Gemini Surfactants with a Disaccharide Spacer
J. Am. Chem. Soc., Vol. 123, No. 5, 2001 883
Hz, C6, 2H), 3.33-3.26 (m, C6, 2H), 2.2-2.1 (m, R CH2, 4H), 2.07 (s,
C3 Ac, 6H), 2.06 (s, C4 Ac, 6H), 2.01 (s, C2 Ac, 6H), 1.59 (m, â CH2,
4H), 1.25 (m, alkyl chain, 32H), 0.88 (t, J ) 6.9 Hz, CH3, 6H).
13C NMR (100 MHz, CDCl3): δ 173.45, 170.42, 170.11, 170.03,
91.89, 70.38, 69.84, 69.43, 69.21, 38.90, 36.77, 32.11, 29.82, 29.71,
29.54, 25.67, 22.89, 20.88, 20.80, 14.33.
Hz, C1, 2H), 4.94-4.86 (m, C2 and C4, 4H), 3.86-3.82 (m, C5, 2H),
3.58-3.54 (m, C6, 2H), 3.33-3.26 (m, C6, 2H), 2.22-2.20 (m, R CH2,
4H), 2.09 (s, C3 Ac, 6H), 2.08 (s, C4 Ac, 6H), 2.03 (s, C2 Ac, 6H),
2.01 (m, CH2 R to CdC, 8H), 1.63 (m, â CH2, 4H), 1.27 (m, alkyl
chain, 40H), 0.89 (t, J ) 6.4 Hz, CH3, 6H).
FAB-HRMS (M + Li)+: Calcd for 1127.7182. Found: 1127.7137.
Anal. Calcd for C60H100N2O17 + 1/2 mol H2O: C 63.75, H 9.01, N
2.48. Found: C 63.55, H 8.93, N 2.44.
FAB-HRMS (M + Li)+: Calcd for 964.5695. Found: 964.5668.
Anal. Calcd for C48H80N2O17 + 1/2 mol H2O: C 59.67, H 8.45, N
2.90. Found: C 59.33, H 8.23, N 2.81.
General Procedure for Deacetylation under Ze´mplen condi-
tions.25,46 The fully protected surfactants were stirred in a solution of
50 mL of MeOH and 2 mL of 0.57 M NaOMe/MeOH at room
temperature overnight. Approximately 1.5 g of washed (acetone and
methanol) Dowex MR-3 mixed bed ion-exchange resin was added, and
the mixture stirred for 30 min, or until a pH of 7 was attained. The
neutralized solutions were filtered, the solvent removed under reduced
pressure, and the resulting solid dried in vacuo.
2,3,4,2′,3′,4′-Hexa-O-acetyl-6,6′-ditetradecanamido-6,6′-dideoxy-
r,r-D-trehalose, 4d. 3 (2.1 g, 3.2 mmol, 6.4 mmol equiv), 50 mL of
CH2Cl2, 2.4 mL of myristoyl chloride (9.0 mmol), and 2.3 g of PPh3
(8.8 mmol) in 10 mL of CH2Cl2 were reacted according to the general
procedure. Purification by column chromatography of the light yellow
syrup yielded 0.9 g (27%) 4d, mp 56-60 °C.
1H NMR (400 MHz, CDCl3): δ 5.71 (t, J ) 6 Hz, H on N, 2H),
5.46 (t, J ) 10 Hz, C3, 2H), 5.30 (d, J ) 4 Hz, C1, 2H), 4.92-4.84 (m,
C2 and C4, 4H), 3.84-3.81 (m, C5, 2H), 3.54-3.52 (m, C6, 2H), 3.30-
3.26 (m, C6, 2H), 2.20-2.15 (m, R CH2, 4H), 2.07 (s, C3 Ac, 6H),
2.07 (s, C4 Ac, 6H), 2.02 (s, C2 Ac, 6H) 1.59 (m, â CH2, 4H), 1.29-
1.24 (m, alkyl chain, 40H), 0.87 (t, J ) 6.4 Hz, CH3, 6H).
13C NMR (100 MHz, CDCl3): δ 173.52, 170.43, 170.13, 170.06,
91.89, 70.38, 69.84, 69.42, 69.21, 38.89, 36.77, 32.12, 29.86, 29.73,
29.56, 25.68, 22.89, 20.88, 20.79, 14.33.
6,6′-Dioctanamido-6,6′-dideoxy-r,r-D-trehalose, A-8. 4a (1.5 g)
was deacetylated as described above, to yield 1.0 g (95%) of A-8, mp
100-104 °C.
1H NMR (300 MHZ, CD3OD): δ 5.03 (d, J ) 3.3 Hz, C1, 2H),
3.85 (m, 2H), 3.74 (t, J ) 9.3 Hz, 2H), 3.45 (m, 6H), 3.12 (t, J ) 9.3
Hz, 2H), 2.20 (t, J ) 7.5 Hz, R CH2, 4H), 1.59 (m, â CH2, 4H), 1.30
(m, alkyl chain, 16H), 0.88 (t, J ) 6.6 Hz, CH3, 6H).
