(3S,4R,5R)-5-(tert-Butoxycarbonylaminomethyl)-3,4-di-
hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one (14).
of acetonitrile and water (86 : 16 v/v, 6 ml) and brought
to reflux. A suspension of Wilkinson’s catalyst (74 mg,
0.08 mmol) in acetonitrile–water (86 : 16 v/v, 5 ml) was added.
The reaction was then allowed to reflux vigorously for 3 h. Then
the mixture was cooled to room temperature. The reaction was
treated with NaHCO3 (200 mg, 2.38 mmol), and then a solution
of (Boc)2O (124 mg, 0.57 mmol) in CH2Cl2 (6 ml) was added.
The reaction was complete after 3 h. The solvent was removed,
the residue was dissolved in water (15 ml), extracted with
chloroform (3 × 20ml) and the combined organic phases were
dried with MgSO4. The solvent was removed and the residue
chromatographed (chloroform–ethyl acetate 6 : 1) to give com-
pound 17 (21 mg, 64%) as a colourless oil. [α]2D0 = Ϫ11.9 (c 1.0,
A solution of 1213 (74 mg, 0.21 mmol) in dry EtOH (100 ml)
was hydrogenated over Pd/C (10%) under normal pressure at
room temperature for about 16 h. The catalyst was removed by
filtration and the solvent evaporated to obtain 13 (55 mg). Now
TEMPO (4 mg, 0.026 mmol) and Bu4NϩBrϪ (4 mg, 0.012
mmol) in CH2Cl2 (9 ml) were added. Then MCPBA (58–85%,
80 mg, 0.27–0.39 mmol) was added in portions until the starting
material disappeared. The reaction mixture was concentrated
in vacuo. The residue was purified by chromatography (CHCl3–
MeOH 20 : 1) to give the desired product, which was contamin-
ated by some MCPBA. This product was further purified
by chromatography (pentane–ethyl acetate 2 : 1) to furnish 14
(16 mg, 30%) as an oil. 1H NMR (200 MHz, CDCl3): δ 5.12 (t,
1H, J 6.0 Hz, NH), 4.32 (t, 1H, J5,6ax = J6ax,6eq 11.0 Hz, H-6ax),
4.31 (d, 1H, J3,4 5.8 Hz, H-3), 4.20 (dd, 1H, J5,6eq 4.6 Hz,
H-6eq), 4.03 (t, 1H, J4,5 5.8 Hz, H-4), 3.60–3.35 (m, 2H, OH,
H-5Јa), 3.10 (dt, 1H, JNH,5Јb = J5,5bЈ 4.6, J5Јa,5Јb 14.4 Hz, H-5Јb),
2.32 (m, 1H, H-5), 1.43 [s, 9H, (CH3)3C]. 13C NMR (50 MHz,
1
CHCl3). H NMR (200 MHz, CDCl3): δ 5.02 (br s, 1H, NH),
4.12 (dt, 1H, J3,4 = J4,5a 5.3 Hz, J4,5b 7.2 Hz, H-4), 4.10 (dd, 1H,
J2,3 7.2 Hz, H-3), 3.64 (dd, 1H, J2,2Јa 5.0 Hz, J2Јa,2Јb 10.5 Hz,
H-2Јa), 3.62 (dd, 1H, J5a,5b 10.5 Hz, H-5), 3.50 (dd, 2H, J2,2Јb 7.2
Hz, H-5b, H-2Јb), 3.28 (dd, 1H, J1a,2 5.5 Hz, J1a,1b 13.8 Hz,
H-1a), 3.16 (dd, 1H, J1a,2 6.2 Hz, H-1b), 2.33 (1H, OH),
2.06–1.91 (m, 1H, H-2), 1.35 (s, 9H, t-BuO), 1.35/1.28 (s, 6H,
2 × CH3), 0.80 (s, 9H, t-BuSi), 0.04 [s, 6H, Si(CH3)2]. 13C NMR
(50 MHz, CDCl3): δ 156.2 (–NCOO–), 107.6 (O–C–O), 79.2
(–COOC(CH3)3), 78.1* (C-3), 77.9* (C-4), 64.1 (C-2Ј), 61.9
(C-5), 41.1** (C-1), 40.2** (C-2), 28.6 (–COOC(CH3)3),
28.5*** (MeC), 26.1 [–Si(CH3)2C(CH3)3], 25.8*** (MeC), 18.2
[Si(CH3)2C(CH3)3]. HRMS (ES): m/z 442.2600 (M ϩ Naϩ),
calcd for C20H41O6NSi ϩ Naϩ 442.2600.
