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M. Martinkovaꢀ et al. / Tetrahedron 63 (2007) 10603–10607
added brine (20 mL) and the solution was extracted with
ethyl acetate (2ꢂ25 mL). The combined organic layers
were dried (Na2SO4) and solvent was evaporated under
reduced pressure. Chromatography of residue on silica gel
(hexane–ethyl acetate, 1:1) afforded 0.31 g (84%) of lactol
20.8 (CH3), 52.5 (CH3), 60.8 (CH2), 61.5 (CH2), 62.4
(CH2), 63.5 (C), 70.6 (CH), 72.4 (CH), 123.3 (CH), 128.6
(2ꢂCH), 129.1 (C), 129.6 (2ꢂCH), 133.5 (CH), 140.2
(CH), 155.4 (C), 165.3 (2ꢂC), 169.0 (C), 169.4 (C), 170.3
(C). Anal. Calcd for C25H31NO12: C, 55.86; H, 5.81; N,
2.61. Found: C, 55.94; H, 5.84; N, 3.02.
1
6 as a colorless oil. H NMR (400 MHz, CDCl3): d 2.01
(3H, s, CH3aCO), 2.10 (3H, s, CH3bCO), 3.68 (3H, s,
CH3aO), 3.69 (3H, s, CH3bO), 4.31–4.36 (2H, m, H4a,
H4b), 4.37–4.46 (4H, m, H2a, H2b, H6a, H6b), 4.56–4.61
(4H, m, 2ꢂH5a, 2ꢂH5b), 4.87 (1H, d, J6,6¼11.8 Hz, H6b),
5.00 (1H, d, J6,6¼11.8 Hz, H6a), 5.41 (1H, d, J2,1¼3.1 Hz,
H1b), 5.57 (1H, d, J2,1¼4.5 Hz, H1a), 5.75 (1H, s, NHa),
5.82 (1H, s, NHb), 7.43–7.49 (4H, m, Pha,b), 7.56–7.62
(2H, m, Pha,b), 7.98–8.03 (4H, m, Pha,b).
4.1.8. (2S,3S)-4-O-Acetyl-2-benzoyloxymethyl-3-O-for-
myl-2-(methoxycarbonylamino)butanal (9). To a solution
of the diol 6 (0.21 g, 0.55 mmol) in methanol (0.88 mL) was
added an aqueous solution of sodium metaperiodate (0.14 g,
0.65 mmol) in water (0.88 mL). The mixture was stirred at
room temperature for 1.5 h and then diluted with CH2Cl2.
The solid part was filtered and solvent was removed under
reduced pressure to give 0.164 g (78%) of aldehyde 9 as
a colorless oil, which was used immediately in the next
step without purification. 1H NMR (400 MHz, CDCl3):
d 2.00 (3H, s, CH3CO), 3.71 (3H, s, CH3O), 4.30 (1H, dd,
4.1.6. Ethyl (E,4S,5R,6S)-7-O-acetyl-5-benzoyloxy-
methyl-4,6-dihydroxy-5-(methoxycarbonylamino)hept-
2-enoate (7). To a solution of 6 (32 mg, 0.083 mmol) in dry
CH2Cl2 (0.80 mL) were added Ph3P]CHCO2Et (87 mg,
0.25 mmol) and benzoic acid (1 mg, 0.0083 mmol). The
reaction mixture was stirred for 22 h at room temperature.
Removal of the solvent gave a residue, which was purified
by chromatography on silica gel (hexane–ethyl acetate,
1:2) to afford 37.6 mg (85%) of compound 7 as a white solid;
mp 115–116 ꢁC; [a]D20 +32.3 (c 0.26, CHCl3); nmax (liquid
J4,4¼12.9 Hz, J4,3¼2.6 Hz, H4), 4.43 (1H, dd, J4,4
¼
12.9 Hz, J4,3¼1.9 Hz, H4), 4.89 (1H, d, J5,5¼11.6 Hz, H5),
5.05 (1H, d, J5,5¼11.6 Hz, H5), 6.02 (1H, m, H3), 6.16
(1H, br s, NH), 7.41–7.47 (2H, m, Ph), 7.56–7.61 (1H, m,
Ph), 7.91–7.94 (2H, m, Ph), 8.20 (1H, s, OCHO), 9.80
(1H, s, CHO). Anal. Calcd for C17H19NO9: C, 53.54; H,
5.02; N, 3.67. Found: C, 53.28; H, 5.23; N, 3.49.
