8078
P.L. Katavic et al. / Tetrahedron 69 (2013) 8074e8079
completely dissolved. After stirring under argon for 20 h at room
temperature, the solvent was removed under reduced pressure
4.6.1. 2-Acetamido-1,6-anhydro-2-deoxy-3-O-[(1S)-1-(methox-
ycarbonyl)ethyl]- -glucopyranose (15). Amorphous white solid;
ꢀ38 (c 0.013, CHCl3); dH (500 MHz, CDCl3) 1.42 (d, 6.9, 3H,
b-D
and the syrupy
trile to yield a white solid.
D
-glucal (8) was twice evaporated from acetoni-
-Glucal was suspended in dry aceto-
[a]
D
D
CH3CH), 1.99 (s, 3H, Ac), 3.34 (m, 1H, H3), 3.73 (s, 3H, OMe), 3.76 (m,
1H, H6b), 3.96e3.99 (m, 2H, H2, H4), 4.28 (dd, 0.8, 5.5, 1H, H6a),
4.30 (q, 7.0,1H, CHCH3), 4.52 (d, 5.7,1H, H5), 5.35 (s,1H, H1), 6.07 (d,
9.4, 1H, NH); dC (125 MHz, CDCl3) 18.5 (CH3CH), 23.1 (Ac), 48.2 (C2),
51.9 (OMe), 64.8 (C6), 70.0 (C4), 73.5 (CHCH3), 75.7 (C5), 78.9 (C3),
100.5 (C1), 169.7 (Ac), 173.8 (COOMe); HRMS (ESI): [MþNa]þ, found
312.1056. C12H19NNaO7 requires 312.1054.
ꢀ
nitrile (10 mL) and stirred over activated 3 A molecular sieves for
30 min before bis(tributyl)tin oxide (0.94 mmol) was added and
the mixture refluxed for 3.5 h under argon. The reaction mixture
was allowed to cool and I2 (1.76 mmol) was added and the mix-
ture stirred for 16 h under argon at room temperature. The re-
action mixture was filtered through Celite under vacuum and the
filtrate was concentrated under reduced pressure. The residue was
partitioned between aq sodium thiosulfate solution (5 g/50 mL)
and hexane (75 mL). The aqueous phase was extracted with EtOAc
(3ꢂ75 mL). The EtOAc phases were combined, dried over MgSO4,
4.7. Procedure for esterification of 14 and 15
Anhydrosugars 14 and 15 were dissolved in dry DCM (1.5 mL)
and palmitic acid (1.3 equiv), DCC (1.3 equiv) and DMAP (0.7 mg)
were stirred under nitrogen for 3 h at room temperature. DCM was
evaporated and the residue suspended in ether (5 mL) and filtered
through a small pad of Celite. The filtrate was evaporated and the
residue chromatographed on silica gel (stepwise gradient, hexane
to 40% EtOAc) to yield palmitate esters 3 and 4.
filtered, and evaporated to yield 1,6-anhydro-2-deoxy-2-iodo-b-D-
glucopyranose (9),7 which was used without any further purifi-
cation or characterization. Following evaporation twice from
acetonitrile, 9 was dissolved in anhydrous DMF and stirred in
a three-necked flask under argon at ꢀ20 ꢁC. Benzyl bromide
(3.51 mmol) was added, followed by NaH (60% dispersion in
mineral oil, 3.51 mmol) and the reaction mixture was allowed to
slowly warm to room temperature over 2 h.9 MeOH (1.5 mL) was
added, followed by H2O (1.5 mL) and EtOAc (30 mL), and the or-
ganic phase was extracted with H2O (3ꢂ50 mL). The EtOAc phase
was dried over MgSO4, filtered and evaporated and partitioned
between MeOH (30 mL) and hexane (3ꢂ30 mL). The MeOH phase
4.7.1. 2-Acetamido-1,6-anhydro-2-deoxy-3-O-[(1R)-1-(methox-
ycarbonyl)ethyl]-4-O-palmitoyl-
white solid; [
b-D-glucopyranose (3). Amorphous
ꢀ14 (c 0.045, CHCl3); dH (500 MHz, CDCl3) see
a]
D
Table 1; dC (125 MHz, CDCl3) 13.7 (C160), 18.2 (C300), 22.0e32.0 (C40-
C150, 12C), 23.0 (NHCOCH3), 25.0 (C30), 33.4 (C20), 50.4 (C2), 51.9
(OMe), 65.5 (C6), 71.9 (C4), 73.7 (C5), 74.5 (C100), 76.0 (C3), 100.8
(C1), 169.4 (NHCOCH3), 173.3 (C200), 176.0 (C10); HRMS (ESI):
[MþNa]þ, found 550.3351. C28H49NNaO8 requires 550.3350.
