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B. Romagnoli et al. / Tetrahedron 59 (2003) 3975–3988
NMR (250 MHz, d6-DMSO) d 1.32 (36H, s, (CH3)3C), 3.25
(12H, bm, –OCONHCH2–), 4.98 (2H, bm, –CHOCO),
5.25 (1H0, bm, –CHOH), 7.03 (4H, bm, –OCONH–), 7.98
(8H, AA XX0, H-Ar), 8.70 (H, bm, –CONH–); 13C NMR
(62.5 MHz, d6-DMSO) d 28.7, 40.5, 43.5, 69.9, 73.6,
80.1, 127.6, 130.3, 132.9, 138.2, 156.9, 165.6, 168.3; IR n
3339, 1716, 1686 cm21; MALDI-TOF MS calcd for
C45H66O15N6: 930.65, (Mþ); obsd: 953.97 (MþNa)þ,
969.95 (MþK)þ.
chromatography (CHCl3/EtOH, 88:12) afforded 8 as a white
solid (0.39 g, 65%. Mp 245–247 8C. TLC Rf 0.6 (CHCl3/
EtOH, 88:12). 1H NMR (250 MHz, d6-DMSO) d 1.35 (72H,
s, (CH3)3C), 3.25 (16H, bm, –OCONHCH2–), 3.68
(12H, bm, –CONHCH2–), 5.01 (4H, bm, –CHOCO),
5.20 (1H, bm, –CHOH), 5.46 (2H, bm, –CHOCO–), 7.05
(8H, bm, –OCONH–), 8.01 (28H, AA0XX0, H-Ar), 8.73
(2H, bm, –CONH–), 8.97 (4H, bm, –CONH–); 13C NMR
(62.5 MHz, d6-DMSO) d 28.5, 40.8, 43.5, 72.6, 72.9, 73.5,
78.2, 127.5, 127.7, 129.7, 129.8, 132.6, 132.8, 138.5, 138.7,
156.1, 165.2, 165.4, 166.0, 166.3; IR n 3323, 1704,
1680 cm21; MALDI-TOF MS: calcd for C109H146O35N14:
2211.01 (Mþ); obsd; 2234.03 (MþNa)þ.
4.2.5. Second generation dendron [G-2]-ArCHO (6).
Employing an identical procedure used to produce [G-1]-
ArCHO 6, the second generation dendron [G-2]-ArCHO 6
was obtained as a white solid (0.108 g, 74%) from [G-2]-OH
2 (0.12 g, 0.13 mmol), 4-carboxybenzaldehyde (0.02 g,
0.13 mmol), dry THF (2 mL), DCC (0.03 g, 0.13 mmol)
and DMAP (catalytic amount). Mp 233–2358C. TLC Rf 0.6
(CH2Cl2/EtOH, 9:1). 1H NMR (250 MHz, d6-DMSO) d
1.35 (36H, s, (CH3)3C–), 3.27 (8H, bm, –OCONHCH2–),
3.74 (4H, bm, –CONHCH2–), 5.01 (2H, bm, –CHOCO–),
5.50 (1H, bm, –CHOCO–), 7.07 (4H, bm, –OCONH–),
7.93 (2H, AA0XX0, H-Ar), 8.07 (8H, AA0XX0, H-Ar), 8.21
(2H, AA0XX0, H-Ar), 8.98 (2H, bm, –CONH–); 10.16 (1H,
s, CHO); 13C NMR (62.5 MHz, d6-DMSO) d 28.1, 40.7,
43.5, 72.9, 73.3, 77.8, 127.1, 129.4, 129.5, 130.0, 132.4,
134.8, 138.1, 139.0, 156.8, 164.9, 165.1, 166.0, 192.1; IR n
3340, 1720, 1708, 1626 cm21; MALDI-TOF MS: calcd for
C53H70O17N6: 1062.78 (Mþ); obsd: 1086.52 (MþNa)þ,
1102.43 (MþK)þ.
4.2.8. Third generation dendron [G-3]-ArCHO (9).
Employing an identical procedure used to produce [G-1]-
ArCHO 4, the third generation dendron [G-3]-ArCHO 9 was
obtained as a white solid (0.24 g, 73%) from [G-3]-OH 8
(0.30 g, 0.14 mmol), 4-carboxybenzaldehyde (0.02 g, 0.14
m mol) dry THF (3 mL), DCC (0.03 g, 0.14 mmol) and
DMAP (catalytic amount). Mp 236–2658C. TLC Rf 0.7
(CHCl3/EtOH, 9:1). 1H NMR (250 MHz, d6-DMSO) d 1.35
(72H, s, (CH3)3C), 3.27 (16H, bm, –OCONHCH2–), 3.75
(12H, bm, –CONHCH2–), 5.01 (4H, bm, –CHOCO), 5.50
(3H, bm, –CHOCO), 7.06 (8H, bm, –OCONH–), 7.93
(12H, AA0XX0, H-Ar), 8.08 (14H, AA0XX0, H-Ar), 8.09
(2H, AA0XX0, H-Ar), 8.97 (2H, bm, –CONH–), 10.16
(1H, s, CHO); 13C NMR (62.5 MHz, d6-DMSO) d 28.4,
40.70, 42.3, 43.5, 72.9, 73.4, 73.9, 79.5, 127.0, 127.4, 127.6,
129.5, 129.8, 130.4, 132.6, 132.8, 135.0, 138.4, 138.6,
139.4, 156.1, 165.2, 165.4, 165.8, 166.3, 193.3, IR n 3338,
1718, 1708, 1655 cm21; MALDI-TOF MS: calcd for
C117H150O37N14: 2343.03 (Mþ); obsd; 2366.13 (MþNa)þ,
2382.02 (MþK)þ.
