its complexation
depends strongly upon the enforced ꢀcisoidꢁ-conformation of the bipyridine unit in 10.
In contradistinction, NiCl2 causes a strong change of the UV spectrum of 8, but not of
10, indicating that NiCl2 forms 1:2 or 1:3 complexes [16] with bipyridines.
We thank the Swiss National Science Foundation and F. Hoffmann-La Roche AG, Basel, for generous
support.

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Fig. 4. UV Spectra of the mixtures of the linear bipyridine 8 (left) and the cyclic bipyridine 10 (right) with
Cu(NO3)2, AgNO3, ZnCl2, and NiCl2. Extinction vs. wavelengths [nm]; in H2O at 248. L: [ligand] ˆ 0.04 mm;
M: [metal salt] ꢀ 4 mm; ML: [ligand] ˆ 0.04 mm and [metal salt] ꢀ 4 mm.
Experimental Part
General (cf. [13a]). Workup: The mixture was diluted with the indicated solvent and a sat. aq. NH4Cl soln.,
the aq. layer extracted (3 ± 5 times) with the indicated solvent, and the combined org. phase washed once with
brine, dried (MgSO4), and evaporated. UV spectra (Figs. 4 and 5): the samples were prepared with SOCOREX-
SWISS (100 ± 1000 ml) pipettes from aq. solns. of 8, 10, AgNO3, Co(NO3)2, Cu(NO3)2, Mg(NO3)2, MnSO4,
NiCl2, Pb(OAc)2, and ZnCl2; solns.: [ligand] ˆ 0.08 mm; [metal salt] ꢀ 8 mm; H2O was not buffered and
purified with a Millipore apparatus. UV Spectra: UVIKON-931 spectrophotometer, quartz cell (1 cm) at ca. 248.
3,3'-[(2,2'-Bipyridine-6,6'-diyl)diethyne-2,1-diyl]bis[1-O-acetyl-2,6-anhydro-4,5-di-O-benzyl-3-deoxy-1-C-
(trimethylsilyl)-d-glycero-l-gulo-oct-7-ynitol] (3).
A degassed suspension of 1 (116 mg, 0.37 mmol),
[PdCl2(PPh3)2] (7.44 mg, 10.6 mmol), CuI (9.6 mg, 50.4 mmol), and PPh3 (7.68 mg, 29.2 mmol) in Et3N (1.2 ml)

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Fig. 5. UV Spectra of the mixtures of the linear bipyridine 8 (left) and the cyclic bipyridine 10 (right) with
Pb(OAc)2, Co(NO3)2, MnSO4 and Mg(NO3)2. Extinction vs. wavelengths [nm]; in H2O at 248. L: [ligand] ˆ
0.04 mm; M: [metal salt] ꢀ 4 mm; ML: [ligand] ˆ 0.04 mm and [metal salt] ꢀ 4 mm.
was stirred under N2 at r.t. for 5 min and treated with a soln. of 2 (400 mg, 0.81 mmol) in Et3N (1.2 ml). The
mixture was heated to 708, stirred for 2 h, cooled to 08, and diluted with a 5% aq. soln. of H2SO4 and CH2Cl2.
Workup (CH2Cl2) and FC (hexane/Et2O 7:3 ! 1 : 1) gave 3 (327 mg, 78%). Colourless oil. Rf (hexane/Et2O
2 : 3) 0.15. IR: 3089w, 3066w, 3007m, 2960w, 2903w, 2234w, 2170w, 1739s(br.), 1569m, 1436s, 1367m, 1119s(br.),
1037m, 908m(br.), 846s. 1 H-NMR (300 MHz, CDCl3): 8.39 (dd, J ˆ 1.0, 8.0, H C(3'')); 7.73 (t, J ˆ 7.8,
H
C(4'')); 7.50 ± 7.47 (m, H C(5''),
1
arom. H); 7.43 ± 7.24 (m, 9 arom. H); 5.06 (d, J ˆ 10.6, PhCH);
4.98 (d, J ˆ 10.6, PhCH); 4.86 (d, J ˆ 5.6,
H
C(6)); 4.78 (d, J ˆ 11.9, PhCH); 4.72 (d, J ˆ 12.0, PhCH);
4.48 (br. d, J ꢀ 11.2, H C(1)); 4.47 (br. d, J ꢀ 11.2, H' C(1)); 4.32 (td, J ꢀ 3.7, 10.5, H C(2)); 4.03 (dd, J ˆ
9.3, 10.3, H C(4)); 3.58 (dd, J ˆ 5.7, 9.2, H C(5)); 2.95 (br. t, J ꢀ 10.5, H C(3)); 2.11 (s, Ac); 0.26 (s, Me3Si).
