δC 26.1, 26.5, 29.6, 52.2, 58.4, 64.2, 72.6, 72.8, 76.7, 80.1, 81.4,
109.8, 120.2, 120.3, 125.4, 125.9, 126.2, 127.5, 127.6, 128.4,
128.7, 128.8, 129.2, 140.6, 141.0, 142.0, 147.1, 147.3 and 174.6
(Found: C, 70.5; H, 6.6; N, 2.6. C29H31NO6 requires C, 71.1; H,
6.4; N, 2.9%).
MeOH (100 cm3). The remaining residue was eluted with 3 mol
dm3 NH4OH. The ammoniacal solution was evaporated, then
co-evaporated with toluene to give free base 1 (52 mg, 76%) as a
sticky oil, [α]D20 ϩ8.1 (c 0.98, water) {lit.,2a mp 115 ЊC; [α]D20 ϩ7.8
(c 0.46, water)}; δH(D2O) 2.78 (1 H, dd, J 12.2 and 5.7), 2.94
(1 H, m), 3.06 (1 H, dd, J 12.2 and 5.7), 3.58 (1 H, dd, J 11.5 and
4.9), 3.76 (1 H, m) and 4.06 (1 H, m); δC 48.9, 59.8, 64.1, 75.1
and 76.7.
Methyl 2-deoxy-3,4-O-isopropylidene-2-[(9-phenylfluoren-9-yl)-
amino]-D-lyxonate 8
To a solution of diol 7 (4.3 g, 8.6 mmol) in EtOH (20 cm3) was
added aq. NaIO4 (2.1 g, 10.3 mmol) in (6.5 cm3), then the mix-
ture was stirred for 2 h. After the alcohol spot for substrate 7
had disappeared on TLC, to the reaction mixture was added
NaBH4 (0.39 g, 10.3 mmol) and the mixture was stirred for
another 10 min before being evaporated, then water (20 cm3) was
added and the mixture was extracted with EtOAc (30 cm3 × 3).
The organic phase was washed with brine, dried, and concen-
trated under reduced pressure. The residue was chromato-
graphed on silica gel [hexane–EtOAc (3:1)] to give compound 8
(3.9 g, 98%) as a solid, mp 64–66 ЊC; [α]D20 Ϫ150 (c 1.16, CHCl3);
δH 1.09 (3 H, s), 1.28 (3 H, s), 2.63 (1 H, d), 3.23 (3 H, s), 3.35
(1 H, s, OH), 3.76–3.92 (4 H, m) and 7.09–7.73 (13 H, m); δC
26.4, 26.8, 51.9, 58.6, 63.8, 72.6, 80.2, 80.3, 109.5, 120.2, 125.5,
125.7, 126.1, 127.4, 127.5, 128.4, 128.5, 128.6, 128.9, 140.4,
141.1, 143.1, 147.9 and 174.7 (Found: C, 72.8; H, 6.5; N. 3.4.
C28H29NO5 requires C, 73.2; H, 6.4; N, 3.1%).
To the free base was added conc. HCl. The mixture was
evaporated, then co-evaporated with toluene. The crystalline
residue was recrystallised from methanol–diethyl ether to afford
1
compound 1 as its hydrochloride salt. H and 13C NMR data
were consistent with those reported, mp 113–114 ЊC; [α]D20 ϩ34.7
(c 0.78, water) {lit.,3a mp 115 ЊC; [α]D20 ϩ37.9 (c 0.53, water)}
(Found: C, 35.0; H, 7.4; N, 8.1. Calc. for C5H12ClNO3: C, 35.4;
H, 7.1; N, 8.3%).
