2602
L. A. Mulard et al. / Tetrahedron 58 02002) 2593±2604
mmol) and donor12 8 ,1.80 g, 2.41 mmol) in anhydrous Et2O
was treated with TMSOTf as described above for the
preparation of 23. The crude mixture was roughly puri®ed
by chromatography yielding contaminated 23 ,2.19 g). 1N
methanolic sodium methoxide was added dropwise to a
solution of the latter ,2.04 g) in methanol ,20 mL) until
pH 10 was reached. The mixture was stirred at rt for 7 h
when TLC ,solvent C, 4:1) showed that no starting material
remained. Neutralization with resin IR 120 ,H1) followed
by column chromatography ,solvent A, 49:1) of the crude
material gave diol 24 ,1.53 g, 81%) as a white foam;
3.73 ,C-3C), 67.7 ,C-5D), 67.6 ,C-5A), 67.4 ,C-5C), 62.2 ,C-
6D), 56.9 ,C-2D), 54.5 ,OCH3), 29.1,CCH ), 23.2, 21.1
,C,O)CH3), 19.1 ,CCH3), 17.9 ,C-6C), and 17.8 ,C-6A).
3
Crude 3 ,990 mg, 1.07 mmol) and donor 2 ,1.54 g,
1.5 mmol) were dissolved in anhydrous Et2O ,10 mL) and
the solution was cooled to 2788C. TMSOTf ,20 mL,
100 mmol) was added, and the reaction mixture was stirred
overnight while the bath temperature was slowly coming
back to rt. TLC ,solvent A, 97:3) showed that only little
acceptor remained, Et3N was added and volatiles were
evaporated. Chromatography ,solvent A, 12:1) provided
the fully protected pentasaccharide 25 ,1.28 g, 67%) as a
white foam; [a]D1248 ,c 1.0); NMR: 1H, d 8.13±7.05 ,m,
45H, Ph), 5.70 ,bs, 1H, H-2B), 5.60 ,d, 1H, JNH,27.7 Hz,
NH), 5.21,d, 1H, J1,23.5 Hz, H-1E), 5.20 ,bs, 1H, H-1B),
4.99 ,bd, 1H, J1,21.7 Hz, H-2C), 4.98±4.36 ,m, 15H,
OCH2), 4.82 ,d, overlapped, 1H, H-1D), 4.69 ,bs, 1H,
H-1C), 4.66 ,bs, 1H, H-1A), 4.34 ,dd, 1H, J2,33.0 Hz,
J1,29.5 Hz, H-3B), 4.24 ,d, 1H, J12.1 Hz, OCH2), 4.13
,dd, 1H, J2,33.2 Hz, J3,49.5 Hz, H-3C), 4.06±3.85 ,m,
8H, H-3E, 5E, 5C, 3D, 6aD, 2A, 5B, 3A), 3.75±3.41,m, 10H,
H-6bD, 4E, 4B, 5A, 6aE, 2E, 4D, 6bE, 4C, 2D), 3.38 ,pt, 1H,
J3,4J4,59.3 Hz, H-4A), 3.30 ,s, 3H, OCH3), 3.25 ,m, 1H,
H-5D), 2.09, 1.82 ,2s, 6H, C,O)CH3), 1.46 ,s, 3H, C,CH3)2),
1.41 ,d, 3H, H-6B), 1.40 ,s, 3H, C,CH3)2), 1.32 ,d, 3H,
J5,66.2 Hz, H-6A), and 1.20 ,d, 3H, J5,66.2 Hz, H-6C);
13C, d 171.1, 170.3, 165.8 ,3C, CvO), 138.7±127.3 ,Ph),
102.2 ,C-1D, JC,H161 Hz), 100.1 ,C-1A, JC,H170 Hz),
99.4 ,C,CH3)2), 99.3 ,C-1B, JC,H172 Hz), 97.8 ,C-1C,
JC,H170 Hz), 92.3 ,C-1E, JC,H169 Hz), 81.9 ,C-3E),
1
[a]D2288 ,c 1.0); NMR: H, d 7.36±7.21,m, 15H, Ph),