4
13C-NMR (75 MHz, CDCl3): 170.83 (s, CˆO); 155.68 (s, C(2'')); 142.36 (s, C(6'')) ); 138.31, 138.17(2s);
4
)
The assignment of the signals of C(2'') and C(6'') is based on a comparison with similar bipyridines [23].

Helvetica Chimica Acta ± Vol. 82 (1999)
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137.06 (d, C(4'')); 128.54 (d, 2 C); 128.40 (d, 2 C); 128.33 (d, 2 C); 127.79(d); 127.74(d); 127.68 (d, 2 C);
127.57(d); 120.71(d); 99.64 (s, C(7)); 95.58 (s, C(8)); 85.99, 83.90 (2s, 2 C ꢁ C); 79.60, 78.71 (2d, C(4), C(5));
75.90, 72.55 (2t, 2 PhCH2); 71.93 (d, C(2)); 67.53 (d, C(6)); 64.52 (t, C(1)); 37.69 (d, C(3)); 20.93 (q, Me);
‡
0.03 (q, Me3Si). MS-FAB: 1133 (100, [M ‡ H] ), 915(11).
3,3'-[(2,2'-Bipyridine-6,6'-diyl)diethyne-2,1-diyl]bis[2,6-anhydro-4,5-di-O-benzyl-3-deoxy-d-glycero-d-gulo-
oct-7-ynitol] (4). A soln. of 3 (322 mg, 0.28 mmol) in MeOH (30 ml) was treated at 08 under N2 with a 0.1m
‡
NaOH soln. in MeOH (6 ml), warmed to r.t., stirred for 1 h, and treated with Dowex (H form). The solids were
filtered off and washed (MeOH). Evaporation of the filtrate and FC (hexane/AcOEt 1 :1) of the residue left 4
(238 mg, 92%). White foam. Rf (hexane/AcOEt 1 :1) 0.16. [a]2d5ˆ 108.0 (c ˆ 0.68, CHCl3). UV (CH2Cl2,
12.3 mm): 302(15870), 272(5450), 228(29200). IR: 3597w, 3450w(br.), 3304m, 3007m, 2930w, 2876w, 2234w,
2120w, 1570m, 1496w, 1436s, 1364w, 1078s(br.), 1027m(br.). 1H-NMR (500 MHz, CDCl3): 8.35 (dd, J ˆ 1.1, 8.0,
H
C(3'')); 7.70 (t, J ˆ 7.8, H C(4'')); 7.48 ± 7.45 (m, H C(5''), 1 arom. H); 7.39 ± 7.22 (m, 9 arom. H);
5.08 (d, J ˆ 10.6, PhCH); 4.97 (d, J ˆ 10.6, PhCH); 4.80 (d, J ˆ 11.9, PhCH); 4.77 (dd, J ˆ 2.3, 5.7, H C(6));
4.72 (d, J ˆ 11.9, PhCH); 4.18 (ddd, J ˆ 2.5, 5.1, 10.6, H C(2)); 4.07 (dd, J ˆ 9.2, 10.3, H C(4)); 4.01 (ddd, J ˆ
2.5, 6.5, 12.0, H C(1)); 3.87 (ddd, J ˆ 5.1, 6.5, 11.9, H' C(1)); 3.55 (dd, J ˆ 5.7, 9.2, H C(5)); 2.92 (br. t, J ꢀ
10.5,
H
C(3)); 2.65 (d, J ˆ 2.3,
H
C(8)); 1.99 (t, J ˆ 6.5, OH). 13C-NMR (125 MHz, CDCl3):
155.67 (s, C(2'')); 142.32 (s, C(6'')); 138.41, 137.82(2s); 137.02 (d, C(4'')); 128.50 (d, 2 C); 128.31 (d, 2 C);
128.28 (d, 2 C); 127.98(d); 127.93 (d, 2 C); 127.69(d); 127.34(d); 120.69(d); 86.25, 83.82 (2s, C ꢁ C); 80.06,
78.49 (2d, C(4), C(5)); 78.31 (d, C(8)); 77.80 (s, C(7)); 76.01 (t, PhCH2); 74.27 (d, C(2)); 73.19 (t, PhCH2);
‡
‡
67.02 (d, C(6)); 63.48 (t, C(1)); 37.55 (d, C(3)). FAB-MS: 1810 (13, [2M ‡ H] ), 905 (100, [M ‡ H] ). Anal.