CDCl ): δ 173.6 (C-2), 155.6 (C᎐O), 80.7 [(CH ) C], 72.9 (C-3),
᎐
3
3 3
70.2 (C-4), 66.8 (C-6), 40.8 (C-5Ј), 37.2 (C-5), 28.5 [(CH3)3C].
HRMS (ES): calcd for C11H19NO6 ϩ Naϩ 284.1110, found
284.1110.
(3S,4R,5R)-3,4-Dihydroxy-5-hydroxymethylpiperidin-2-one (9)
Pyranone 14 (16 mg, 0.061 mmol) was treated with aqueous
HCl (1.2 M, 1 ml) for 5 min to give 9 (10 mg, quant.) as a
colourless oil. 1H NMR (200 MHz, D2O): δ 3.99 (d, 1H, J3,4 9.3
Hz, H-3), 3.91–3.60 (m, 3H, H-4, H-5Јa, H-5Јb), 3.35 (dd, 1H,
J5,6eq 5.4, J6eq,6ax 12.0 Hz, H-6eq), 3.12 (t, 1H, J5,6ax 12.0 Hz,
H-6ax), 2.13 (m, 1 H, H-5). 13C NMR (50 MHz, D2O): δ 173.1
(C-2), 70.8 (C-3), 69.8 (C-4), 59.7 (C-5Ј), 40.8 (C-6), 38.7 (C-5).
HRMS (ES): calcd for C6H11NO4 ϩ Naϩ 184.0586, found
184.0586.
(3S,4S,5R)-1-(tert-Butoxycarbonyl)-5-(tert-butyldimethyl-
siloxymethyl)-3,4-dihydroxy-3,4-O-isopropylidenepiperidin-2-
one (18)
To a mixture of 17 (38 mg, 0.09 mmol), Bu4NBr (10 mg, 0.03
mmol) and 0.66 eq. of TEMPO (10 mg, 0.06 mmol) in CH2Cl2
(5 ml) was slowly added MCPBA (57–72%, 55 mg, 0.18–0.23
mmol) until the starting material disappeared. The mixture was
washed with saturated NaHCO3 (3 × 10 ml) and the organic
phase was dried with MgSO4, filtered and concentrated. The
residue was chromatographed (ethyl acetate–pentane 1 : 5) to
give the product 18 as a colourless oil (32 mg, 86%). 1H
NMR(200 MHz, CDCl3): δ 4.46 (s, 2H, H-3, H-4), 3.89 (dd,
1H, J5,6eq 3.6 Hz, J6ax,6eq 12.8 Hz, H-6eq), 3.67 (dd, 1H, J5,5Јa 6.3
Hz, J5Јa,5Јb 9.9 Hz, H-7a), 3.51 (dd, 1H, J5,5Јb 7.8 Hz, H-7b), 3.31
(dd, 1H, J5,6ax 11.2 Hz, H-6ax), 2.14–2.00 (m, 1H, H-5), 1.46 (s,
9H, t-BuO), 1.40/1.28 (s, 6H, 2 × CH3), 0.83 (s, 9H, t-BuSi),
0.04 [s, 6H, Si(CH3)2]. 13C NMR (50 MHz, CDCl3): δ 168.7
(C-2), 151.9 [COOC(CH3)3], 110.7 (O–C–O), 83.7 [COOC-
(CH3)3], 76.6* (C-3), 73.4* (C-4), 61.2 (C-5Ј), 41.9 (C-6), 40.2
(C-5), 28.1 [COOC(CH3)3], 26.4** (CCH3), 26.0** (CCH3),
26.1 [Si(CH3)2C(CH3)3], 18.4 [Si(CH3)2C(CH3)3]. HRMS (ES):
m/z 438.2297 (M ϩ Naϩ) calcd for C20H37O6NSi ϩ Naϩ
438.2288.
1-Allylamino-2-(tert-butyldimethylsiloxymethyl)-1,2-dideoxy-
3,4-O-isopropylidene-D-ribitol (16).
