C. M. Krell, D. Seebach
FULL PAPER
3037w, 2954w, 1750s, 1602w, 1498w, 1456w, 1379w, 1275m, 1166s,
O-Terminally Protected Tetramer 21: Acid 20 (308 mg, 0.348 mmol)
1105w, 1059w, 984w. – 1H NMR (400 MHz, CDCl3): δ ϭ 2.82–2.99 was deprotected in dioxane (8 mL) according to GP 4 in the pres-
[m, 8 H, C(O)CH2], 3.35 (d, J ϭ 6.0 Hz, 1 H, OH), 4.52–4.56 (m, ence of 10% Pd/C (30 mg) to yield the oligoacid 21 (249 mg, con-
3 H, HOCH, CH2CHϭCH2), 5.08–5.29 (m, 10 H, CHϭCH2, 4 ϫ taining 1.9 equiv. dioxane, quant.) as a colorless, hygroscopic
PhCH2), 5.52–5.58 (m, 3 H, OCHCH2), 5.78–5.88 (m, 1 H, CHϭ
glass. – RP-HPLC: tr ϭ 15.1 min, purity 97.5%. – pKa (25 °C):
t
CH2) 7.26–7.36 (m, 20 H, arom. H). – 13C NMR (100 MHz, 3.46. – [α]rD ϭ –17.3 (c ϭ 0.49, H2O; calcd. for solvent free com-
CDCl3): δ ϭ 35.44 (t), 35.47 (t), 35.80 (t), 38.68 (t), 65.80 (t), 67.30 pound). – IR (neat): 3479m, 2940m, 2595w, 1959w, 1740s, 1641w,
(d), 67.59 (t), 67.65 (t), 67.68 (t), 68.28 (d), 68.47 (d), 68.79 (d), 1377m, 1236m, 1169s, 1051m, 949w.
–
1H NMR (400 MHz,
118.75 (t), 128.26 (d), 128.33 (d), 128.45 (d), 128.52 (d), 128.55 (d),
128.58 (d), 128.64 (d), 128.66 (d), 131.61 (d), 134.88 (s), 134.93 (s),
135.15 (s), 167.87 (s), 167.94 (s), 167.99 (s), 168.11 (s), 168.17 (s),
CD3OD): δ ϭ 2.09 (s, 3 H, Me), 2.80–3.13 [m, 8 H, C(O)CH2],
4.95 (br. s, 5 H, CO2H), 5.41–5.51 (m, 4 H, OCHCH2) – 13C NMR
(100 MHz, CD3OD): δ ϭ 20.58 (q), 36.72 (t), 36.75 (t), 36.84 (t),
168.49 (s), 169.21 (s), 172.75 (s). – MS (MALDI): m/z ϭ 922 [M 69.59 (d), 69.93 (d), 69.97 (d), 70.41 (d), 170.04 (s), 170.06 (s),
ϩ K]ϩ, 906 [M ϩ Na]ϩ. – C47H46O17 (882.87): calcd. C 63.94,
H 5.25; found C 63.97, H 5.39.
170.17 (s), 171.55 (s), 171.64 (s), 171.91 (s), 171.98 (s), 172.19 (s),
172.78 (s). – MS (ESI–): m/z (%) ϭ 523 (100) [M – H]–, 365 (21),
249 (14); (ESIϩ): m/z (%) ϭ 547 (100) [M ϩ Na]ϩ. – HRMS
(ESI–, 4.7 T): m/z (C18H19O18–, [M – H]–) calcd. 523.0577; found
523.0573.