4.2.6. Second generation dendron [G-2]-ArCO2H (7). A
solution of 6 (0.50 g, 0.47 mmol) and pyridinium dichro-
mate (PDC) (0.47 g, 1.25 mmol) in dry DMF (5 mL) was
stirred at room temperature for 48 h. Water (10 mL) was
added to the mixture and the aqueous phase was extracted
with EtOAc (2£10 mL). The combined organic phases were
washed with 1M HCl (10 mL) and brine (10 mL). The
organic solution was dried over Na2SO4, filtered and then
concentrated in vacuo to afford a cream solid that was
purified by column chromatography (CH2Cl2/EtOH, 95:5).
The pure product 7 was isolated as a white solid
(0.28 g, 55%). Mp 236–2388C. TLC Rf 0.5 (CH2Cl2/
EtOH, 85:15). 1H NMR (250 MHz, d6-DMSO) d 1.23 (36H,
s, (CH3)3C), 3.16 (8H, bm, –OCONHCH2–), 3.59 (4H, bm,
–CONHCH2–), 4.90 (2H, bm, –CHOCO), 5.35 (1H, bm,
–CHOCO–), 6.95 (4H, bm, –OCONH–), 7.86 (12H,
AA0XX0, H-Ar), 8.92 (2H, bm, –CONH–); 13C NMR
(62.5 MHz, d6-DMSO) d 27.3, 39.2, 39.9, 71.0, 72.1, 78.7,
126.5, 128.4, 128.6, 129.3, 131.5, 131.9, 132.0, 136.5,
156.3, 164.1, 164.7, 166.5, 167.1; IR n 3323, 1704,
1680 cm21; MALDI-TOF MS: calcd for C53H70O18N6:
1078.78 (Mþ); obsd: 1102.23 (MþNa)þ.
4.2.9. Third generation dendron [G-3]-ArCO2H (10).
Employing an identical procedure used to produce [G-2]-
ArCO2H 7, the third generation dendron [G-3]-ArCO2H 10
was obtained as a white solid (0.060 g, 49%) from [G-3]-
ArCHO 9 (0.13 g, 0.06 mmol), PDC (0.80 g, 0.21 mmol)
and DMF (1 mL). Mp 230–232 8C. TLC Rf 0.5 (CHCl3/
EtOH, 85:15). 1H NMR (250 MHz, d6-DMSO) d 1.28 (72H,
s, (CH3)3C), 3.21 (16H, bm, –OCONHCH2–), 3.67 (12H,
bm, –CONHCH2–), 4.95 (4H, bm, –CH–), 5.40 (3H, bm,
–CH–), 7.00 (8H, bm, –OCONH–), 7.87 (28H, AA0XX0,
H-Ar), 8.91 (6H, bm, –CONH–); 13C NMR (100.1 MHz,
d6-DMSO) d 28.1, 40.6, 41.2, 43.5, 72.5, 73.2, 73.5, 77.8,
127.1, 127.3, 127.5, 129.1, 129.4, 129.5, 132.3, 132.4,
132.5, 138.1, 138.3, 138.4, 155.8, 164.8, 164.9, 165.0,
165.1, 166.0, 167.5; IR n 3343, 1725, 1720, 1650 cm21
;
MALDI-TOF MS: calcd for C117H150O38N14: 2359.02
(Mþ); obsd; 2382.13 (MþNa)þ, 2398.02 (MþK)þ.
4.2.7. Third generation dendron [G-3]-OH (8). 1-Benzo-
triazolyloxy-tris-(dimethylamino)-phosphonium hexafluoro-
phosphane (BOP) (0.161 g, 0.36 mmol) was added under
nitrogen to a solution of 7 (0.39 g, 0.36 mmol), 1,3-diamino-
2-hydroxypropane (0.16 g, 0.18 mmol), and freshly distilled
triethylamine (0.1 mL, 0.72 mmol) in dry CH3CN (3 mL).
The mixture was stirred for 12 h at room temperature and
brine (10 mL) was added. The aqueous phase was extracted
with EtOAc (2£30 mL) and the combined organic phase
wee dried over Na2SO4, and evaporated in vacuo. Column
4.2.10. First generation dendrimer [G-1]3-N (12).
BOP (0.300 g, 0.56 mmol) was added to a solution of 5
(0.30 g, 0.68 mmol), tris-(2-ethylamino)amine (0.03 mL),
0.22 mmol) and triethylamine (0.2 mL, 1.44 mmol) in dry
CH3CN (5 mL) under nitrogen. The mixture was stirred for
2 days at room temperature and then water (20 mL) was
added. The aqueous phase was extracted with CHCl3
(3£20 mL) and the combined organic phase were dried
over Na2SO4. The solution was filtered and then concen-
trated in vacuo to yield the crude product. Column