Compound 15 (46 mg, 0.14 mmol) was dissolved in methanol
(6 ml). A solution of allylamine (17 mg, 0.29 mmol) was neu-
tralised to pH 6 using glacial acetic acid, and this solution was
added to the solution of aldehyde 15. The reaction was then
treated with NaCNBH3 (2 mg, 0.03 mmol). The transformation
was complete within 2 h at room temperature. The solvent was
removed, and the reaction was dissolved in chloroform (20 ml),
the mixture was washed with aq. 10% Na2CO3(15 ml). The
aqueous phase was extracted with chloroform (2 × 15 ml), the
combined organic phases were dried over MgSO4, and the sol-
vent was removed. The residue was purified by column chrom-
atography (methanol–chloroform 1 : 20) to furnish 16 (28 mg,
57%) as a clear oil. [α]2D0 = Ϫ18.3, (c 0.8, CHCl3). 1H NMR (200
MHz, CDCl3): δ 5.83 (ddt, 1H, J6a,7 = J6b,7 6.0 Hz, J7,8a(cis) 10.2
Hz, J7,8b(trans) 17.2 Hz, H-7), 5.12 (dq, 1H, J6a,8b = J6b,8b = J8a,8b
1.8 Hz, H-8b), 5.04 (dq, 1H, J6a,8a = J6b,8a 1.8 Hz, H-8a), 4.12 (q,
1H, J3,4 = J4,5a = J4,5b 5.8 Hz, H-4), 4.04 (dd, 1H, J2,3 8.2 Hz, H-
3), 3.65–3.40 (m, 4H, H-5a, H-5b, H-2Јa, H-2Јb), 3.18 (dt, 2H,
H-6a, H-6b), 2.80 (dd, 1H, J1a,1b 12.0 Hz, J1a,2 5,2 Hz, H-1a),
2.51 (dd, 1H, J1b,2 5.2 Hz, H-1b), 2.64–2.46 (1H, OH), 2.08–1.92
(m, 1H, H-2), 1.38/1.25 [s, 6H, C(CH3)2], 0.90 (s, 9H, t-Bu), 0.04
[s, 6H, Si(CH3)2]. 13C NMR (50 Hz, CDCl3): δ 136.7 (C-7),
116.1 (C-8), 107.5 [C(CH3)2], 78.4*(C-3), 78.0* (C-4), 64.4 (C-
2Ј), 61.5 (C-5), 52.7 (C-6), 48.9 (C-1), 40.2 (C-2), 28.4**
(CH3C), 26.0 (C(CH3)3), 25.8** (CH3C), 18.2 (C(CH3)3, MeSi
signals are below zero. HRMS (ES): m/z 360.2566 (M ϩ Hϩ)
calcd for C18H37O4NSi ϩ Hϩ 360.2570.
(3S,4S,5R)-3,4-Dihydroxy-5-hydroxymethylpiperidin-2-one (10)
A solution of 18 (18 mg, 0.04 mmol) in CF3COOH–H2O 5 : 1
was stirred for 5 min at room temperature. Concentration of the
mixture gave 1012 (6 mg) in essentially quantitative yield.
(3R,4R,5R)-1-(tert-Butyloxycarbonyl)-3,4-O-isopropylidene-
3,4-dihydroxy-5-methylpiperidin-2-one (20)
To a solution of 19 (20 mg, 0.070 mmol), TEMPO (5 mg, 0.032
mmol) and Bu4NϩBrϪ (4 mg) in CH2Cl2 was added MCPBA
(58–85%, 40 mg, 0.13–0.20 mmol) at room temperature. The
solution obtained was stirred for 18 h at the same temperature.
After the reaction, the solution was washed with a saturated
aqueous solution of NaHCO3 and concentrated in vacuo. The
residue was purified by chromatography (pentane–ethyl acetate
3 : 1) to give 20 (12 mg, 60%) as a colourless oil. 1H NMR (200
MHz, CDCl3): δ 4.45 (d, 1H, J3,4 6.8 Hz, H-3), 4.34 (ddd, 1H,
1-(tert-Butoxycarbonylamino)-2-(tert-butyldimethylsiloxy-
methyl)-1,2-dideoxy-3,4-O-isopropylidene-D-ribitol (17)
Compound 16 (28 mg, 0.08 mmol) was dissolved in a mixture
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 8 2 – 2 8 7
286