Davis et al.
(ES + ve) calcd for C32H37NO6Na (M + Na+) 554.2519, found
554.2524. 1H NMR (300 MHz, CDCl3) δ 7.44-7.20 (m, 15H,
Ar), 5.87 (dd, 1H, J ) 6.4, 1.8 Hz, H4), 5.81 (d, 1H, J ) 6.6
Hz, H3), 4.70-4.62 (m, 1H, H2), 4.22 (dd, 1H, J ) 15.9, 1.5
Hz, H5), 3.98 (dd, 1H, J ) 15.6, 3.0 Hz, H5), 3.86-3.83 (m,
1H, H3′), 3.81-3.78 (m, 1H, H2′), 3.53 (br s, 1H, H1′), 3.33
(dd, 1H, J ) 9.6, 4.8 Hz, H4′), 3.15 (dd, 1H, J ) 9.6, 4.8 Hz,
H4′), 1.47 (s, 9H, tBu); 13C NMR δ 157.0 (CO), 143.8 (C), 128.6
(CH), 128.5 (CH), 127.8 (CH), 127.0 (CH), 126.4 (CH), 86.6 (C),
80.8 (C), 75.3 (CH), 72.5 (CH), 69.5 (CH), 67.2 (CH), 64.3 (CH2),
54.3 (CH2), 28.4 (CH3).
pound 11 (270 mg, 54%) as a white solid and the amino alcohol
10 (190 mg, 37%) as a brown oil. 10: [R]22D -21 (c 1.34, CHCl3);
MS (CI + ve) m/z 674 (M + H+, 2%); HRMS (ES + ve) calcd
1
for C43H48NO6 (M + H+) 674.3481, found 674.3504. H NMR
(300 MHz, CDCl3) δ 7.33-7.21 (m, 25H, Ar), 4.82 (d, 1H, J )
11.4 Hz, CH2Ph), 4.72 (d, 1H, J ) 11.4 Hz, CH2Ph), 4.68 (d,
1H, J ) 11.1 Hz, CH2Ph), 4.64 (d, 1H, J ) 11.7 Hz, CH2Ph),
4.60 (d, 1H, J ) 11.1 Hz, CH2Ph), 4.57 (d, 1H, J ) 11.4 Hz,
CH2Ph), 4.54 (d, 1H, J ) 12.0 Hz, CH2Ph), 4.46 (d, 1H, J )
12.0, CH2Ph), 4.41 (d, 1H, J ) 11.4 Hz, CH2Ph), 4.02 (dd, 1H,
J ) 5.7, 5.1 Hz, H3), 3.90-3.85 (m, 1H, H4), 3.83-3.79 (m,
1H, H1′), 3.78-3.73 (m, 1H, H3′), 3.72-3.69 (m, 1H, H4′),
3.69-3.66 (m, 1H, H2′), 3.65-3.61 (m, 1H, H4′), 3.39 (dd, 1H,
J ) 5.4, 4.8 Hz, H2), 2.98 (dd, 1H, J ) 12.0, 4.5 Hz, H5), 2.90
(dd, 1H, J ) 12.0, 4.5 Hz, H5); 13C NMR δ 138.6 (C), 138.2
(C), 138.11 (C), 138.06 (C), 138.0 (C), 128.3 (CH), 128.25 (CH),
128.23 (CH), 128.0 (CH), 127.9 (CH), 127.8 (CH), 127.7 (CH),
127.64 (CH), 127.60 (CH), 127.4 (CH), 80.6 (CH), 80.2 (CH),
79.7 (CH), 78.6 (CH), 77.6 (CH), 74.8 (CH2), 74.3 (CH2), 72.1
(CH2), 71.9 (CH2), 71.4 (CH2), 62.1 (CH), 61.2 (CH2), 48.9 (CH2).
ter t-Bu t yl (2R,3S,4R)-3,4-Dih yd r oxy-2-[(2S,3S)-1,2,3-
t r ih yd r oxy-4-t r ip h en ylm et h yloxyb u t yl]p yr r olid in e-1-
ca r boxyla te (8). To a solution of the olefin 7 (1.56 g, 2.932
mmol) in acetone (15 mL) and water (15 mL) was added
potassium osmate dihydrate (54 mg, 0.147 mmol) and N-
morpholine-N-oxide (721 mg, 6.158 mmol). The reaction was
stirred for 30 h at room temperature and evaporated to give a
black oil that was purified by column chromatography (80-
100% EtOAc/petrol) to give compound 8 as a white foamy solid
(1.46 g, 88%). Rf 0.07 (50% EtOAc/petrol); [R]25 +20 (c 4.6,
11: Rf 0.60 (30% EtOAc/petrol); [R]22 -11 (c 0.7, CHCl3); MS
D
D
CHCl3). MS (ES + ve) m/z 588 (M + Na+, 26%); HRMS (ES +
ve) calcd for C32H39NO8Na (M + Na+) 588.2541, found 588.2545.