13C NMR (75 MHz, CD3OD): δ 177.23, 95.68, 74.28, 73.48, 73.26,
72.22, 41.44, 37.18, 33.05, 30.51, 30.32, 27.29, 23.87, 14.60.
FAB-HRMS (M + H)+: Calcd for 593.3661. Found: 593.3661.
Anal. Calcd for C28H52N2O11: C 56.74, H 8.84, N 4.73. Found: C
56.58, H 8.73, N 4.69.
FAB-HRMS (M + Li)+: Calcd for 1019.6243. Found: 1019.6274.
Anal. Calcd for C52H88N2O17: C 61.64, H 8.75, N 2.76. Found: C
61.69, H 8.86, N 2.64.
2,3,4,2′,3′,4′-Hexa-O-acetyl-6,6′-dihexadecanamido-6,6′-dideoxy-
r,r-D-trehalose, 4e. The reaction was carried out with 2.1 g (3.2 mmol,
6.4 mmol equiv) of 3, 50 mL of CH2Cl2, 2.7 mL (9.0 mmol) of
palmitoyl chloride, and 2.4 g (9.1 mmol) of PPh3 in 10 mL of CH2Cl2.
Column chromatography of the off-white, sticky solid afforded 2.9 g
(73%) of 4e as a white crystalline solid, mp 54-57 °C.
6,6′-Didecanamido-6,6′-dideoxy-r,r-D-trehalose, A-10. 4b (0.8 g)
was deacetylated to yield 0.6 g of (100%) A-10 as a crystalline solid,
mp 125-128 °C.
1H NMR (400 MHZ, CD3OD): δ 5.02 (d, J ) 4 Hz, C1, 2H), 3.86-
3.83 (m, 2H), 3.73 (t, J ) 8.8 Hz, 2H), 3.45-3.44 (m, 6H), 3.11 (t, J
) 8.8 Hz, 2H), 2.20 (t, J ) 6.8 Hz, R CH2, 4H), 1.59 (m, â CH2, 4H),
1.30 (m, alkyl chain, 24H), 0.88 (t, J ) 6.8 Hz, CH3, 6H).
13C NMR (100 MHz, CD3OD): δ 177.23, 95.69, 74.30, 73.49, 73.28,
72.23, 37.19, 33.22, 30.78, 30.66, 30.55, 27.30, 23.91, 14.62.
FAB-HRMS (M + Li)+: Calcd for 655.4357. Found: 655.4350.
Anal. Calcd for C32H60N2O11 + 1/2 mol H2O: C 58.43, H 9.35, N
4.26. Found: C 58.66, H 9.20, N 4.09.
1H NMR (400 MHz, CDCl3): 5.68 (t, J ) 6 Hz, H on N, 2H), 5.46
(t, J ) 9.6 Hz, C3, 2H), 5.30 (d, J ) 3.6 Hz, C1, 2H), 4.92-4.85 (m,
C2 and C4, 4H), 3.85-3.80 (m, C5, 2H), 3.57-3.52 (m, C6, 2H), 3.31-
3.26 (m, C6, 2H), 2.20-2.10 (m, R CH2, 4H), 2.07 (s, C3 Ac, 6H),
2.06 (s, C4 Ac, 6H), 2.01 (s, C2 Ac, 6H) 1.59 (m, â CH2, 4H), 1.29-
1.24 (m, alkyl chain, 48H), 0.87 (t, J ) 6.8 Hz, CH3, 6H).
13C NMR (100 MHz, CDCl3): δ 173.48, 170.43, 170.11, 170.04,
91.89, 70.38, 69.84, 69.42, 69.21, 38.90, 36.78, 32.12, 29.90, 29.73,
29.57, 25.68, 22.90, 20.88, 20.80, 14.33.
6,6′-Didodecanamido-6,6′-dideoxy-r,r-D-trehalose, A-12. Deacetyl-
ation of 4c under Ze´mplen conditions yielded 0.63 g (79%) of diamido
trehalose derivative A-12, mp 168-172 °C.
FAB-HRMS (M + Li)+: Calcd for 1075.6869. Found: 1075.6865.
(M + H)+: Calcd for 1069.6787. Found: 1069.6749
1H NMR (400 MHz, CD3OD): δ 5.03 (d, J ) 3.3 Hz, C1, 2H),
3.86-3.84 (m, 2H), 3.74 (t, J ) 9.2 Hz, 2H), 3.45-3.42 (m, 6H), 3.11
(t, J ) 10 Hz, 2H), 2.19 (t, J ) 7.6 Hz, R CH2, 4H), 1.59 (m, â CH2,
4H), 1.28 (m, alkyl chain, 32H), 0.88 (t, J ) 6.4 Hz, CH3, 6H).
13C NMR (100 MHz, CD3OD): δ 177.20, 95.66, 74.29, 73.48, 73.27,
72.21, 41.45, 37.18, 33.25, 30.96, 30.92, 30.81, 30.66, 30.56, 27.29,
23.91, 14.63.
