Dendritic Macromolecules
5618 5626
(OC-CH3), 26.82 (-C-(CH3)3), 29.14, 30.62 (succ. -CH2-), 62.12, 69.28
(glycerol, -CH2-), 127.71, 130.09, 131.65, 135.27 (arom. CH), 170.52,
171.19, 171.58 ppm ( -C(=O)-); FAB-MS: m/z calcd: 514.6 [M]+ ; found:
515.4 [M+H]+ ; elemental analysis calcd (%): C 63.01, H 6.66; found: C
62.76, H 6.69; SEC: Mw =547, Mn =528, PDI=1.04.
[M]+ ; found: 947.9 [M+H]+ ; elemental analysis calcd (%):C 57.07, H
6.17; found: C 57.15, H 6.26; SEC: Mw =1075, Mn =1041, PDI=1.03.
bzld-[G3]-PGLSA-TBDPS (8): Dendron 8 was synthesized by two meth-
ods, first by coupling dendron 6 to dendron 4 convergently, and second
by coupling compound 2 to dendron 7 divergently.
bzld-[G2]-PGLSA-TBDPS (5): Compound 4 (1.90 g, 4.41 mmol) was stir-
red in CH2Cl2 (100 mL) with DPTS (1.30 g, 4.41 mmol), compound 2
(2.72 g, 9.70 mmol), and DCC (2.00 g, 9.70 mmol). The solution was stir-
red for 18 h. The DCU precipitate was filtered and the solvent was
evaporated. A solution of 1:1 hexanes/EtOAc was added and impurities
precipitated. The solution was filtered, concentrated and further purified
by column chromatography (1:1 hexanes/EtOAc) to afford 3.70 g of
product (88% yield). Rf =0.22 (1:1 hexanes/EtOAc); 1H NMR (CDCl3):
d=1.08 (s, 9H; tBu), 2.57 2.79 (m, 12H; -CH2-CH2), 4.08 4.14, 4.16 4.22
(m, 12H; -CH2-CH-CH2-), 4.70 4.71 (m, 2H; -CH2-CH-CH2-), 5.21 (m,
1H; CH), 5.49 5.54 (m, 1H; CH), 7.32 7.41, 7.47 7.49, 7.62 7.67 ppm
(m, 20H; arom. bzld and phenyl CH); 13C NMR (CDCl3): d=19.31 (-C-
(CH3)3), 27.04 (-C-(CH3)3), 28.98, 29.33, 30.81 (succ. -CH2-), 62.48, 66.50,
69.16, 69.43 (glycerol, -CH2-), 101.33 (O-CH-O), 126.22, 127.95, 128.49,
129.26, 130.32, 131.92, 135.49 (arom. CH), 138.02 (arom. bzld -C-),
Convergent synthesis: Compound 6 (1.05 g, 1.47 mmol) was stirred in
CH2Cl2 (75 mL), and compound 4 (0.29 g, 0.67 mmol), DPTS (0.20 g,
0.67 mmol), and DCC (0.41 g, 2.00 mmol) were added. The solution was
stirred for 48 h. The DCU precipitate was filtered and the solvent was
evaporated. The product was purified by column chromatography (3:7
hexanes/EtOAc) to afford 0.99 g of product (82% yield).
Divergent synthesis: Compound
7 (0.55 g, 0.71 mmol) was stirred in
CH2Cl2 (50 mL), and DPTS (0.42 g, 1.41 mmol), compound 2 (0.87 g,
3.11 mmol), and DCC (0.64 g, 3.12 mmol) were added. The solution was
stirred for 18 h. The DCU precipitate was filtered and the solvent was
evaporated. The product was purified by column chromatography (3:7
hexanes/EtOAc) to afford 0.71 g of product (54% yield). Rf =0.08 (3:7
hexanes/EtOAc); 1H NMR (CDCl3): d=1.08 (s, 9H; tBu), 2.54 2.92 (m,
28H; -CH2-CH2), 4.08 4.15, 4.22 4.27 (m, 28H; -CH2-CH-CH2-), 4.71 (s,
4H; -CH2-CH-CH2-), 5.21 5.24 (m, 3H; CH), 5.52 (s, 4H; CH), 7.31
7.42, 7.45 7.49, 7.65 7.67 ppm (m, 30H; arom. bzld and phenyl CH); 13C
NMR (CDCl3): d=19.31 (-C-(CH3)3), 27.04 (-C-(CH3)3), 29.35, 30.81
(succ. -CH2-), 62.49, 66.53, 69.16, 69.47 (glycerol, -CH2-), 101.33 (O-CH-
O), 126.21, 127.94, 128.48, 129.26, 130.32, 135.47 (arom. CH), 138.02
(arom. bzld -C-), 171.90, 172.28 ppm (succ. -C(=O)-); GC-MS: m/z calcd:
1827.9 [M]+ ; found: 1825.6 [MꢀH]+ ; HR-FAB: m/z calcd: 1826.6233
[M]+ ; found: 1825.6124 [MꢀH]+ ; elemental analysis calcd (%):C 61.11,
H 5.85; found: C 60.66, H 5.85; SEC: Mw =1830, Mn =1810, PDI=1.01.
