906
A. Schäfer et al. / Tetrahedron: Asymmetry 20 (2009) 902–909
4.97–5.07 (m, 4H, 2 ꢃ CH2-Bn); 7.25–7.28 (m, 1OH, Ar). J2,3 = 1.0,
H-b-Thr); 5.05–5.24 (m, 4H, 2 ꢃ CH2-Bn); 5.44 (d, 1H, NH); 7.21–
7.37 (m, 6H, Ar); 7.59–7.64 (m, 4H, Ar). J1a,1e = 11.7, J1a,2 = 9.7,
0
0
J2,3 = 3.1, J3,3 = 5.1 Hz.
0
0
J1e,2 = 5.1, J2,3 = 6.6, J3,4 = 5.1, J4,5 = 1.5, J5,6 = 6.1, J5,6 = 7.9, J6.6 = 9.7,
4.6. (2S,3S)-Benzyl-1-benzyloxycarbonyl-3-methyl-aziridine-2-
JNH,H- -Thr = 9.7, JH- -Thr,H-b-Thr = 2.5, J
= 6.1 Hz. 13C NMR
a
a
H-b-Thr;CH3-Thr
carboxylate 15
(100 MHz, CDC13) d = 15.12 (1C, CH3-Thr); 18.21 (1C, C(CH3)3);
25.20 (1C, CH3); 25.73 (3C, t-Bu); 27.08 (1C, CH3); 58.04 (1C, C-
Procedure, workup and purification were similar as those de-
scribed for compound 14. Materials: Compound 13 (11.5 g,
26.5 mmol); chloroform (100 mL), methanol (25 mL), trifluoroace-
tic acid (50 mL). Yields of 15: 6.4 g, 74%; colourless oil;
a
-Thr); 61.63 (1C, C-6); 66.12 (1C, C-l); 66.16 (2C, 2 ꢃ CH2-Bn);
71.95 (1C, C-4); 72.36 (1C, C-b-Thr); 72.54 (1C, C-3); 75.27 (1C,
C-5); 77.15 (1C, C-2); 108.25 (1C, C(CH3)2); 126.57, 126.67,
127.09, 127.17, 127.43, 127.50, 127.52, 127.80, 128.65, 128.69,
132.34, 134.52, 134.60, 155.77 (24C, Ar); 155.77 (1C, CONH);
169.57 (1C, COOH). Maldi-Tof (DHB, positive mode) 768 (M+H)+,
790 (M+Na)+, 806 (M+K)+. Anal. Calcd for C44H53NO9Si: C, 68.81;
H, 6.96; N, 1.82. Found: C, 68.99; H, 7.01; N, 1.85.
½
a 2D0
ꢂ
¼ ꢀ67:1 (c 1, MeOH) [Ref. 26 ꢀ66.2]. 1H NMR (400 MHz,
CDCl3) d = 1.24 (d, 3H, CH3); 2.74 (dq, 1H, H-3); 3.14 (dd, 1H, H-
2); 5.03 (d, 1H, CH2a-Bn); 5.06 (d, 1H, CH2b-Bn); 7.26–7.29 (m,
10H, Ar). J2,3 = 6.6, J
= 5.6, JCH
= 12.2 Hz.
3;CH3
2-Bn
a
4.7. N -Benzyloxycarbonyl-3-O-[1,5-anhydro-6-O-tert-butyldi-
4.9. 3-O-[1,5-Anhydro-6-O-tert-butyldiphenylsilyl-3,4-O-iso
phenylsilyl-3,4-O-isopropylidene-
D
-galactitol-2]-
L-serine
propylidene-D-galactitol-2]-L-serine 18
benzylester 16
Compound 16 (325 mg, 0.43 mmol) was dissolved in dry meth-
anol (20 mL), Pd/C (10%, 70 mg) was added and the flask flushed
with hydrogen. After 48 h, the reaction was stopped by filtration.