1H NMR (300 MHz, CDCl3) δ 7.40-7.38 (m, 15H, Ar), 4.27-
4.20 (m, 1H, H4), 4.16-4.07 (m, 1H, H3), 3.88-3.83 (m, 1H,
H2′) 3.81-3.76 (m, 1H, H3′), 3.74-3.69 (m, 1H, H1′), 3.37-
3.29 (m, 3H, H2, H4′, H5), 3.10-3.05 (m, 1H, H5), 1.39 (s, 9H,
tBu); 13C NMR δ 157.3 (CO), 143.7 (C), 128.6 (2 × CH), 127.8
(2 × CH), 127.0 (CH), 86.5 (C), 81.0 (C), 73.3 (CH), 72.6 (CH),
72.5 (CH), 69.9 (CH), 69.0 (CH), 65.1 (CH), 63.9 (CH2), 51.2
(CH2), 28.3 (CH3).
(CI + ve) m/z 656 (M + H+, 5%); HRMS (ES + ve) calcd for
C
43H46NO5 (M + H+) 656.3375, found 656.3367. 1H NMR (300
MHz, CDCl3) δ 7.33-7.20 (m, 25H, Ar), 4.93 (d, 1H, J ) 10.8
Hz, CH2Ph), 4.89 (d, 1H, J ) 11.7 Hz, CH2Ph), 4.81 (d, 1H, J
) 10.8 Hz, CH2Ph), 4.72 (d, 1H, J ) 11.1 Hz, CH2Ph), 4.66-
4.51 (m, 6H, CH2Ph), 3.99 (app. q, 1H, J ) 7.2 Hz, H2), 3.80
(dd, 1H, J ) 6.9, 5.7 Hz, H1), 3.65-3.60 (m, 1H, H6), 3.58
3.53 (m, 1H, H7), 3.35 (dd, 1H, J ) 9.3, 8.4 Hz, H8), 3.22-
3.18 (m, 1H, H3), 3.17-3.13 (m, 1H, H5), 2.57-2.54 (m, 1H,
H8a), 2.53-2.49 (m, 1H, H3), 2.20 (t, 1H, J ) 10.2 Hz, H5);
13C NMR δ 138.7 (C), 138.5 (C), 138.3 (C), 138.2 (C), 138.0 (C),
128.4 (CH), 128.3 (2 × CH), 128.2 (CH), 128.1 (CH), 128.0 (CH),
127.8 (3 × CH), 127.7 (CH), 127.6 (CH), 127.5 (CH), 127.4 (CH),
127.3 (CH), 87.1 (CH), 81.6 (CH), 80.2 (CH), 79.0 (CH), 76.0
(CH), 75.7 (CH2), 74.3 (CH2), 72.8 (CH2), 72.2 (CH2), 72.0 (CH2),
70.3 (CH), 57.1 (CH2), 53.5 (CH2).
ter t-Bu t yl (2S,3S,4R)-3,4-Bis(b en zyloxy)-2-[(2R,3R)-
1,2,3-tr is(ben zyloxy)-4-tr ip h en ylm eth yloxybu tyl]p yr r ol-
id in e-1-ca r boxyla te (9). To a solution of the pentaol 8 (2.25
g, 3.989 mmol) in anhydrous THF (20 mL) at 0 °C was added
50% NaH in mineral oil (1.053 g, 21.94 mmol). After H2
evolution had ceased (10 min), benzyl bromide (4.75 mL, 39.89
mmol) and tetrabutylammonium iodide (147 mg, 0.399 mmol)
were added. The mixture was brought to 50 °C and stirred for
3 d, then cooled to room temperature, treated with methanol
(5 mL) and triethylamine (3 mL), and stirred for 10 min. All
volatiles were removed in vacuo and the residue was dissolved
in diethyl ether, filtered through Celite, followed by further
washings of the solids with diethyl ether. The solvent was
removed in vacuo and the residue was purified by column
chromatography (5-30% EtOAc/petrol) to give compound 9 as
(1S,2R,6S,7R,8R,8a R)-Oct a h yd r oin d olizin e-1,2,6,7,8-
p en tol (1). To a solution of 11 (460 mg, 0.702 mmol) in EtOAc
(4 mL) and MeOH (3 mL) was added palladium chloride (187
mg, 1.053 mmol). The mixture was stirred at room tempera-
ture under an atmosphere of hydrogen (1 atm) for 18 h. The
mixture was filtered through Celite and the solids were
washed with methanol. The combined filtrates were evapo-
rated in vacuo and the residue was dissolved in water and
applied to a column of Amberlyst (OH-) A-26 resin. Elution
with water followed by evaporation in vacuo resulted in a
cloudy white residue that was recrystallized from boiling EtOH