Tetramer Acetate 19: A solution of compound 18 (646 mg,
0.73 mmol) in CH2Cl2 (8 mL) was cooled to –10 °C and pyridine
(0.59 mL) was added. Acetyl chloride (0.078 mL, 1.1 mmol) was
added over 10 min before the solution was stirred at –10 °C for
45 min. The reaction mixture was poured on ice and extracted with
CH2Cl2 (3 ϫ). The organic layer was washed with 5% aq. citric
acid, sat. NaHCO3, and half sat. NaCl solutions, dried (Na2SO4),
and concentrated under reduced pressure. Purification by FC
(Et2O/CH2Cl2 3:97) yielded acetate 19 (654 mg, 97%) as a colorless
C-Terminally Protected Tetramer 22: Tetramer 18 (2.22 g,
2.51 mmol) was deprotected in dioxane (60 mL) according to GP
4 in the presence of 10% Pd/C (200 mg) to yield the oligoacid 22
(1.61 g, containing 1.5 equiv. dioxane, 98%) as a colorless, hygro-
scopic glass. – RP-HPLC: tr ϭ 24.2 min, purity 93.5% (3.5% of
tetramer 13). – IR (neat): 3468m, 2967w, 2600w, 1738s, 1639w,
1381w, 1173s, 1056m. – 1H NMR (400 MHz, CD3OD): δ ϭ 0.95
(t, J ϭ 7.4 Hz, 3 H, MeCH2), 1.66 (tq, J ϭ 6.6, 7.4 Hz, 2 H,
MeCH2), 2.74–3.08 [m, 8 H, C(O)CH2], 4.09 (t, J ϭ 6.6 Hz, 2 H,
CH2CH2O) 4.52–4.55 (m, 1 H, HOCH), 4.88 (br. s, 5 H, 4 ϫ
CO2H, HOCH), 5.44–5.51 (m, 3 H, OCHCH2) – 13C NMR
(100 MHz, CD3OD): δ ϭ 10.72 (q), 22.99 (t), 36.73 (t), 36.77 (t),
37.01 (t), 39.99 (t), 67.86 (t), 68.17 (d), 69.74 (d), 69.97 (d), 70.25
(d), 169.99 (s), 170.05 (s), 171.12 (s), 171.21 (s), 171.56 (s), 171.76
(s), 171.95 (s), 176.17 (s). – MS (ESI–): m/z (%) ϭ 523 (100) [M –
H]–, 407 (14), 389 (10), 291 (38), 249 (11); (ESIϩ): m/z (%) ϭ 547
[M ϩ Na]ϩ. – HRMS (ESI–, 4.7 T): m/z (C16H17O17–, [M – H]–)
calcd. 523.0941; found 523.0932.
t
oil. – Rf (Et2O/CH2Cl2 3:97) ϭ 0.23. – [α]rD ϭ –19.1 (c ϭ 1.0,
CHCl3). – IR (CHCl3): 3032w, 2952w, 1751s, 1499w, 1456w, 1378w,
1
1281w, 1166m, 1053w, 986w. – H NMR (500 MHz, CDCl3): δ ϭ
2.07 (s, 3 H, Me), 2.86–3.01 (m, 8 H, C(O)CH2), 4.53–4.55 (m, 2 H,
CH2CHϭCH2), 5.10–5.18 (m, 8 H, PhCH2), 5.19–5.29 (m, 2 H,
CHϭCH2) 5.50–5.57 (m, 4 H, OCHCH2), 5.79–5.87 (m, 1 H, CHϭ
CH2) 7.27–7.36 (m, 20 H, arom. H). – 13C NMR (125 MHz,
CDCl3): δ ϭ 20.44 (q), 35.42 (t), 35.46 (t), 35.57 (t), 35.76 (t), 65.76
(t), 67.40 (t), 67.55 (t), 67.57 (t), 67.63 (t), 67.95 (d), 68.38 (d), 68.41
(d), 68.74 (d), 118.73 (t), 128.18 (d), 128.22 (d), 128.24 (d), 128.29
(d), 128.36 (d), 128.43 (d), 128.51 (d), 128.54 (d), 128.57 (d), 128.58
(d), 128.62 (d), 128.64 (d), 131.58 (d), 134.86 (s), 134.89 (s), 134.93
(s), 135.07 (s), 167.76 (s), 167.83 (s), 167.92 (s), 168.05 (s), 168.11
(s), 168.42 (s), 168.53 (s), 169.93 (s). – MS (MALDI): m/z ϭ 948
[M ϩ Na]ϩ. – C49H48O18 (924.91): calcd. C 63.63, H 5.23; found
C 63.61, H 5.13.
Octamer 23: According to GP 1, acid 10 (162 mg, 0.150 mmol) was
converted into the acid chloride which was dissolved in CH2Cl2
(1.1 mL) and coupled according to GP 2 with 18 (132 mg,
0.150 mmol) in CH2Cl2 (0.5 mL) upon addition of the pyridine so-
lution within 40 min. Two FC (Et2O/CH2Cl2 1:30; first Et2O/hex-
ane 2:1, then Et2O/CH2Cl2 1:1) and recrystallization from boiling
(iPr)2O yielded 23 (39 mg, 13%) as a white solid. – M.p. 79.5–80.0
Tetramer Acid 20: Allyl ester 19 (651 mg, 0.704 mmol) was dis-
solved in THF (7 mL) and Pd(PPh3)4 (65 mg, 0.056 mmol) and im-
idazole (477 mg, 7.0 mmol) were added. The pale yellow solution
was stirred at room temp. for 2 h and then concentrated under re-
duced pressure (30 °C) to half of the initial volume. The solution
t
°C. – Rf (Et2O/CH2Cl2 1:30) ϭ 0.19. – [α]rD ϭ –20.2 (c ϭ 0.20,
was diluted with CH2Cl2 (30 mL), washed with 1 HCl (3 ϫ) and CHCl3). – IR (CHCl3): 3036w, 1752s, 1602w, 1498w, 1456w, 1377w,
1
half sat. NaCl solutions, dried (Na2SO4), and concentrated. The
resulting residue was dissolved in Et2O (5 mL), filtered through
Celite and purified by two FC (Et2O/hexane 2:1, 2% AcOH; Et2O/
toluene 1:5, 2% AcOH) to yield acid 20 (488 mg, 78%) as a yellow-
1280w, 1161m, 1112w, 1059w. – H NMR (500 MHz, CDCl3): δ ϭ
1.02 (s, 9 H, Me3C), 2.79–2.97 [m, 16 H, C(O)CH2], 4.52–4.53 (m,
2 H, CH2CHϭCH2) 4.55–4.57 (m, 1 H, SiOCH), 4.87 and 4.94
(AB, JAB ϭ 12.2 Hz, 2 H, PhCH2), 5.08–5.17 (m, 14 H, PhCH2),
ish, highly viscous glass. – Rf (Et2O/hexane 2:1, 2% AcOH) ϭ 0.15; 5.18–5.28 (m, 2 H, CHϭCH2), 5.45–5.47 (m, 1 H, OCHCH2), 5.49–
t
Rf (Et2O/toluene 1:5, 2% AcOH) ϭ 0.17. – [α]rD ϭ –21.4 (c ϭ 1.0,
5.53 (m, 6 H, OCHCH2), 5.78–5.86 (m, 1 H, CHϭCH2), 7.11–7.13
CHCl3). – IR (CHCl3): 3032w, 1752s, 1600w, 1498w, 1376w, 1165m, (m, 2 H, arom. H), 7.24–7.40 (m, 44 H, arom. H), 7.59–7.66 (m, 4
1
1056w. H NMR (400 MHz, CDCl3): δ ϭ 2.07 (s, 3 H, Me), 2.80–
H, arom. H). – 13C NMR (125 MHz, CDCl3): δ ϭ 19.34 (s), 26.78
3.02 [m, 8 H, C(O)CH2], 5.10–5.19 (m, 8 H, PhCH2), 5.50–5.60 (m, (q), 35.37 (t), 35.42 (t), 35.47 (t), 35.78 (t), 39.28 (t), 65.78 (t), 66.71
4 H, OCHCH2), 5.6–6.6 (br. s, 1 H, CO2H), 7.24–7.36 (m, 20 H, (t), 67.35 (t), 67.47 (t), 67.53 (t), 67.54 (t), 67.59 (t), 67.64 (t), 68.21
arom. H). – 13C NMR (100 MHz, CDCl3): δ ϭ 20.46 (q), 35.38 (t), (d), 68.42 (d), 68.76 (d), 69.28 (d), 118.76 (t), 127.50 (d), 127.64
35.44 (t), 35.58 (t), 35.61 (t), 67.57 (t), 67.65 (t), 67.68 (t), 67.72 (t),
(d), 128.14 (d), 128.22 (d), 128.24 (d), 128.27 (d), 128.31 (d), 128.36
68.00 (d), 68.57 (d), 68.63 (d), 128.23 (d), 128.26 (d), 128.32 (d), (d), 128.39 (d), 128.43 (d), 128.44 (d), 128.48 (d), 128.49 (d), 128.53
128.51 (d), 128.60 (d), 128.62 (d), 128.66 (d), 134.83 (s), 134.85 (s),
134.97 (s), 167.78 (s), 167.82 (s), 167.83 (s), 167.98 (s), 168.24 (s),
(d), 128.57 (d), 128.59 (d), 128.61 (d), 128.62 (d), 128.64 (d), 128.66
(d), 129.73 (d), 129.86 (d), 131.61 (d), 132.77 (s), 132.86 (s), 134.89
168.29 (s), 168.72 (s), 170.22 (s), 172.08 (s). – MS (MALDI): m/z ϭ (s), 134.92 (s), 134.95 (s), 134.99 (s), 135.01 (s), 135.05 (s), 135.18
929 [M – H ϩ 2 Na]ϩ, 907 [M ϩ Na]ϩ. – C46H44O18 (884.84): (s), 135.42 (s), 135.94 (d), 135.99 (d), 167.81 (s), 167.84 (s), 167.86
calcd. C 62.44, H 5.01; found C 62.20, H 5.08.
1216
(s), 167.91 (s), 167.94 (s), 167.95 (s), 168.00 (s), 168.07 (s), 168.16
Eur. J. Org. Chem. 2000, 1207Ϫ1218