Evaporation of the solvent yielded 18 (207 mg, 91%) colourless syr-
The anhydro alditol compound 7 (850 mg, 1.92 mmol) and the
aziridine derivative 14 (448 mg 1.44 mmol) were dissolved in dry
chloroform (10 mL). The solution was degassed and maintained
under high vacuum for 30 min. After flushing the flask with argon,
the resulting syrup was redissolved in dry chloroform (2 mL) and
treated with BF3ꢁEt2O (10% in chloroform, 5 drops). The yellow
solution was stirred for 16 h, treated with further 3 drops of cata-
lyst and stirred again for 16 h. After diluting with chloroform, sat-
urated sodium hydrogencarbonate was added, the organic phase
was dried over magnesium sulfate and filtered. Evaporation of
the solvent and column chromatography (petrol ether/ethyl ace-
tate 6:1) yielded compound 16 as a colourless syrup (586 mg,
up. ½a 2D0
ꢂ
¼ þ3:7 (c 0.5, MeOH). 1H NMR (400 MHz, DMSO-d6)
d = 1.01 (s, 9H, t-Bu); 1.30 (s, 3H, CH3); 1.45 (s, 3H, CH3); 3.11
(dd, 1H, H-la); 3.33 (dd, 1H, H-a-Ser); 3.83 (ddd, 1H, H-2); 3.73
(dd, 1H, H-6); 3.78 (dd, 1H, H-60); 3.83–3.88 (m, 3H, H-5, CH2-b-
Ser); 3.90 (dd, 1H, H-le); 4.13 (dd, 1H, H-3); 4.31 (dd, 1H, H-4);
7.45–7.50 (m, 6H, Ar); 7.66–7.69 (m, 4H, Ar). J1a,1e = 11.2,
J1a,2 = 10.2, J1e,2 = 5.6, J2,3 = 6.6, J3,4 = 5.6, J4,5 = 2.0, J5,6 = 6.6,
J5,6 = 6.6, J6,6 = 10.2, JH- -Ser,H -b-Ser = 4.6 Hz. 13C NMR (100 MHz,
0
0
0
a
DMSO-d6) d = 19.14 (1C, C(CH3)3); 26.41 (1C, CH3); 26.90 (3C, t-
Bu); 28.28 (1C, CH3); 54.80 (1C, C-a-Ser); 63.35 (1C, C-6); 65.80
(1C, C-l); 69.55 (1C, C-b-Ser); 73.15 (1C, C-4); 75.73 (1C, C-5);
76.43 (C-2); 77.49 (1C, C-3); 108.84 (1C, C(CH3)2); 128.21,
128.26, 130.25, 135.43, 135.46, (12C, Ar), 164.0 (lC,COOH). Maldi-
Tof (DHB, positive mode) 530 (M+H)+, 552 (M+Na)+, 568 (M+K)+.
54%). ½a 2D0
ꢂ
¼ þ9:7 (c 1, CH2C12). 1H NMR (500 MHz, CDC13)
d = 0.98 (s, 9H, t-Bu); 1.24 (s, 3H, CH3); 1.38 (s, 3H, CH3); 2.85
(dd, 1H, H-la); 3.33 (ddd, 1H, H-2); 3.55 (ddd, 1H, H-5); 3.60 (dd,
1H, H-3); 3.69 (dd, 1H, H-b-Ser); 3.75, 3.76 (2 ꢃ dd, 2 ꢃ 1H, CH2-
6); 3.78 (dd, 1H, H-le); 4.11 (dd, 1H, H-4); 4.17 (dd, 1H, H0-b-
Ser); 4.47 (ddd, 1H, H-
5.54 (d, 1H, NH); 7.22–7.35 (m, 16H, H-Ar); 7.59–7.63 (m, 4H, H-
a
-Ser); 5.02–5.24 (m, 4H, 2 ꢃ CH2-Bn);
4.10. 3-O-[1,5-Anhydro-6-O-tert-butyldiphenylsilyl-3,4-O-
Ar). J1a,1e = 11.4, J1a,2 = 10.4, J1e,2 = 5.7, J2,3 = 1.9, J3,4 = 6.3, J4,5 = 2.1,
isopropylidene-D-galactitol-2]-L-threonine 19
0
0
J5,6 = 6.0, J5,6 = 7.8, J6,6 = 9.8, JNH,H- -Ser = 8.8, JH- -Ser,H-b-Ser = 3.1,
a
a
JH- -Ser,H -b-Ser = 3.0, JH-b-Ser,H -b-Ser = 9.7 Hz. 13C NMR (100 MHz,
Compound 17 (720 mg, 0.94 mmol) was dissolved in dry meth-
anol (30 mL), Pd/C (10%, 150 mg) was added and the flask flushed
with hydrogen. After 48 h, the reaction was stopped by filtration.