1
film) 1720, 1713, 1703, 1693, 1233, 1093, 727 cmꢃ1. H
NMR (400 MHz, CDCl3): d 1.22 (3H, t, J¼7.2 Hz, CH3),
2.07 (3H, s, CH3CO), 3.66 (3H, s, CH3O), 4.11 (2H, q,
J¼7.2 Hz, CH2O), 4.15–4.19 (1H, m, H4), 4.25 (1H, dd,
4.1.9. (2S,3S)-4-O-Acetyl-2-benzoyloxymethyl-3-O-
formyl-2-(methoxycarbonylamino)butanoic acid (10). A
solution of NaClO2 (0.359 g, 3.97 mmol) and NaH2PO4
(0.447 g, 2.86 mmol) in water (2.30 mL) was added to the
solution of aldehyde 9 (0.164 g, 0.43 mmol) in acetoni-
trile–t-BuOH–2-methyl-2-butene (4:4:1, 9.60 mL) at 0 ꢁC
over 5 min and then stirred at the same temperature for
3 h. After evaporation of the solvent, the crude material
was poured into brine (10 mL) and extracted with ethyl
acetate (5ꢂ10 mL). The extracts were dried (Na2SO4) and
concentrated under reduced pressure. The residue was
chromatographed on silica gel (CH2Cl2–methanol, 95:5) to
afford 0.116 g (68%) of carboxylic acid 10 as a colorless
J5,5¼11.5 Hz, J5,4¼7.4 Hz, H5), 4.50 (1H, dd, J5,5
¼
11.5 Hz, J5,4¼2.0 Hz, H5), 4.56 (1H, d, J6,6¼12.0 Hz, H6),
4.63 (1H, d, J6,6¼12.0 Hz, H6), 5.00–5.05 (1H, m, H3),
5.80 (1H, br s, NH), 6.21 (1H, dd, J2,1¼15.6 Hz, J3,1
¼
1.7 Hz, H1), 7.20 (1H, dd, J2,1¼15.6 Hz, J3,2¼4.6 Hz, H2),
7.43–7.48 (2H, m, Ph), 7.56–7.61 (1H, m, Ph), 7.97–8.01
(2H, m, Ph). 13C NMR (100 MHz, CDCl3): d 14.1 (CH3),
20.9 (CH3), 52.8 (CH3), 60.5 (CH2), 63.3 (C), 63.8 (CH2),
66.0 (CH2), 71.3 (CH), 71.4 (CH), 122.8 (CH), 128.5
(2ꢂCH), 128.9 (C), 129.7 (2ꢂCH), 133.6 (CH), 145.0
(CH), 157.6 (C), 166.1 (C), 166.2 (C), 171.4 (C). Anal.
Calcd for C21H27NO10: C, 55.62; H, 6.00; N, 3.09. Found:
C, 55.70; H, 5.78; N, 3.17.
1
oil. H NMR (400 MHz, CDCl3): d 2.01 (3H, s, CH3CO),
3.61 (3H, s, CH3O), 4.21 (1H, dd, J4,4¼12.4 Hz, J4,3
¼
7.8 Hz, H4), 4.67–4.73 (1H, m, H4), 4.87 (1H, d, J5,5
¼
11.4 Hz, H5), 4.95 (1H, d, J5,5¼11.4 Hz, H5), 5.90 (1H, m,
H3), 6.29 (1H, br s, NH), 7.37–7.43 (2H, m, Ph), 7.51–
7.56 (1H, m, Ph), 7.93–7.97 (2H, m, Ph), 8.10 (1H, s,
OCHO). 13C NMR (100 MHz, CDCl3): d 20.7 (CH3), 52.6
(CH3), 62.6 (C), 62.8 (CH2), 63.5 (CH2), 70.9 (CH), 128.4
(2ꢂCH), 129.4 (C), 129.7 (2ꢂCH), 133.3 (CH), 156.2 (C),
160.2 (C), 166.0 (C), 171.4 (C), 172.1 (C). Anal. Calcd for
C17H19NO10: C, 51.39; H, 4.82; N, 3.53. Found: C, 51.60;
H, 4.68; N, 3.27.
4.1.7. Ethyl (E,4S,5R,6S)-4,6,7-tri-O-acetyl-5-benzoyl-
oxymethyl-5-(methoxycarbonylamino)hept-2-enoate (8).
To a solution of 7 (20 mg, 0.044 mmol) in pyridine
(0.018 mL) were added DMAP (1 mg, 0.008 mmol) and
acetic anhydride (10 mL, 0.106 mmol) at room temperature.
The reaction mixture was stirred overnight. Removal of sol-
vent gave a residue, which was purified by chromatography
on silica gel (hexane–ethyl acetate, 2:1) to afford 21 mg
(89%) of compound 8 as a colorless oil; [a]2D0 +42.3 (c
0.135, CHCl3). 1H NMR (400 MHz, CDCl3): d 1.23 (3H, t,
J¼7.1 Hz, CH3), 2.01 (3H, s, CH3CO), 2.06 (3H, s,
CH3CO), 2.12 (3H, s, CH3CO), 3.66 (3H, s, CH3O), 4.13
(2H, q, J¼7.1 Hz, CH2O), 4.17 (1H, dd, J5,5¼12.3 Hz,
J5,4¼6.7 Hz, H5), 4.58 (1H, dd, J5,5¼12.3 Hz, J5,4¼3.3 Hz,
H5), 4.83 (2H, m, 2ꢂH6), 5.39 (1H, br s, NH), 5.64 (1H,
dd, J5,4¼6.7, 3.3 Hz, H4), 5.88 (1H, dd, J2,1¼15.7 Hz,
J3,2¼1.5 Hz, H1), 6.14 (1H, m, H3), 6.99 (1H, dd,
J2,1¼15.7 Hz, J3,2¼5.2 Hz, H2), 7.43–7.49 (2H, m, Ph),
7.56–7.61 (1H, m, Ph), 7.98–8.01 (2H, m, Ph). 13C NMR
(100 MHz, CDCl3): d 14.1 (CH3), 20.6 (CH3), 20.8 (CH3),
4.1.10. Benzyl (2S,3S)-4-O-acetyl-2-benzoyloxymethyl-3-
O-formyl-2-(methoxycarbonylamino)butanoate (11).
K2CO3 (51 mg, 0.37 mmol) and benzyl bromide (64 mL,
0.54 mmol) were added to a solution of 10 (0.116 g,
0.29 mmol) in DMF (4.20 mL). The reaction mixture was
stirred at room temperature for 1 h, then diluted with water
(12 mL) and extracted with Et2O (2ꢂ12 mL). The combined
organic layers were dried (Na2SO4) and concentrated under
reduced pressure. The residue was purified by chromato-
graphy (hexane–ethyl acetate, 3:1) to give 0.11 g (80%) of
ester 11 as a colorless oil; [a]2D0 +52.0 (c 0.35, CHCl3);