calc. for C58H52N2O8 ´ 0.5 H2O (914.06): C 76.21, H 5.84, N 3.06; found: C 76.20, H 5.84, N 2.95.
2,6 :11,15-Dianhydro-4,5,12,13-tetra-O-benzyl-3,14-C-[(2,2'-bipyridine-6,6'-diyl)diethyne-2,1-diyl]-3,7,8,9,
10,14-hexadeoxy-d-erythro-l-ido-l-gulo-hexadeca-7,9-diynitol (5). A degassed soln. of Cu(OAc)2 (449 mg,
2.47 mmol) in pyridine (450 ml) was treated at 508 under N2 with a soln. of 4 (112 mg, 0.12 mmol) in pyridine
(1 ml) within 10 h, stirred for 20 h, and evaporated. The residue was dissolved in CH2Cl2 (20 ml) and a sat. aq.
KCN soln. (7 ml) and stirred for ca. 12 h. Workup (CH2Cl2) and FC (twice: 1. CH2Cl2/MeOH 49 :1; 2. CHCl3/
AcOEt 4 :1) gave 5 (66 mg, 59%). White solid. Rf (AcOEt) ca. 0.26. M.p. 189 ± 1918 (dec.). IR: 3602m,
3444w(br.), 3007m, 2924m, 2232w, 2150w, 1601m, 1581m, 1564m, 1496m, 1149s, 1364m, 1332m, 1117s(br.),
1077s, 1016m. 1H-NMR (300 MHz, CDCl3): 7.83 ± 7.79 (m, H C(3'), H C(4')); 7.44 (dd, J ˆ 2.5, 6.1, H C(5'));
7.36 ± 7.23 (m, 10 arom. H); 5.10 (d, J ˆ 11.5, PhCH); 4.98 (d, J ˆ 11.4, PhCH); 4.85 (d, J ˆ 5.5, H C(6));
4.72 (d, J ˆ 12.1, PhCH); 4.65 (d, J ˆ 12.1, PhCH); 4.40 (ddd, J ˆ 2.1, 4.2, 10.5, H C(2)); 4.28 (t, J ˆ 9.7,
H
C(4)); 3.98 (br. ddd, J ꢀ 2.1, 5.0, 11.9, H C(1)); 3.89 (br. ddd, J ꢀ 4.2, 6.2, 11.9, H' C(1)); 3.53 (dd, J ˆ
5.5, 9.5, H C(5)); 2.93 (br. t, J ꢀ 10.4, H C(3)); 2.02 (br. t, J ꢀ 6.0, OH). 13C-NMR (75 MHz, CDCl3):
154.75 (s, C(2')); 144.25 (s, C(6')); 139.03, 137.84(2s); 137.52 (d, C(4')); 128.54 (d, 2 C); 128.21 (d, 2 C);
127.97 (d, 2 C); 127.59 (d, 2 C); 127.52(d); 127.35(d); 126.39(d); 120.61(d); 88.14, 82.99 (2 s, C ꢁ C); 80.42,
79.02 (2d, C(4), C(5)); 75.77 (t, PhCH2); 74.62 (d, C(2)); 74.51, 73.14 (2s, C(7), C(8)); 73.06 (t, PhCH2);
‡
67.45 (d, C(6)); 63.38 (t, C(1)); 37.00 (d, C(3)). MS-FAB: 903 (100, [M ‡ H] ).
