602
C. Leimkuhler et al. / Tetrahedron: Asymmetry 16 (2005) 599–603
(250 · 50 mm) or on a Hitachi L6200 instrument (flow-
rate: 7.5 mL/min) using a Phenomenex Luna 5 lm C18
column (250 · 21.2 mm). NMR spectra were recorded
on Varian Mercury 300 MHz andInova 400 or
500 MHz spectrometers. Low resolution mass spectra
(ESI) were obtainedat Princeton University. High-reso-
lution mass spectra (HRMS) were obtainedat the Uni-
versity of California at Riverside Department of
Chemistry Mass Spectrometry Facility.
60% purity, 0.12 mmol). The reaction was slowly
warmedto ꢀ20 ꢁC over 45 min andkept at ꢀ20 ꢁC for
15 min before being quenchedwith Me 2S (1.0 mL).
The reaction was extractedwith satdaq NaHCO solu-
3
tion, andthe aqueous layer was further extractedwith
CH2Cl2 (3 · 50 mL). The organic layers were combined,
dried (MgSO4), filteredandconcentratedto a colorless
oil. The oil was purifiedby flash chromatography
(60% EtOAc/petroleum ether) to give sulfoxide 3
(435 mg, 96%) as a white solid. Rf (60% EtOAc/petro-
leum ether): 0.25–0.35. LRMS (ESI): calculated(M +
Na, C18H23NO6SNa) 404; found404.
4.2. Phenyl 3-allyloxycarbonylamino-4-O-acetyl-2,3,6-
trideoxy-1-thio-a,b-L-lyxo-hexopyranoside 9
To a solution of thioglycoside 7 (770 mg, 2.5 mmol) in
MeOH (20 mL) was added K2CO3 (380 mg, 1.25 mmol).
After stirring for 8 h, the solution was pouredinto satd
4.4. Protected desmethyl vancomycin 4
The pseudoaglycone 2 (808 mg, 0.459 mmol) was azeo-
tropedwith toluene (3 · 1 mL), dissolved in CH2Cl2
aq NH4Cl, which was extractedwith CH Cl2 (3·). The
2
organic layers were washedwith brine, dried(MgSO 4),
filteredandevaporatedto give phenyl 3-azido-2,3,6-tri-
deoxy-1-thio-a,b-L-lyxo-hexopyranoside (660 mg, quant.)
as a colorless syrup.
(20 mL) andcooledto
ꢀ78 ꢁC. BF3ÆOEt2 (113 lL,
0.918 mmol) was added followed by triflic anhydride
(77.2 lL, 0.122 mmol). A solution of the sulfoxide 3
(315 mg, 0.826 mmol) in a mixture of CH2Cl2 (6 mL)
andEt O (8 mL) was added to the reaction dropwise
2
This compound(660 mg, 0.25 mmol) was dissolvedin
(1.3 g, 5.0 mmol)
over 15 min. The reaction was allowedto warm up to
ꢀ10 ꢁC over 1 h andthen quenchedwith a mixture of
methanol (400 lL) andDIPEA (400 lL). The solvents
were evaporatedandthe residue was purifiedby flash
chromatography (gradient 2.5–4% MeOH/CH2Cl2) to
THF/H2O (40 mL, 10:1) andPPh
3
was added. The reaction was stirred at 60 ꢁC for 2 h
and cooled to room temperature. After the addition of
a solution of Alloc succinimide (740 mg, 3.7 mmol) in
THF (20 mL), the reaction was stirredat room tempera-
ture for 3 h, concentratedandpurifiedby flash chroma-
tography (15% EtOAc/CH2Cl2) to give phenyl 3-
allyloxycarbonylamino-2,3,6-trideoxy-1-thio-a,b-L-lyxo-
hexopyranoside (770 mg, 96%) as a colorless oil. Rf (15%
EtOAc/petroleum ether): 0.25 (a-anomer), 0.30 (b-ano-
mer). To a solution of this compound(770 mg, 2.4 mmol)
in CH2Cl2 (30 mL) was added triethylamine (1.33 mL,
9.5 mmol) followedby acetic anhyrdied (0.45 mL,
4.8 mmol) andDMAP (58 mg, 0.48 mmol). The reaction
was stirredat room temperature for 1 h andwas
quenchedwith methanol. The reaction mixture was evap-
oratedandpurifiedby flash chromatography (10%
EtOAc/CH2Cl2) to give thioglycoside 9 (840 mg, 97%)
as a white solid. Rf (10% EtOAc/CH2Cl2): 0.35 (a-ano-
mer), 0.39 (b-anomer). Compound 9a: 1H NMR (CDCl3,
500 MHz): d = 7.51–7.23 (m, 5H, ArH), 5.92 (m, 1H,
allyl-H), 5.71 (d, J1,2 = 5.5 Hz, 1H, H-1), 5.31 (br d,
J = 17.5 Hz, 1H, allyl-H), 5.24 (br d, J = 10.5 Hz, allyl-
H, 5.20 (s, 1H, H-4), 4.87 (br d, J = 7.6 Hz, 1H, NH),
4.55 (q, J5,6 = 6.3 Hz, 1H, H-5), 4.29 (br m, 1H, H-3)
affordthe protecteddesmethyl vancomycin
4 (608 mg,
66%) as a white solid. Rf (5% MeOH/CH2Cl2): 0.28.