6.29 ,bd, 1H, JNH,26.6 Hz, NH), 4.86 ,d, 2H, J11.8 Hz,
OCH2), 4.75 ,d, 1H, J1,21.0 Hz, H-1A), 4.71,bs, 1H, H-1 C),
4.70±4.56 ,m, 5H, H-1D, OCH2), 4.07 ,dq, 1H, J4,59.6 Hz,
H-5C), 3.97±3.71,m, 7H, H-2 C, 3D, 3C, 2A, 3A, 6aD, 6bD), 3.70
,m, 1H, H-2D), 3.66 ,m, 1H, H-5A), 3.58 ,dd, 1H, H-4D), 3.38
,m, 2H, H-4A, 4C), 3.32 ,s, 3H, OCH3), 3.27 ,m, 2H, H-5D,
OH), 2.92 ,d, 1H, J4.7 Hz, OH), 2.06 ,s, 3H, C,O)CH3),
1.39, 1.38 ,2s, 6H, C,CH3)2), 1.31 ,d, 3H, J5,66.2 Hz, H-6A),
and 1.27 ,d, 3H, J5,66.2 Hz, H-6C); 13C, d 170.9 ,CvO),
139.1±127.3 ,Ph), 103.1 ,C-1D), 100.5 ,C-1C), 99.7 ,C-1A),
99.4 ,C,CH3)2), 80.9 ,C-4A), 80.6 ,C-4C), 79.4 ,C-3A), 77.9
,C-2A), 75.9 ,C-3D), 75.4, 75.6, 73.1,3C, OCH 2), 72.3
,C-4D), 72.0 ,C-3C), 71.1 ,C-2C), 67.9 ,C-5A), 67.5 ,C-5D),
67.4 ,C-5C), 61.8 ,C-6D), 57.5 ,C-2D), 54.7 ,OCH3), 29.6
,CCH3), 23.1,NHAc), 18.9 ,CCH 3), and 17.8, 17.6 ,2C,
C-6C, 6A); CIMS for C45H59NO14 ,M, 837.39) m/z838.4
,[M1H]2). Anal. Calcd for C45H59NO14: C, 64.50; H, 7.1 0;
N, 1.67%. Found: C, 64.50; H, 7.17; N, 1.61%.
p
3.3.11. Methyl -2,3,4,6-tetra-O-benzyl-a-d-glucopyrano-
syl)--1!3)--2-O-benzoyl-4-O-benzyl-a-l-rhamnopyrano-
syl)--1!3)--2-O-acetyl-4-O-benzyl-a-l-rhamnopyrano-
syl)--1!3)--2-acetamido-2-deoxy-4,6-O-isopropylidene-
b-d-glucopyranosyl)--1!2)-3,4-di-O-benzyl-a-l-rhamno-
pyranoside 25. p-Toluenesulphonic acid ,10 mg) was
added to a suspension of diol 24 ,950 mg, 1.07 mmol) in
MeCN ,8 mL) containing methyl orthoacetate ,550 mL,
4.3 mmol). The mixture was stirred for 45 min at rt. TLC
,solvent A, 19:1) showed that no starting material remained.
The reaction mixture was cooled to 08C, and 80% aq. AcOH
,1.5 mL) was added. After 30 min at rt, TLC ,solvent A,
19:1) showed that the intermediate orthoester had turned
into a more polar product. CH2Cl2 was added, and the
organic phase was washed with ice-water and satd aq.
NaCl, dried and evaporated to dryness to give 3 quantita-
80.8 ,C-4A), 79.8 ,C-4C), 79.6 ,C-4E ), 79.5 ,C-3A), 79.0
p
,C-2E), 77.9 ,C-3C), 77.8 ,C-3D), 77.5 ,C-4B ), 77.3
,C-2A), 76.2, 75.4, 75.3, 74.9, 73.1, 72.8 ,7C, OCH2), 72.7
,C-2C), 72.5 ,C-4D), 72.2 ,C-3B), 72.1,OCH 2), 70.1,C-5 E),
68.9 ,C-5B), 68.4 ,C-2B), 68.3 ,C-6E), 67.6 ,C-5A ), 67.5
p
p
,C-5C ), 67.4 ,C-5D), 62.2 ,C-6D), 57.8 ,C-2D), 54.5
,OCH3), 29.0 ,CCH3), 23.2, 21.0 ,C,O)CH3), 19.0
,CCH3), 17.8 ,C-6B), 17.7 ,C-6A), and 17.6 ,C-6C).