171.93, 172.28 ppm (succ. -C(=O)-); GC-MS: m/z calcd: 954.4 [M]+
;
found: 955.3 [M+H]+ ; elemental analysis calcd (%): C 64.14, H 6.12;
found: C 64.35, H 6.29; SEC: Mw =940, Mn =930, PDI=1.01.
bzld-[G2]-PGLSA-acid (6): Compound 5 (1.00 g, 1.04 mmol) was dis-
solved in THF (75 mL). Next, tetrabutylammonium fluoride trihydrate
(1.25 g, 3.96 mmol) was added to the solution and it was stirred for 1
hour, after which the reaction was complete as indicated by TLC. The
solution was diluted with H2O (25 mL) and acidified with 1n HCl to pH
3. The product was extracted into CH2Cl2, dried over Na2SO4, concentrat-
ed, and dried on the vacuum line. The product was purified by column
chromatography (0 5% MeOH in CH2Cl2) for 0.65 g of product (87%
bzld-[G3]-PGLSA-acid (9): Compound 8 (2.00 g, 1.09 mmol) was dis-
solved in THF (125 mL). Next, tetrabutylammonium fluoride trihydrate
(1.3 g, 4.1 mmol) was added to the solution. The mixture was stirred for
1 hour, after which the reaction was complete as indicated by TLC. The
solution was diluted with H2O (25 mL) and acidified with 1n HCl to pH
3. The product was extracted into CH2Cl2, dried over Na2SO4, concentrat-
ed, and dried on the vacuum line. The product was purified by column
chromatography (0 5% MeOH in CH2Cl2) to afford 1.44 g of product
(83% yield). Rf =0.21 (5% MeOH in CH2Cl2); 1H NMR (CDCl3): d=
2.58 2.75 (m, 28H; -CH2-CH2), 4.11 4.16, 4.19 4.27 (m, 28H; -CH2-CH-
CH2-), 4.71 4.72 (m, 4H; -CH2-CH-CH2-), 5.21 5.28 (m, 3H; CH), 5.52
5.53 (m, 4H; CH), 7.32 7.37, 7.46 7.49 ppm (m, 20H; arom. bzld CH);
13C NMR (CDCl3): d=29.05, 29.36 (succ. -CH2-), 62.51, 66.58, 69.16
(glycerol, -CH2-), 101.36 (O-CH-O), 126.21, 128.49, 129.29 (arom. CH),
137.95 (arom. bzld -C-), 171.83, 173.01 ppm (succ. -C(=O)-); GC-MS: m/z
calcd: 1588.5 [M]+ ; found: 1587.5 [MꢀH]+ ; elemental analysis calcd
(%):C 58.18, H 5.58; found: C 58.02, H 5.60; SEC: Mw =1650, Mn =1620,
PDI=1.02.
1
yield). Rf =0.24 (5% MeOH in CH2Cl2). H NMR (CDCl3): d=2.55 2.77
(m, 12H; -CH2-CH2), 4.10 4.17, 4.24 4.31 (m, 12H; -CH2-CH-CH2-),
4.74 4.75 (m, 2H; -CH2-CH-CH2-), 5.28 5.31 (m, 1H; CH), 5.52 5.54 (m,
2H; CH), 7.33 7.38, 7.47 7.49 ppm (m, 10H; arom. bzld CH); 13C NMR
(CDCl3): d=28.72, 29.03, 29.38 (succ. -CH2-), 62.68, 66.56, 69.16 (glycer-
ol, -CH2-), 101.44 (O-CH-O), 126.23, 128.50, 129.33 (arom. CH), 137.75
(arom. bzld -C-), 172.67, 175.16 (succ. -C(=O)-); GC-MS: m/z calcd:
716.2 [M]+ ; found: 715.2 [MꢀH]ꢀ; elemental analysis calcd (%):C 58.66,
H 5.63; found: C 58.71, H 5.82; SEC: Mw =810, Mn =800, PDI=1.01.