3,3'-[(2,2'-Bipyridine-6,6'-diyl)diethyne-2,1-diyl]bis[2,6-anhydro-3-deoxy-1-C-(trimethylsilyl)-d-glycero-l-
gulo-oct-7-ynitol] (7). A degassed suspension of 1 (1.17 g, 3.73 mmol), [PdCl2(PPh3)2] (47 mg, 67.1 mmol), CuI
(44 mg, 0.23 mmol), and PPh3 (43 mg, 0.16 mmol) in Et3N (12 ml) was stirred for 10 min at r.t. under N2, treated
within 10 min with a soln. of 6 (2.20 g, 8.20 mmol) in Et3N (12 ml), heated to 708, stirred for 9 h, and evaporated.
FC (supported on SiO2 as a solid; CHCl3/MeOH 20 :1) of the residue gave 7 (1.80 g, 70%). White solid. Rf
(AcOEt/MeOH 7:3) 0.65. M.p. 147 ± 1488. [a]2d5ˆ 67.3 (c ˆ 1.08, MeOH). IR (KBr): 3680 ± 3000s (br., max. at
3380), 2957m, 2232m, 2169m, 1636m, 1571s, 1436s, 1334m, 1250s, 1124m, 1076s(br.), 901m, 844s(br.), 802m,
761m, 710w, 639w, 577w. 1H-NMR (300 MHz, CD3OD): 8.25 (dd, J ˆ 0.9, 8.0, H C(3'')); 7.92 (t, J ˆ 7.8,
H
C(4'')); 7.57 (dd, J ˆ 0.9, 7.8, H C(5'')); 4.76 (d, J ˆ 5.6, H C(6)); 4.08 (ddd, J ˆ 2.2, 4.7, 10.4, H C(2));
3.93 (dd, J ꢀ 2.2, 12.1, H C(1)); 3.92 (br. t, J ꢀ 10.0, H C(4)); 3.85 (dd, J ˆ 4.7, 12.1, H' C(1)); 3.50 (dd, J ˆ
5.9, 9.3, H C(5)); 2.77 (br. t, J ꢀ 10.3, H C(3)); 0.20 (s, Me3Si). 13C-NMR (75 MHz, CD3OD): 157.37
(s, C(2'')); 144.43 (s, C(6'')); 139.29 (d, C(4'')); 129.08, 122.30 (2d, C(3''), C(5'')); 102.06 (s, C(7)); 95.62
(s, C(8)); 88.96, 84.25 (2s, C ꢁ C); 76.31 (d, C(2)); 73.86, 72.80 (2d, C(4), C(5)); 70.76 (d, C(6)); 64.04
‡
(t, C(1)); 39.71 (d, C(3));
H2O (706.93): C 61.16, H 6.56, N 3.96; found: C 60.94, H 6.53, N 4.06.
0.02 (q, Me3Si). MALDI-MS: 689 ([M ‡ H] ). Anal. calc. for C36H44N2O8Si2 ´
3,3'-[(2,2'-Bipyridine-6,6'diyl)diethyne-2,1-diyl]bis[2,6-anhydro-3-deoxy-d-glycero-l-gulo-oct-7-ynitol] (8).
A soln. of 7 (1.80 g, 2.61 mmol) in MeOH (10 ml) was treated at 08 under N2 with a 2% NaOMe soln. in
‡
MeOH (3.5 ml), stirred for 3 h, and neutralized with Dowex (H form). The solids were filtered off and washed
(MeOH). Evaporation of the filtrate left 8 (1.32 g, 93%). White solid. Rf (AcOEt/MeOH 7:3) 0.44. M.p. 215±

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2168. [a]2d5ˆ 43.3 (c ˆ 0.78, DMSO). UV (MeOH, 51 mm): 301(19166). IR: 3620 ± 3000s (br., max. at 3350),
3289w, 2921m, 2231m, 2113w, 1640w, 1568s, 1438s, 1363m, 1274w, 1123s, 1076s(br.), 918w, 881m, 833w, 801s,
680m(br.). 1H-NMR (300 MHz, CD3OD): 8.25 (dd, J ˆ 1.3, 8.1, H C(3'')); 7.91 (br. t, J ꢀ 7.8, H C(4''));
7.57 (dd, J ˆ 1.0, 7.6, H C(5'')); 4.78 (dd, J ˆ 2.2, 5.6, H C(6)); 4.10 (ddd, J ˆ 2.2, 4.4, 10.3, H C(2)); 3.94 (br.