FABMS for C101H115NO25 ,M, 1741.78) m/z 1764.8
,[M1Na]1). Anal. Calcd for C101H115NO25: C, 69.60; H,
6.65; N, 0.80%. Found: C, 69.48; H, 6.81; N, 0.96%.
3.3.12. Methyl -2,3,4,6-tetra-O-benzyl-a-d-glucopyrano-
syl)--1!3)--2-O-benzoyl-4-O-benzyl-a-l-rhamnopyrano-
syl)--1!3)--2-O-acetyl-4-O-benzyl-a-l-rhamnopyranosyl)-
-1!3)--2-acetamido-2-deoxy-b-d-glucopyranosyl)--1!2)-
3,4-di-O-benzyl-a-l-rhamnopyranoside 26. 50% aq. TFA
,12 mL) was added, at 08C, to a solution of pentasaccharide
25 ,1.19 g, 683 mmol) in CH2Cl2 ,20 mL), and the biphasic
mixture was stirred vigorously at rt for 1h. Repeated
coevaporation with toluene and chromatography of the
residue ,solvent A, 193:7) provided diol 26 ,1.09 g, 94%)
as a white foam; [a]D1298 ,c 1.0); NMR: 1H, d 8.00±7.06
1
tively, as a white foam; NMR: H, d 7.40±7.27 ,m, 15H,
Ph), 5.74 ,bd, 1H, JNH,27.7 Hz, NH), 4.90 ,dd, 1H, J1,2
1.5 Hz, J2,33.3 Hz, H-2C), 4.86 ,d, 2H, J11.3 Hz, OCH2),
4.74±4.57 ,m, 5H, H-1D, OCH2), 4.65 ,bs, 2H, H-1A, 1C),
4.08 ,dd, 1H, J3,49.5 Hz, H-3C), 3.99 ,dq, 1H, J4,59.6 Hz,
H-5C), 3.92±3.84 ,m, 4H, H-2A, 3A, 6aD, 6bD), 3.70 ,m, 1H,
H-2D), 3.65 ,m, 1H, H-5A), 3.61,pt, 1H, J2,3J3,48.7 Hz,
H-3D), 3.55 ,dd, 1H, J4,58.9 Hz, H-4D), 3.36 ,pt, 1H,
H-4A), 3.35 ,pt, 1H, J3,4J4,59.5 Hz, H-4C), 3.30 ,s, 3H,
OCH3), 3.22 ,m, 1H, H-5D), 2.13, 1.83 ,2s, 6H, C,O)CH3),
1.47, 1.41 ,2s, 6H, C,CH3)2), 1.32 ,d, 3H, J5,66.2 Hz,
H-6A), and 1.27 ,d, 3H, J5,66.2 Hz, H-6C); 13C, d 171.6,
170.6 ,2C, CvO), 138.7±127.6 ,Ph), 102.8 ,C-1D), 99.9
,m, 45H, Ph), 5.69 ,bs, 1H, H-2B), 5.62 ,d, 1H, JNH,2
7.3 Hz, NH), 5.20 ,bs, 2H, H-1B, 1E), 5.00 ,bs, 1H, H-2C),
4.97±4.34 ,m, 18H, OCH2, H-1D, 1A, 1C), 4.31,dd, 1H,
J2,32.9 Hz, J1,29.4 Hz, H-3B), 4.22 ,d, 1H, J12.0 Hz,
OCH2), 4.15 ,dd, 1H, J2,33.2 Hz, J3,49.4 Hz, H-3C),
4.01,m, 2H, H-3 , 5E), 3.94±3.73 ,m, 6H, H-5C, 2A, 6aD,
E
p
p
,C-1A ), 99.5 ,C,CH3)2), 98.3 ,C-1C ), 81.3 ,C-4C), 80.9
,C-4A), 79.7 ,C-3A), 79.2 ,C-3D), 77.6 ,C-2A), 75.4, 74.8
,2C, OCH2), 73.6 ,C-2C), 73.2 ,OCH2), 72.4 ,C-4D), 69.5
3A, 5B, 6bD), 3.67 ,dd, 2H, H-4E, 4B), 3.59±3.40 ,m, 8H,
H-5A, 6aE, 3D, 2E, 2D, 4C, 6bE, 4D), 3.37 ,pt, 1H, J3,4
J4,59.4 Hz, H-4A), 3.30 ,s, 3H, OCH3), 3.28 ,m, 1H,