HO-[G2]-PGLSA-TBDPS (7): Compound 5 (1.55 g, 1.62 mmol) was dis-
solved in THF (40 mL) and 20% Pd(OH)2/C (1.0 g) was added. The solu-
tion was then placed in a Parr tube on a hydrogenator and shaken under
50 psi H2 for 4 h. The solution was then filtered over wet Celite, concen-
trated, and purified by column chromatography (0 25% acetone in
EtOAc) to yield 1.12 g of product (95% yield). Rf =0.25 (1:3 acetone/
EtOAc). 1H NMR (CDCl3): d=1.07 (s, 9H; tBu), 2.25 (brs, 4H; -OH),
2.58 2.82 (m, 12H; -CH2-CH2), 3.71 3.74, 4.09 4.26 (m, 12H; -CH2-CH-
CH2-), 4.87 4.99, 5.24 5.25 (m, 3H; -CH2-CH-CH2-), 7.34 7.43, 7.63 7.68
ppm (m, 10H; phenyl CH); 13C NMR (CDCl3): d=14.52 (-C-(CH3)3),
25.78 (-C-(CH3)3), 26.99, 29.30, 30.51, 30.81 (succ. -CH2-), 62.08, 63.44,
68.17, 70.23 (glycerol, -CH2-), 125.71, 127.96, 130.35, 135.45 (phenyl),
171.94, 172.40 (succ. -C(=O)-); GC-MS: m/z calcd: 778.3 [M]+ ; found
779.5 [M+H]+ ; SEC: Mw =800, Mn =792, PDI=1.01
HO-[G3]-PGLSA-TBDPS (10): Compound 8 (0.53 g, 0.29 mmol) was
dissolved in THF (50 mL) in a Parr tube. 20% Pd(OH)2/C (0.4 g) was
added and the flask was evacuated and filled with 50 psi of H2. The mix-
ture was shaken for 8 h, then filtered over wet Celite. The filtrate was
dried to produce a clear oil, which was purified by column chromatogra-
phy (0 50% acetone in EtOAc) to afford 0.38 g of product (88% yield).
Rf =0.23 (1:1 acetone/EtOAc); 1H NMR (CDCl3): d=1.3 (s, 9H; tBu),
2.52 2.86 (m, 28H; -CH2-CH2), 3.44 3.94 (m, 24, -CH2-CH-CH2- and
-OH), 4.10 4.38, (m, 12H; -CH2-CH-CH2-), 4.82 4.92 (m, 4H; CH),
5.18 5.30 (m, 3H; CH), 7.28 7.43, 7.50 7.54, 7.60 7.66 ppm (m, 10H;
phenyl CH); 13C NMR (CDCl3): d=19.04 (-C-(CH3)3), 24.44 (-C-(CH3)3),
26.76, 27.12, 28.82, 28.97, 29.10, 30.57 (succ. -CH2-), 61.17, 62.33, 63.21,
69.30, 75.52 (glycerol, -CH2-), 127.72, 130.11, 131.57, 134.36, 135.20
(arom. CH), 171.66, 171.72, 171.99, 172.27, 172.38, 172.46 ppm (succ.
-C(=O)-); MALDI-MS: m/z calcd: 1475.5 [M]+ ; found: 1475.56 [M+H]+
; SEC: Mw =2101, Mn =1994, PDI=1.05.
Acetyl derivative of compound 7: Compound 7 was a hydroscopic oil and
repeated attempts to obtain satisfactory elemental analysis failed. Thus,
we decided to prepare the acetyl analogue. Compound 7 (0.55 g, 0.70
mmol) was stirred in CH2Cl2 (40 mL) with DPTS (0.39 g, 1.34 mmol),
freshly distilled acetic acid (0.19 mL, 3.36 mmol), and DCC (0.87 g, 4.20
mmol). The solution was stirred for 18 h. The DCU precipitate was fil-
tered and the solvent was evaporated. The residue was resuspended in a
minimum of CH2Cl2, cooled to 108C and filtered. The resulting solution
was concentrated and further purified by column chromatography (0 5%
acetone in CH2Cl2) to afford 0.49 g of product (66% yield). Rf =0.17
Acetyl derivative of compound 10: Compound 10 was a hydroscopic oil
and repeated attempts to obtain satisfactory elemental analysis failed.
Thus, we decided to prepare the acetyl analogue. Compound 10 (0.24 g,
0.16 mmol) was stirred in CH2Cl2 (40 mL) with DPTS (0.19 g, 0.65
mmol), freshly distilled acetic acid (0.09 mL, 1.55 mmol), and DCC (0.40
g, 1.94 mmol). The solution was stirred for 18 h. The DCU precipitate
was filtered and the solvent was evaporated. The residue was resuspend-
ed in a minimum of CH2Cl2, cooled to 108C and filtered. The resulting
1
(5% acetone in CH2Cl2); H NMR (CDCl3): d=1.07 (s, 9H; tBu), 2.04 (s,
12H; -CH3), 2.55 2.83 (m, 12H; -CH2-CH2), 4.09 4.32 (m, 12H; -CH2-
CH-CH2-), 5.20 5.29 (m, 3H; -CH2-CH-CH2-), 7.32 7.44, 7.61 7.67 ppm
(m, 10H; phenyl CH); 13C NMR (CDCl3): d=19.10 (-C-(CH3)3), 20.67
(OC-CH3), 26.82 (-C-(CH3)3), 28.60, 28.80, 29.10, 30.59 (succ. -CH2-),
62.11, 62.31, 69.39 (glycerol, -CH2-), 127.72, 130.09, 131.67, 135.27 (arom.
CH), 170.50, 171.33, 171.61 ppm ( -C(=O)-); FAB-MS: m/z calcd: 947.0
5623
Chem. Eur. J. 2003, 9, 5618 5626
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim