Paper
Organic & Biomolecular Chemistry
Formylmethyl (E)-2,3-O-isopropylidene-5,6-dideoxy-1-(uracil- 61.0, 49.8, 29.8, 27.4, 25.6; ESIMS-LR m/z 494 [(M + Na)+];
1-yl)-β-D-ribo-5-ene-heptofuranuronate (14b). A solution of 19 ESIMS-HR calcd for C23H25N3NaO8 494.1539, found 494.1543.
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(94.8 mg, 0.259 mmol) in CH2Cl2–pyridine (20/1, 2 mL) was Data for 22b: H NMR (CDCl3, 400 MHz) δ 8.65 (br s, 1H, NH-
treated with Dess–Martin periodinane (145 mg, 0.337 mmol) 3), 7.35 (m, 6H Ph, H-6), 5.83 (d, 1H, H-1′, J1′,2′ = 2.3 Hz), 5.68
at room temperature for 1 h. After the reaction mixture was (dd, 1H, H-5, J5,NH = 1.7, J5,6 = 8.0 Hz), 5.03 (dd, 1H, H-3′, J3′,4′
=
diluted with EtOAc (30 mL), saturated aqueous Na2S2O3 (5 mL) 4.6, J3′,2′ = 6.1 Hz), 4.86 (dd, 1H, H-2′, J2′,1′ = 2.3, J2′,3′ = 6.3 Hz),
and saturated aqueous NaHCO3 (5 mL) were added at 0 °C, 4.37 (br t, 1H, H-3″, J3″,4′ = J3″,3″a = 6.3 Hz), 4.24 (dd, 1H, H-4′,
and the resulting biphasic layers were vigorously stirred at the J4′,3′ = 4.6, J4′,3″ = 6.3 Hz), 4.15 (dd, 1H, H-6″α, J6″α,3″a = 4.6,
same temperature for 10 min. The mixture was partitioned J6″α,6″β = 10.3 Hz), 4.10 (Bn, overlap with the peak of 21b), 3.91
between the organic phase and the aqueous phase, and the (Bn, overlap with the peak of 21b), 3.80 (br d, 1H, H-6″α,
aqueous phase was extracted with EtOAc (20 mL). The com- J6″α,6″β = 10.3 Hz), 3.45 (dd, 1H, H-6″β, J6″β,6″a = 5.2, J6″β,6″α
=
bined organic phase was washed with brine (20 mL), dried 8.0 Hz) 3.65 (1H, H-6″a, overlap with the peak of 21b), 3.55
with Na2SO4, filtered and concentrated in vacuo to afford 14b (dd, 1H, H-3″a, J3″a,3″ = 5.2, J3″a,6″a = 8.1 Hz), 1.56 (s, 3H, aceto-
(75.5 mg, 80%) as a colorless foam, which was used for the nide), 1.35 (s, 3H, acetonide); 13C NMR (CDCl3, 100 MHz)
next reaction without further purification. [α]2D1 +20.5° (c 1.00, δ 175.9, 163.5 (overlap with a peak of 21b), 150.2, 141.7, 134.9,
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CH3CN); H NMR (CDCl3, 500 MHz) δ 9.64 (s, 1H, CHO), 8.29 128.6, 128.5, 128.4, 115.3, 102.8, 93.1, 87.1, 83.9, 80.1, 69.1
(br s, 1H, NH-3), 7.20 (d, 1H, H-6, J6,5 = 8.0 Hz), 7.05 (dd, 1H, (overlap with a peak of 21b), 67.7, 61.2, 51.0, 29.8(overlap with
H-5′, J5′,4′ = 5.7, J5′,6′ = 16.0 Hz), 6.04 (dd, 1H, H-6′, J6′,4′ = 1.8, a peak of 21b), 27.3, 25.5. Data for the major diastereomer of
J6′,5′ = 16.0 Hz), 5.76 (dd, 1H, H-5, J5,NH = 1.7, J5,6 = 8.0 Hz), 23; 1H NMR (CDCl3, 400 MHz) δ 8.25 (br s, 1H, NH-3), 7.38 (m,
5.60 (d, 1H, H-1′, J1′,2′ = 1.2 Hz), 5.12 (dd, 1H, H-2′, J2′,1′ = 1.2, 5H, Ph), 7.18 (d, 1H, H-6, J6,5 = 8.0 Hz), 5.68 (dd, 1H, H-5, J5,NH
J2′,3′ = 4.0 Hz), 4.90 (dd, 1H, H-3′, J3′,2 = 4.0, J3′,4′ = 6.3 Hz), 4.73 = 2.3, J5,6 = 8.0 Hz), 5.51 (d, 1H, H-1′, J1′,2′ = 1.7 Hz), 4.97 (dd,
(s, 2H, CH2CHO), 4.70 (ddd, H-4′, J4′,6′ = 1.8, J4′,5′ = 5.7, J4′,3′
=
1H, H-2′, J2′,1′ = 1.7, J2′,3′ = 6.3 Hz), 4.70 (dd, 1H, H-3′, J3′,4′ = 4.6,
6.3 Hz), 1.65 (s, 3H, acetonide), 1.36 (s, 3H, acetonide); 13C J3′,2′ = 6.3 Hz), 4.27 (d, 1H, Bn, J = 13.7 Hz), 4.21 (d, 1H, Bn, J =
NMR (CDCl3, 125 MHz) δ 214.3, 162.8, 150.0, 144.6, 143.0, 13.7 Hz), 4.04 (dd, H-4′, J4′,3′ = 4.6, J4′,5′ = 6.3 Hz), 3.87 (m, 1H,
121.9, 114.8, 103.1, 95.8, 89.3, 87.1, 84.4, 84.2, 66.4, 61.2, 27.2, H-5′), 2.68 (dd, H-6′α, J6′α,5′ = 4.6, J6′α,6′β = 18.3 Hz), 2.65 (dd,
25.3; APCIMS-LR m/z 391 [(M + Na)+]; APCIMS-HR calcd for H-6′β, J6′β,5′ = 4.6, J6′β,6′α = 18.3 Hz), 1.54 (s, 3H, acetonide), 1.32
C16H20N2NaO8 391.1117, found 391.1110.
(s, 3H, acetonide); 13C NMR (CDCl3, 100 MHz) δ 175.9, 163.3,
4-[(3R, 3aR, 6aR)-1-Aza-1-N-benzyl-2,5-oxa-4-oxobicyclo[3.3.0]- 150.0, 143.5, 134.3, 129.9, 129.3, 128.2, 115.0, 102.9, 95.9, 86.8,
octan-3-yl]-2,3-O-isopropylidene-1-(uracil-1-yl)-β-D-erythro-fura- 84.5, 81.5, 63.1, 30.8, 27.2, 25.2. Data for the minor diastereo-
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nose (21b) and 4-[(3S, 3aS, 6aS)-1-Aza-1-N-benzyl-2,5-oxa-4-oxo- mer of 23; H NMR (CDCl3, 400 MHz) δ 8.03 (br s, 1H, NH-3),
bicyclo[3.3.0]octan-3-yl]-2,3-O-isopropylidene-1-(uracil-1-yl)-β-D- 7.34 (m, 6H, Ph, H-6), 5.76 (dd, 1H, H-5, J5,NH = 2.3, J5,6
=
erythro-furanose (22b). A solution of 14b, BnNHOH (123 mg, 8.0 Hz), 5.68 (d, 1H, H-1′, J1′,2′ = 2.3 Hz), 4.85 (dd, 1H, H-2′,
1.00 mmol) and MS4A (10 g) in MeCN (100 mL) was stirred at J2′,1′ = 2.3, J2′,3′ = 6.3 Hz), 4.54 (dd, 1H, H-3′, J3′,4′ = 4.0, J3′,2′
room temperature for 7 days. The reaction mixture was filtered 6.3 Hz), 4.22 (s, 2H, Bn), 4.13 (dd, H-4′, J4′,3′ = 4.0, J4′,5′
off through a Celite pad, and the filtrate was concentrated 6.3 Hz), 3.75 (m, 1H, H-5′), 2.84 (dd, H-6′α, J6′α,5′ = 8.6, J6′α,6′β
=
=
=
in vacuo. The residue was purified by flash silica gel column 17.8 Hz), 2.61 (dd, H-6′β, J6′β,5′ = 8.6, J6′β,6′α = 17.8 Hz), 1.54 (s,
chromatography (2 × 60 cm, EtOAc–hexane, 33%) to afford a 3H, acetonide), 1.32 (s, 3H, acetonide); 13C NMR (CDCl3,
mixture of 21b, 22b, and 23 as a colorless foam (Table 1, entry 100 MHz) δ 174.8, 163.5 (overlap with a peak of 21b), 150.4,
1, 21b : 22b : 23 = 60 : 13 : 27). A part of the mixture was separ- 142.8, 134.3, 129.8, 129.3 (overlap with a peak of 21b), 128.3,
ated by flash silica gel column chromatography (2 × 60 cm, 115.3(overlap with a peak of a major product containing an
EtOAc–hexane, 20%) to obtain 21b as a colorless foam and isoxazolidine ring), 103.2, 94.9, 88.7, 84.4, 81.7, 63.5, 31.0, 27.4
a mixture of isoxazolidinone compound 23. Data for 21b: (overlap with a peak of 21b), 25.4.
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[α]2D1 +61.8° (c 12.2, CHCl3); H NMR (CDCl3, 400 MHz) δ 8.85
4-[(3R, 3aR, 6aR)-1-Aza-1-N-(3-tert-butoxycarbonylamino-
propyl)-2,5-oxa-4-oxobicyclo[3.3.0]octan-3-yl]-2,3-O-isopropylidene-
1-(uracil-1-yl)-β-D-erythro-furanose (26) and 4-[(3S, 3aS, 6aS)-
(br s, 1H, NH-3), 7.35 (m, 5H, Ph), 7.23 (d, 1H, H-6, J6,5
8.0 Hz), 5.61 (d, 1H, H-1′, J1′,2′ = 2.3 Hz), 5.56 (d, 1H, H-5, J5,6
=
=
8.0 Hz), 4.98 (dd, 1H, H-2′, J2′,1′ = 2.3, J2′,3′ = 6.3 Hz), 4.94 (dd, 1-Aza-1-N-(3-tert-butoxycarbonylaminopropyl)-2,5-oxa-4-oxobicyclo-
1H, H-3′, J3′,4′ = 4.6, J3′,2′ = 6.3 Hz), 4.50 (dd, 1H, H-3″, J3″,4′
4.6, J3″,3″a = 5.2 Hz), 4.29 (dd, 1H, H-4′, J4′,3″ = 3.4, J4′,3′
=
=
[3.3.0]octan-3-yl]-2,3-O-isopropylidene-1-(uracil-1-yl)-β-D-erythro-
furanose (27). A suspension of 14b (75.5 mg) and MS4A (2.1 g)
4.6 Hz), 4.24 (dd, 1H, H-6″α, J6″α,3″a = 4.6, J6″α,6″β = 10.8 Hz), in CH2Cl2 (21 mL) was treated with the hydroxylamine 25
4.10 (d, 1H, Bn, J = 13.2 Hz), 3.98 (d, 1H, Bn, J = 13.8 Hz), 3.95 (38.0 mg, 0.200 mmol) at room temperature for 7 days. The
(br d, 1H, H-6″α, J6″α,6″β = 10.8 Hz), 3.45 (dd, 1H, H-6″β, J6″β,6″a MS4A was filtered off through a Celite pad, and the filtrate was
= 4.6, J6″β,6″α = 10.8 Hz), 3.72 (dd, 1H, H-3″a, J3″a,3″ = 5.2, J3″a,6″a concentrated in vacuo. The residue was purified by preparative
= 8.1 Hz), 3.65 (br dd, 1H, H-6″a, J6″a,6″β = 4.6, J6″a,3″a = 8.1 Hz), HPLC (YMC-Pack R&D SIL 250 × 20 mm i.d., S-5 μm 12 nm,
1.56 (s, 3H, acetonide), 1.35 (s, 3H, acetonide); 13C NMR MeOH–CHCl3, 10%) to afford a mixture of diastereoisomers
(CDCl3, 100 MHz) δ 176.4, 163.5, 150.3, 142.7, 135.5, 129.0, (34.8 mg, 25% over 3 steps) as colorless foam. The mixture of
128.9, 128.8, 115.3, 102.7, 94.7, 84.6, 83.7, 79.7, 69.1, 67.9, diastereo isomers was further purified by preparative HPLC
Org. Biomol. Chem.
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