with a few drops of H2O to give compound 1 (90 mg, 63%) as
a brown oil (3.08 g, 76%). Rf 0.65 (10% EtOAc/petrol); [R]23
D
+14 (c 3.5, CHCl3); MS (ES + ve) m/z 1016 (M + H+, 33%);
HRMS (ES + ve) calcd for C67H70NO8 (M + H+) 1016.5101,
found 1016.5113. 1H NMR (500 MHz, CDCl3) δ 7.44-6.69 (m,
40H, Ar), 4.80-4.40 (m, 10H, CH2Ph), 4.40-3.26 (m, 10H, H2-
H5, H1′-H4′), 1.43 (s, 9H, tBu); 13C NMR (125 MHz) δ (major
rotamer) 154.3 (CO), 143.9 (C), 138.7 (C), 138.6 (C), 138.3 (C),
138.0 (C), 137.8 (C), 128.8 (CH), 128.7 (CH), 128.2 (CH), 128.14
(CH), 128.10 (CH), 128.0 (CH), 127.9 (CH), 127.8 (CH), 127.4
(CH), 127.3 (CH), 127.2 (CH), 126.8 (CH), 86.9 (C), 80.0 (C),
79.9 (CH), 79.1 (CH), 78.0 (CH), 77.4 (CH), 76.9 (CH), 75.7
(CH), 75.1 (CH), 74.6 (CH2), 73.7 (CH2), 72.5 (CH2), 71.7 (CH2),
64.0 (CH), 63.8 (CH2), 48.7 (CH2).
colorless microcrystals, mp 170-172 °C. [R]25 -10 (c 0.67,
D
MeOH); [R]25D -6 (c 5.0, H2O); MS (CI + ve) m/z 206 (M + H+,
100%); HRMS (CI + ve) calcd for C8H15NO5 205.0950, found
205.0947; 1H NMR refer to Table 1; 13C NMR (D2O) δ 79.1
(CH), 74.1 (CH), 73.9 (CH), 70.5 (CH), 70.4 (CH), 68.6 (CH),
59.2 (CH2), 55.4 (CH2).
(1S,2R,6S,7R,8R,8a R)-Oct a h yd r oin d olizin e-1,2,6,7,8-
p en tylp en ta a ceta te (12). To a solution of 1 (38 mg, 0.185
mmol) in anhydrous pyridine (0.75 mL, 9.268 mmol) was added
acetic anhydride (0.87 mL, 9.268 mmol) and N,N-(dimethyl-
amino)pyridine (ca.. 2 crystals). The mixture was stirred at
room temperature for 4 h followed by the evaporation of all
volatiles in vacuo. The oily residue was purified by column
chromatography (40-60% EtOAc/petrol and 100% EtOAc) and
recrystallized (boiling petrol with a few drops of EtOAc) to give
the pentaacetate 12 (68 mg, 88%) as colorless crystals, mp 142
°C. Rf 0.34 (40% EtOAc/petrol); [R]21D -15 (c 1.36, CHCl3); MS
(CI + ve) m/z 416 (M + H+, 87%); HRMS (ES + ve) calcd for
(2S,3S)-4-[(2R,3S,4R)-3,4-Diben zyloxyp yr r olid in -2-yl]-
2,3,4-tr iben zyloxybu ta n -1-ol (10) a n d (1S,2R,6S,7R,8R,-
8a R)-1,2,6,7,8-P en t a b en yloxyoct a h yd r oin d olizin e (11).
To a solution of 9 (774 mg, 0.763 mmol) in anhydrous DCM (7
mL) at 0 °C was added anisole (0.83 mL, 7.626 mmol) and
trifluoroacetic acid (5.87 mL, 76.26 mmol). The mixture was
stirred at 0 °C for 2 h, followed by the evaporation of all
volatiles in vacuo. The residue was dissolved in DCM (15 mL)
and washed with saturated Na2CO3 solution (20 mL). The
aqueous layer was extracted with DCM (2 × 15 mL). The
combined DCM layers were dried (MgSO4) and evaporated to
give a brown oil that was purified by column chromatography
(40-100% EtOAc/petrol and 20% MeOH/EtOAc) to give com-
C
18H26NO10 416.1557, found 416.1573. 1H NMR (500 MHz,
CDCl3) δ 5.25 (q, 1H, J 1,2 ) J 2,3R ) J 2,3â ) 6.3 Hz, H2), 5.11 (t,
1H, J 6,7 ) J 7,8 ) 9.3 Hz, H7), 5.02 (t, 1H, J 1,2 ) J 1,8a ) 7.3 Hz,
H1), 4.97 (dd, 1H, J 5â,6 ) 5.8 Hz, J 5R,6 ) 9.8 Hz, H6), 4.96 (t,
3142 J . Org. Chem., Vol. 69, No. 9, 2004