2,3:4,5-Di-O-isopropylidene-D-arabinitol 11
To an ice-cooled solution of LiAlH4 (758 mg, 20.0 mmol) in
THF (3 cm3) was added a solution of gluconate 10 (5.8 g, 20.0
mmol) in THF (25 cm3). The reaction mixture was warmed to
rt, stirred for 2 h, and quenched by the sequential addition of
water (0.76 cm3), 15% aq. NaOH (0.76 cm3), and water (2.5
cm3). The mixture was filtered, and the filtrate was concentrated
under reduced pressure to give the corresponding alcohol which
was used in the next step without further purification. To a
solution of the corresponding alcohol in EtOH (25 cm3) were
added NaIO4 (5.1 g, 24 mmol) and water (10 cm3), and the
mixture was stirred for 2 h. To the reaction mixture was added
NaBH4 (453 mg, 12 mmol) and the mixture was stirred for 10
min before being evaporated. The residue was then treated with
water (25 cm3) and extracted with EtOAc (50 cm3 × 3). The
combined organic phase was washed with brine, dried, and
concentrated under reduced pressure. The residue was chrom-
atographed on silica gel [hexane–EtOAc (4:1)] to give
compound 11 (4.31 g, 93%) as an oil, [α]D20 Ϫ2.1 (c 1.0, CHCl3);
δH 1.28 (3 H, s), 1.32 (3 H, s), 1.33 (3 H, s), 1.35 (3 H, s), 2.58
(1 H, m, OH), 3.63–3.67 (2 H, m), 3.74 (1 H, m), 3.90 (1 H, dd),
3.95 (1 H, m), 4.00 (1 H, m) and 4.09 (1 H, dd); δC 24.9, 26.4,
26.6, 26.7, 62.6, 67.6, 76.6, 78.3, 80.6, 109.2 and 109.6 (Found:
C, 57.2; H, 8.9. C11H20O5 requires C, 56.9; H, 8.7%).
Methyl 2-deoxy-3,4-O-isopropylidene-5-O-methylsulfonyl-2-[(9-
phenylfluoren-9-yl)amino]-D-lyxonate 9
To a solution of alcohol 8 (2.8 g, 6.1 mmol) in THF (15 cm3)
were added triethylamine (630 mg, 6.24 mmol) and methane-
sulfonyl chloride (714 mg, 6.24 mmol). The reaction mixture
was stirred for 20 min at rt, then was quenched with saturated
aq. NaHCO3 (20 cm3). The organic phase was separated, and
the aqueous phase was extracted with CH2Cl2 (20 cm3 × 2). The
combined organic phase was washed successively water and
brine, dried, and concentrated under reduced pressure. The
residue was chromatographed on silica gel [hexane–EtOAc
(5:1)] to give compound 9 (3.2 g, 97%) as a solid, mp 155–
158 ЊC; [α]D20 Ϫ204 (c 1.00, CHCl3); δH 1.10 (3 H, s), 1.31 (3 H, s),
2.62 (1 H, dd), 3.12 (3 H, s), 3.24 (3 H, s), 3.82 (1 H, dd), 4.00
(1 H, m), 4.46 (1 H, dd), 4.77 (1 H, dd) and 7.11–7.74 (13 H, m);
δC 26.6, 26.8, 37.8, 51.9, 58.8, 70.3, 72.6, 78.0, 78.2, 110.6, 120.2,
120.3, 125.1, 125.9, 126.1, 127.5, 128.3, 128.5, 128.6, 128.8,
140.1, 141.3, 143.4, 147.9, 148.2 and 174.4 (Found: C, 64.4; H,
6.0; N, 2.4. C29H31NO7S requires C, 64.8; H, 5.8; N, 2.6%).