Anal. Calcd for C56H92N2O17: C 62.90, H 9.05, N 2.62. Found: C
62.80, H 9.01, N 2.50.
2,3,4,2′,3′,4′-Hexa-O-acetyl-6,6′-dioctadecanamido-6,6′-dideoxy-
r,r-D-trehalose, 4f. According to the general procedure, 2.2 g (3.4
mmol, 6.8 mmol equiv) of 3, 50 mL of CH2Cl2, 1.9 mL (9.0 mmol) of
stearoyl chloride, and 2.29 g (8.7 mmol) of PPh3 in 10 mL of CH2Cl2
were reacted. 4f (1.9 g, 50%), mp 53-56 °C, was isolated by silica
gel chromatography of the sticky light orange solid.
FAB-HRMS (M + Li)+: Calcd for 711.4983. Found: 711.4952.
Anal. Calcd for C36H68N2O11: C 61.34, H 9.72, N 3.97. Found: C
61.21, H 9.67, N 3.90.
6,6′-Ditetradecanamido-6,6′-dideoxy-r,r-D-trehalose, A-14. Deace-
tylation of 0.9 g of 4d followed by drying in vacuo resulted in 0.6 g
(88%) of A-14, mp 174-179 °C.
1H NMR (400 MHz, CDCl3): δ 5.70 (t, J ) 6 Hz, H on N, 2H),
5.45 (t, J ) 9.9 Hz, C3, 2H), 5.29 (d, J ) 3.6 Hz, C1, 2H), 4.92-4.86
(m, C2 and C4, 4H), 3.82 (m, C5, 2H), 3.60-3.50 (m, C6, 2H), 3.33-
3.29 (m, C6, 2H), 2.18-2.16 (m, R CH2, 4H), 2.06 (s, C3 Ac, 6H),
2.06 (s, C4 Ac, 6H), 2.01 (s, C2 Ac, 6H) 1.59 (m, â CH2, 4H), 1.28-
1.24 (m, alkyl chain, 56H), 0.86 (t, J ) 6.4 Hz, CH3, 6H).
13C NMR (100 MHz, CDCl3): 173.43, 170.41, 170.09, 170.02, 91.87,
70.37, 69.83, 69.42, 69.21, 38.89, 36.76, 32.12, 29.89, 29.73, 29.56,
25.67, 22.88, 20.87, 20.79, 14.33.
1H NMR (400 MHz, CD3OD): δ 5.05 (d, J ) 3.6 Hz, C1, 2H),
3.86-3.83 (m, 2H), 3.73 (t, J ) 9.2 Hz, 2H), 3.45-3.41 (m, 6H), 3.11
(t, J ) 9.2 Hz, 2H), 2.19 (t, J ) 7.2 Hz, R CH2, 4H), 1.58 (m, â CH2,
4H), 1.27 (m, alkyl chain, 40H), 0.88 (t, J ) 6.8 Hz, CH3, 6H).
13C NMR (100 MHz, CD3OD): δ 177.22, 95.66, 74.30, 73.49, 73.29,
72.22, 41.46, 37.20, 33.26, 30.97, 30.83, 30.67, 30.57, 27.31, 23.92,
14.63.
FAB-HRMS (M + Li)+: Calcd for 767.5609. Found: 767.5609.
Anal. Calcd for C40H72N2O11: C 63.13, H 10.07, N 3.68. Found: C
63.00, H 10.06, N 3.55.
FAB-HRMS (M + Li)+: Calcd for 1131.7495. Found: 1131.7443.
Anal. Calcd for C60H104N2O17 + 1 mol H2O: C 63.02, H 9.34, N
2.45. Found: C 63.03, H 9.21, N 2.50.
2,3,4,2′,3′,4′-Hexa-O-acetyl-6,6′-di-(Z)-octadec-9-enamido-6,6′-
dideoxy-r,r-D-trehalose, 4g. 3 (2.0 g, 3.1 mmol, 6.2 mmol equiv),
50 mL of CH2Cl2, 2.98 mL (9.0 mmol) of oleoyl chloride, and 2.2 g
(0.4 mmol) of PPh3 in 10 mL of CH2Cl2 were reacted. Purification by
silica gel column chromatography afforded 0.8 g (23%) of 4g as a
hygroscopic, sticky solid, mp 50-56 °C.
6,6′-Dihexadecanamido-6,6′-dideoxy-r,r-D-trehalose, A-16. 4e
(2.9 g) was deprotected under Ze´mplen conditions to afford 1.8 g (86%)
of crystalline and hygroscopic A-16, mp 189-190 °C.
1H NMR (300 MHz, CDCl3): 5.66 (t, J ) 5.6 Hz, H on N, 2H),
5.48 (t, J ) 10 Hz C3, 2H), 5.36-5.34 (m, CdC, 4H), 5.32 (d, J ) 3.6
(46) Ze´mplen, G. Ber. Dtsch. Chem. Ges. 1927, 60, 1555.