Evaporation of the solvent gave 19 (481 mg, 95%) as a colourless
0
0
a
CDC13) d = 18.20 (1C, C(CH3)3); 25.15 (1C, CH3); 25.73 (3C, t-Bu);
27.07 (1C, CH3); 53.61 (1C, C-a-Ser); 61.68 (1C, C-6); 65.24 (1C,
C-l); 66.08, 66.19 (2 ꢃ 1C, 2 ꢃ CH2-Bn); 69.03 (1C, C-/3-Ser);
71.97 (1C, C-4); 75.26 (1C, C-5); 76.06 (1C, C-2); 76.88 (1C, C-3);
108.35 (1C, C(CH3)2); 126.57, 126.66, 127.11, 127.19, 127.38,
127.46, 127.51, 128.64, 128.68, 134.52, 134.59 (24C, Ar), 154.98
(1C, CONH), 169.07 (1C, CO). Maldi-Tof (DHB, positive mode) 754
(M+Na)+, 776 (M+Na)+, 793 (M+K)+. Anal. Calcd for C43H51NO9Si:
C, 68.50; H, 6.82; N, 1.86. Found: C, 68.31; H, 6.77; N, 1.71.
syrup. ½a 2D0
ꢂ
¼ ꢀ0:7 (c 0.5, MeOH). 1H NMR (400 MHz, MeOH-d4)
d = 0.94 (s, 9H, t-Bu); 1.24 (s, 3H, CH3); 1.25 (d, 3H, CH3-Thr);
1.41 (s, 3H, CH3); 3.07 (dd, 1H, H-la); 3.38 (dd, 1H, H-b-Thr);
3.58 (ddd, 1H, H-2); 3.67–3.76 (m, 3H, H-5, CH2-6); 3.80 (dd, 1H,
H-le); 4.07 (dd, 1H, H-3); 4.26 (dd, 1H, H-4); 4.35 (dd, 1H, H-
Thr); 7.27–7.37 (m, 6H, Ar); 7.56–7.63 (m, 4H, Ar). J1a,1e = 11.3,
J1a,2 = 9.8, J1e,2 = 5.4, J2,3 = 6.4, J3,4 = 5.9, J4,5 = 1.5, JNH,H- -Thr = 6.2,
a-
a
a
4.8. N -Benzyloxycarbonyl-3-O-[1,5-anhydro-6-O-tert-butyldi-
JH- -Thr,H-b-Thr = 4.6, JH-b-Thr;CH
a
= 5.0 Hz. 13C NMR (100 MHz,
3-Thr
phenylsilyl-3,4-O-isopropylidene-
benzylester 17
D
-galactitol-2]-
L-threonine
MeOH-d4) d 15.43 (1C, CH3-Thr); 18.45 (1C, C(CH3)3); 25.18 (1C,
CH3); 26.11 (3C, t-Bu); 27.16 (1C, CH3); 59.86 (1C, C-b-Thr);
63.21 (1C, C-6); 66.56 (1C, C-l); 72.04 (C-a-Thr); 73.53 (1C, C-4);
The reaction conditions, workup and purification were similar
to those described for the synthesis of 16. Materials: Compound
7 (1.5 g, 339 mmol), aziridine derivative 15 (735 mg, 2.26 mmol),
chloroform (2 mL), BF3ꢁEt2O as above. The eluent used for flash
chromatography was petrol ether/ethyl acetate 8:1. The product
74.12 (1C, C-2); 76.51 (1C, C-5); 77.90 (1C, C-3); 127.63, 127.68,
129.80, 135.57, 135.61 (12 C, Ar); 190.05 (lC,COOH). Maldi-Tof
(DHB, positive mode) 544 (M+H)+, 566 (M+Na)+, 582 (M+K)+.
4.11. 30-O-[1,5-Anhydro-
D-galactitol-2]-L-serine trifluoroacetate
20
17 (740 mg, 44%) was obtained as a colourless syrup. ½a D20
ꢂ
¼ þ0:4
(c 1, CH2C12); 1H NMR (400 MHz, CDC13) d = 0.98 (s, 9H, t-Bu);
1.11 (d, 3H, CH3-Thr); 1.22 (s, 3H, CH3); 1.38 (s, 3H, CH3); 2.76
(dd, 1H, H-la); 3.39 (dd, 1H, H-3); 3.41 (dd, 1H, H-2); 3.49 (ddd,
1H, H-5); 3.66 (dd, 1H, H-le); 3.72, 3.74 (2 ꢃ dd, 2 ꢃ 1H, CH2-6);
A solution of compound 18 (150 mg, 0.28 mmol) in trifluoroace-
tic acid (95%, 1 mL) was stirred for 1 h. The trifluoroacetic acid was
evaporated, the residue was dissolved in water and the solvent was
4.03 (dd, 1H, H-4); 4.31 (dd, 1H, H-
a-Thr); 4.43 (dd, 1H,
removed to give 20 (88 mg, 86%) as a colourless solid. ½a D20
¼ þ17:4
ꢂ