t, J ꢀ 9.7, H C(4)); 3.92 (dd, J ˆ 2.2, 12.1, H C(1)); 3.85 (dd, J ˆ 4.6, 12.1, H' C(1)); 3.52 (dd, J ˆ 5.6, 9.3,
H
C(5)); 3.04 (d, J ˆ 2.4,
H
C(8)); 2.77 (br. t, J ꢀ 10.3,
H
C(3)). 13C-NMR (75 MHz, (D6)DMSO):
155.03 (s, C(2'')); 142.51 (s, C(6'')); 138.14 (d, C(4'')); 127.97, 120.23 (2d, C(3''), C(5'')); 88.86, 82.49,
79.87 (3s, C(7), C ꢁ C); 79.43 (d, C(8)); 74.95 (d, C(2)); 71.65, 71.12 (2d, C(4), C(5)); 68.32 (d, C(6));
‡
62.01 (t, C(1)); 37.82 (d, C(3)). CI-MS: 545 (40, [M ‡ H] ), 459(100), 373(63), 279(24). FAB-MS: 545 (40,
‡
[M ‡ H] ), 459(100), 373(63), 345(27), 279(24), 97(20). Anal. calc. for C30H28N2O8 ´ H2O (562.57): C 64.05,
H 5.37, N 4.98; found: C 63.75, H 5.67, N 4.80.
1,4,5,12,13,16-Hexa-O-acetyl-2,6 :11,15-dianhydro-3,14-C-[(2,2'-bipyridine-6,6'-diyl)diethyne-2,1-diyl]-3,7,-
8,9,10,14-hexadeoxy-d-erythro-l-ido-l-gulo-hexadeca-7,9-diynitol (9). At 508 under N2, a degassed soln. of
Cu(OAc)2 (3.33 g, 18.36 mmol) in pyridine (1.00 l) was treated dropwise with a soln. of 8 (0.50 g, 0.92 mmol) in
pyridine (10 ml) within 12 h. The mixture was stirred for 14 h and evaporated slowly within 6 h. The residue was
dissolved in pyridine (40 ml) and Ac2O (20 ml), stirred for ca. 12 h at r.t. under N2, and evaporated. The residue
was dissolved in AcOEt and a sat. aq. KCN soln. The layers were separated, and the aq. layer was extracted (7 Â
with AcOEt). Workup (AcOEt) of the combined org. phases and FC (twice: 1. CH2Cl2/EtOH 99 : 1; CH2Cl2/
AcOEt 9 : 1) gave 9 (499 mg, ca. 68%). Intensly yellow solid. Rf (AcOEt/MeOH 9 : 1) 0.27. M.p. > 1778 (dec.).
IR: 2965w, 2237w, 2135w, 1747s (br.), 1581w, 1565m, 1463w, 1441m, 1370m, 1069m(br.), 1051m, 908m.
1H-NMR (500 MHz, CDCl3): 7.81 (dd, J ˆ 1.1, 7.9, H C(3')); 7.77 (br. t, J ˆ 7.5, H C(4')); 7.41 (dd, J ˆ 1.2,
7.5, H C(5')); 5.62 (br. t, J ꢀ 10.1, H C(4)); 5.05 (d, J ˆ 5.7, H C(6)); 4.95 (dd, J ˆ 5.7, 9.8, H C(5));
4.67 (ddd, J ˆ 2.2, 4.1, 10.6, H C(2)); 4.50 (dd, J ˆ 2.4, 12.4, H C(1)); 4.45 (dd, J ˆ 4.2, 12.4, H' C(1));
3.07 (br. t, J ꢀ 10.5, H C(3)); 2.14, 2.11, 2.05 (3s, 3 Ac). 13C-NMR (125 MHz, CDCl3): 170.76, 170.38,
168.98 (3s, 3 CˆO); 154.71 (s, C(2')); 143.45 (s, C(6')); 137.27 (d, C(4')); 126.45, 120.70 (2d, C(3'), C(5'));
84.26, 84.00, 73.58, 73.36 (4s, 2 C ꢁ C); 72.50, 71.62, 70.35 (3d, C(2), C(4), C(5)); 66.46 (d, C(6));
‡
64.21 (t, C(1)); 35.80 (d, C(3)); 20.95, 20.86, 20.82 (3q, 3 Me). FAB-MS: 1589 (1, [2M ‡ H] ), 795 (100,
‡
[M ‡ H] ).