was evaporated to yield 4-O-benzyl-1,6:2,3-dianhydro-b-D-glu-
copyranose (10). The 1H NMR spectrum of 10 was consistent with
the literature spectrum4 and was used without any further puri-
fication or characterization. Sodium azide (4.39 mmol) was dis-
solved in H2O (0.2 mL) and added to a stirring solution of 10 in
DMF (1.8 mL) and heated to 105 ꢁC for 20 h. The reaction mixture
was diluted with EtOAc (30 mL) and extracted with H2O
(3ꢂ50 mL) and the organic phase was dried over dried over
MgSO4, filtered and evaporated. The residue was chromato-
graphed over silica gel (stepwise gradient, hexane to 30% EtOAc)
to yield the desired azide (11) (35.6 mg, 10% yield over five steps).
The 1H NMR spectrum of 11 was consistent with the literature
spectrum.4
4.7.2. 2-Acetamido-1,6-anhydro-2-deoxy-3-O-[(1S)-1-(methox-
ycarbonyl)ethyl]-4-O-palmitoyl-
white solid; [
b-D-glucopyranose (4). Amorphous
D ꢀ43 (c 0.08, CHCl3); dH (500 MHz, CDCl3) see Table
a
]
1; dC (125 MHz, CDCl3) 13.7 (C160), 18.5 (C300), 22.0e32.0 (C40-C150,
12C), 23.2 (NHCOCH3), 25.0 (C30), 33.8 (C20), 48.5 (C2), 51.9 (OMe),
64.8 (C6), 70.3 (C4), 73.5 (C5), 74.2 (C100), 76.8 (C3), 100.6 (Cþ1), 169.2
(NHCOCH3), 173.3 (C200), 176.3 (C10); HRMS (ESI): [MþNa] , found
550.3361. C28H49NNaO8 requires 550.3350.
Acknowledgements
4.5. 1,6-Anhydro-2-azido-4-O-benzyl-2-deoxy-3-O-[(1S)-1-
We thank the Australian Research Council and The University of
Queensland for financial support. In vitro anti-inflammatory and
cytotoxicity assays were carried out by Ms. Kellie M. Shepherd. We
thank Mr. Graham Macfarlane for acquiring HRMS, and Assoc. Prof.
Ross McGeary for his interest in the manuscript. Sponge collection
was made with assistance of staff of ScubaWorld, Mooloolaba.
(methoxycarbonyl)ethyl]-
anhydro-2-azido-4-O-benzyl-2-deoxy-3-O-[(1R)-1-(methox-
ycarbonyl)ethyl]- -glucopyranose (13)
b-D-glucopyranose (12) and 1,6-
b-D
NaH (60% dispersion in mineral oil, 2.4 mmol) was added in one
portion to a stirring solution of 11 (0.4 mmol, 11.2 mg) and
(þ)-methyl (R)-2-chloropropionate (1.2 mmol) in anhydrous DMF
(1 mL) and stirred at 105 ꢁC for 16 h. The reaction mixture was
diluted with EtOAc (40 mL) and extracted with H2O (3ꢂ50 mL). The
organic phase was dried over MgSO4, filtered and evaporated and
chromatographed over silica gel (9:1 hexane/EtOAc) to yield the
desired ethers (12) (3.8 mg) and (13) (2.6 mg) and a 1:1 mixture of
12 and 13 (4.8 mg). The 1H NMR spectra of 12 and 13 were con-
sistent with literature data.10
Supplementary data
Supplementary data associated with this article can be found in
References and notes
4.6. Procedure for hydrogenation and acetylation of 12 and 13
Benzyl protected azido anhydrosugars 12 and 13 were stirred for
16 h under an atmosphere of H2 in MeOH (1.5 mL) with Ac2O
(1.2 equiv) and 1e2 mg of 10% palladium on activated carbon. Fil-
tration through Celite and silica gel chromatography (60:39:1
hexane/EtOAc/MeOH) yielded the C-4 alcohols 14 and 15. The 1H
NMR spectrum and optical rotation of 14 were consistent with
ꢁ
literature data ([
a
]
D ꢀ26.8 (c 0.033, CHCl3), lit. ꢀ27).10