HRMS (FAB) calculated(M + Na, C 97H109Cl2N9O34Na)
2036.6352; found2036.6319.
4.5. Desmethyl vancomycin 5
4.5.1. Deprotection of 4. The protected 4 (392 mg,
0.194 mmol) was dissolved in a solution of 3% hydrazine
in allyl alcohol/MeOH (15 mL, 1:2). The reaction was
stirredat room temperature for 24 h andthen quenched
by the addition of acetic acid (2 mL). The solution was
concentratedto a slurry andidlutedwith butanol
(30 mL), which was extractedwith water andaq NH 4Cl
solution (3 · 25 mL). The butanol layer was concen-
tratedto a white solidandpurifiedby flash chromato-
graphy (gradient 12–16% MeOH/CH2Cl2) to give the
deacetylated glycopeptide (182 mg, 53%) as a white
solid. Rf (20% MeOH/CH2Cl2): 0.29. 1H NMR
(CD3OD, 500 MHz): see supporting information. HRMS
0
2.25 (ddd, J1,2 = 5.5 Hz, J2,3 = 13.0 Hz, J2,2 = 13.5 Hz,
1H, H-2), 2.18 (s, 3H, Ac-H), 2.10 (br dd, J2,3 = 4.4 Hz,
(FAB): calculated(M + Na,
1784.5718; found1784.5664.
C
85H97Cl2N9O28Na)
J2,2 = 13.5 Hz, 1H, H-20), 1.12 (d, J5,6 = 6.3 Hz, 3H,
0
CH3-6). 13C NMR (CDCl3, 500 MHz): d = 171.4, 155.9,
135.5, 133.4, 131.8, 129.7, 127.8, 118.8, 84.5, 71.8,
66.9, 66.6, 47.4, 32.4, 21.5, 17.6; HRMS (FAB): calcu-
To a solution of this compound(160 mg, 91 lmol) in
DMF/acetic acid (4.0 mL, 1:1) was added PdCl2(PPh3)2
(25.5 mg, 31 lmol). The reaction was degassed and put
under argon. To this mixture was added Bu3SnH
(2.5 mL) in 100 lL portions every 5 min until all the
material had been added. The crude reaction mixture
was precipitatedin acetone (80 mL). The mixture was
centrifuged and decanted to give a white solid, which
was suspended in water (5 mL) and kept at 4 ꢁC over-
night. The suspension was filteredandthe filtrate was
concentratedandpurifiedby reverse-dphase HPLC
lated(M + Na,
388.1184.
C 18H23NO5SNa) 388.1195; found
4.3. Phenyl 3-allyloxycarbonylamino-4-O-acetyl-2,3,6-
trideoxy-1-sulfinyl-a,b-L-lyxo-hexopyranoside 3
To a solution of thioglycoside 9 (440 mg, 0.12 mmol) in
CH2Cl2 (30 mL) at ꢀ70 ꢁC was added mCPBA (345 mg,