2,6 :11,15-Dianhydro-3,14-C-[(2,2'-bipyridine-6,6'-diyl)diethyne-2,1-diyl]-3,7,8,9,10,14-hexadeoxy-d-eryth-
ro-l-ido-l-gulo-hexadeca-7,9-diynitol (10). A soln. of 9 (440 mg, 0.55 mmol) in MeOH (20 ml) was treated at 48
‡
under Ar with a 2% NaOMe soln. in MeOH, stirred at r.t. for 17 h, and neutralized with Dowex (H form). The
solids were filtered off and washed (MeOH). The filtrate was concentrated to ca. 4 ml, treated with CH2Cl2, and
left for ca. 12 h. The precipitated solids were filtered off and washed (CH2Cl2: ! 10, 206 mg, 69%). The mother
liquor was evaporated und the residue dissolved in MeOH and treated with CH2Cl2 ( ! 10, 13 mg, 4%). White
solid. Rf (AcOEt/MeOH 7: 3) ca. 0.11. M.p. > 2878 (dec.). [a]2d5ˆ 15 (c ˆ 0.41, DMSO). IR (KBr): 3600 ±
3044s (br., max. at 3344), 2917w, 2229m, 2130w, 1582m, 1562m, 1461m, 1326w, 1137m, 1087s, 1068s, 1043s, 990w,
802m. UV (MeOH, 0.1 mm): 310(12136), 286(8607). 1H-NMR (400 MHz, (D6)DMSO): 8.12 (br. dd, J ꢀ 0.5,
7.8, H C(3')); 7.95 (t, J ˆ 7.8, H C(4')); 7.55 (dd, J ˆ 0.5, 7.8, H C(5')); 5.64 (d, J ˆ 4.6, exchange with D2O,
HO C(5)); 5.58 (d, J ˆ 6.1, exchange with D2O, HO C(4)); 4.85 (br. dd, J ꢀ 5.5, 7.0, exchange with D2O,
HO C(1)); 4.89 (d, J ˆ 5.6, H C(6)); 3.98 (ddd, J ˆ 1.6, 5.2, 10.6, H C(2)); 3.79 ± 3.72 (m, addn. of D2O !
change of signal, H C(4), H C(1)); 3.57 (br. ddd, J ꢀ 5.5, 6.3, 12.1, addn. of D2O ! br. dd, J ꢀ 5.5, 12.4,
H' C(1)); 3.37 (br. td, J ꢀ 5.3, 9.6, addn. of D2O ! dd, J ˆ 5.6, 9.3, H C(5)); 2.57 (br. t, J ꢀ 10.4, H C(3)).
13C-NMR (100 MHz, (D6)DMSO): 154.41 (s, C(2')); 142.51 (s, C(6')); 137.85 (d, C(4')); 125.86, 120.95
(2d, C(3'), C(5')); 88.55, 82.28, 76.02, 71.55 (4s, 2 C ꢁ C); 75.99 (d, C(2)); 72.10, 70.85 (2d, C(4), C(5));
‡
69.01 (d, C(6)); 62.07 (t, C(1)); 37.70 (d, C(3)). MALDI-MS: 543 ([M ‡ H] ). Anal. calc. for C30H26N2O8 ´ 2.5
H2O (587.57): C 61.32, H 5.32, N 4.77; found: C 61.14, H 5.04, N 4.84.
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Received January 4, 1999