2,3:4,5-Di-O-isopropylidene-1-O-methylsulfonyl-D-arabinitol 12
To a solution of alcohol 11 (1.1 g, 4.8 mmol) in THF (7 cm3)
were added triethylamine (583 mg, 5.8 mmol) and methanesul-
fonyl chloride (659 mg, 5.8 mmol) at 0 ЊC. After stirring of the
mixture for 1 h at 0 ЊC, 5% aq. citric acid (20 cm3) was added
and the mixture was extracted with EtOAc (30 cm3 × 3). The
combined extracts were washed with brine, dried, and evapor-
ated, and the residue was chromatographed on silica gel
[hexane–EtOAc (4:1)] to give compound 12 (1.45 g, 97%) as a
solid, mp 110–112 ЊC; [α]D20 ϩ2.6 (c 1.3, MeOH); δH 1.27–1.35 (12
H, m), 3.00 (3 H, s), 3.66 (1 H, m), 3.89 (1 H, dd), 3.95 (1 H, m),
4.07–4.11 (2 H, m), 4.24 (1 H, m) and 4.46 (1 H, dd); δC 27.4,
29.0, 29.2, 29.3, 40.0, 70.1, 71.5, 79.1, 79.6, 80.6, 112.3 and 112.7
(Found: C, 46.2; H, 7.4. C12H22O7S requires C, 46.4; H, 7.1%).
4-Deoxy-2,3-O-isopropylidene-1-O-methylsulfonyl-4-[(9-
phenylfluoren-9-yl)amino]-D-arabinitol 4
To an ice-cooled solution of LiAlH4 (60 mg, 1.6 mmol) in THF
(2 cm3) was added a solution of mesyl ester 9 (850 mg, 1.6
mmol) in THF (5 cm3). The reaction mixture was warmed to rt,
stirred for 30 min, then quenched by sequential addition of
water (60 mm3), 15% aq. NaOH (60 mm3), and water (180
mm3). The mixture was filtered, and the filtrate was concen-
trated under reduced pressure. The residue was chromato-
graphed on silica gel [CH2Cl2–EtOAc (50:1)] to give compound
4 (709 mg, 87%) as an oil, [α]D20 Ϫ48 (c 1.10, CHCl3); δH 1.21
(3 H, s), 1.32 (3 H, s), 1.96 (1 H, s, OH), 2.22 (1 H, dd), 2.79
(1 H, dd), 3.03 (3 H, s), 3.34 (1 H, d), 3.73 (1 H, dd), 4.00 (1 H,
m), 4.21 (1 H, dd), 4.38 (1 H, dd) and 7.19–7.72 (13 H, m); δC
26.7, 26.8, 26.9, 37.6, 51.8, 55.1, 60.5, 67.7, 70.2, 72.3, 78.0,
109.6, 115.3, 120.2, 124.6, 125.5, 125.9, 127.5, 128.1, 128.2,
128.4, 128.6, 140.3, 144.4, 149.0 and 150.6 (Found: C, 65.7, H,
6.3; N, 2.6. C28H31NO6S requires C, 66.0; H, 6.1; N, 2.8%).
1-[(Benzyloxycarbonyl)amino]-1-deoxy-2,3:4,5-di-O-
isopropylidene-D-arabinitol 14
To a solution of mesylate 12 (520 mg, 1.7 mmol) in dried DMF
(3 cm3) was added NaN3 (78 mg, 5.1 mmol). After stirring of
the mixture overnight at 60 ЊC, water (10 cm3) was added and the
mixture was extracted with EtOAc (20 cm3 × 3). The combined
extracts were washed with brine, dried, and evaporated. A solu-
tion of the crude residue in EtOAc (5 cm3) was hydrogenated
over 10% palladium on charcoal (50 mg) at atmospheric
pressure for 6 h. The mixture was filtered, and the filtrate was
concentrated under reduced pressure. To a solution of the oily
residue amine 13 in CH2Cl2 (10 cm3) was added aq. K2CO3
(470 mg, 3.4 mmol in 7 cm3) and the mixture was cooled in an
1,4-Dideoxy-1,4-imino-D-arabinitol 1 and its hydrochloride salt
A solution of multi-protected compound 4 (260 mg, 0.51 mmol)
and iodine (60 mg) in methanol (1.5 cm3) was refluxed over-
night, cooled to rt, and then treated with Dowex 50W-8X (200
mg). The mixture was filtered, and the residue was washed with
J. Chem. Soc., Perkin Trans. 1, 1998
2879