Design and synthesis of oxazolidinone ketolide antibiotic segment mimetics

Article abstract of DOI:10.1139/v05-095

Macrolides have been modified to a large extent by structural and functional variants to expand their spectrum of activity and overcome resistance. Ketolides are new generation 14-membered ring macrolides derived by chemical modification of the readily av

Full text of DOI:10.1139/v05-095

801
Design and synthesis of oxazolidinone ketolide
antibiotic segment mimetics1
Stephen Hanessian and Kiran Kumar Kothakonda
Abstract: Macrolides have been modified to a large extent by structural and functional variants to expand their spec-
trum of activity and overcome resistance. Ketolides are new generation 14-membered ring macrolides derived by chem-
ical modification of the readily available erythromycin A. We have designed and synthesized bicyclic oxazolidinone-δ-
lactones to mimic the “left segment” periphery of ketolides.
Key words: macrolide, ketolide, 50S r-RNA, segment mimetics.
Résumé : Des macrolides ont été beaucoup modifiés par des variations de structure et de fonction afin d’élargir leur
spectre d’activité et pour vaincre la résistance. Les cétolides correspondent à une nouvelle génération de macrolides à
quatorze chaînons qui dérivent de modifications chimiques de l’érythromycine A qui est facilement accessible. Pour
imiter le segment de gauche de la périphérie des cétolides, de nouvelles δ-lactones bicycliques de l’oxazolidinone ont
été développées et synthétisées.
Mots clés : macrolide, cétolide, 50S r-ARN, imitation d’un segment.
[Traduit par la Rédaction] Hanessian and Kothakonda 811
Introduction
ants such as flurithromycin, roxitromycin, and dirithromycin
(8). More recently, a new class of potent antibiotics called
ketolides as exemplified by telithromycin (HMR-3647) (4)
(9) and cethromycin (ABT-773) (5) (10), was discovered
(Fig. 1). These macrolide structures are derived from ery-
thromycin via substantial functional modification, notably
the omission of cladinose, the presence of a carbonyl group
at C-3, and an oxazolidinone ring at the C-11 and (or) C-12.
The presence of heterocyclic side-chain appendages on the
oxazolidinones greatly enhances the antibacterial profile.
Ketolides were found to be active against penicillin-resistant
and erythromycin resistant S. pneumoniae, hence, their great
potential as a new generation of macrolide antibiotics tar-
geted to the resistant organisms.
Macrolide antibiotics exert their antibacterial action by
stimulating the dissociation of peptidyl t-RNA from the bac-
terial ribosome during the translocation process, thereby in-
hibiting protein synthesis. They bind to the 2058–2062
region of 23S ribosomal RNA of the 50S ribosomal subunit
in the vicinity of peptide exit channel (11).
Macrolides have been used as effective antibiotics to com-
bat infection caused by various Gram-positive bacteria such
as Staphylococcus aureus, Streptococcus pneumoniae, and
Streptococcus pyogenes for over 50 years (1). The discovery
of the 14-membered macrolide erythromycin (1) (2) was a
major breakthrough in antimicrobial research, exhibiting ac-
tivity against penicillin-resistant S. aureus. Erythromycin has
been widely prescribed for the treatment of upper and lower
respiratory tract infections in children because of its excel-
lent record of safety. However, the main disadvantage of
erythromycin is its instability in the acidic medium in the
stomach, which results in degradation (3). The semisynthetic
macrolides such as clarithromycin (2) (4) and azithromycin
(3) (5) are stable in acidic medium and also possess activity
against Haemophilus influenzae, among other pathogenic or-
ganisms. Unfortunately, erythromycin, clarithromycin, and
azithromycin are ineffective against organisms that show
macrolide – lincosamide – streptogramin B (MLSB) cross-
resistance (6). As a result of extensive research aimed at dis-
covering new analogues (7), erythromycin has been replaced
to a large extent by structural and chemically modified vari-
Results and discussion
Design
Received 1 December 2004. Published on the NRC Research
Press Web site at http://canjchem.nrc.ca on 2 July 2005.
As part of a research program aimed at new antibacterial
RNA-binding small molecules (12, 13), we were interested
in studying the functional role of the oxazolidinone subunit
spanning C-11 and C-12 in the ketolides. Recently available
X-ray data on ketolides (14), and classical X-ray structural
(15), and NMR studies (16) on erythromycin many years
ago, have revealed the prevalence of a unique three-
dimensional, crown-like conformation with the edges of hy-
pothetical chair-like cyclohexanes (Fig. 2). A better visual-
ization of the topology of 14-membered macrolides can be
considered in conjunction with a virtual diamond lattice
Dedicated to Professor Howard Alper, wishing him the best
in chemistry and in life.
S. Hanessian2 and K.K. Kothakonda. Department of
Chemistry, University of Montreal, P.O. Box 6128, Station
Centre-Ville, Montreal, QC H3C 3J7, Canada.
1This article is part of a Special Issue dedicated to Professor
Howard Alper.
2Corresponding author (e-mail:
stephen.hanessian@umontreal.ca).
Can. J. Chem. 83: 801–811 (2005)
doi: 10.1139/V05-095
© 2005 NRC Canada

802
Can. J. Chem. Vol. 83, 2005
Fig. 1. Structure of macrolide antibiotics.
O
N
9
11
HO
OR
O
HO
OH
O
OH
OH
6
OH
OH
13
O
N
O
N
2
O
O
O
O
O
O
O
O
MeO
MeO
OH
OH
Azithromycin (3)
R = H, Erythromycin (1)
R = Me, Clarithromycin (2)
N
N
N
O
N
O
H
N
O
O
N
O
O
O
O
OMe
OH
O
OH
O
N
O
O
N
O
O
O
O
O
Cethromycin (5)
Telithromycin (4)
O
N
F
O
N
O
Linezolid
NHAc
heterocyclic side-chain appendages similar to those found in
the ketolides, would prove to be an asset (18).
Fig. 2. Design of cis- and trans-oxazolidinone segment mimetics.
O
OH
OH
OH
OH
HO
Synthesis
O
O
The synthesis of cis- and (or) trans-oxazolidinone-δ-lac-
tones started from methyl 2-deoxy-4,6-O-benzylidene-α-D-
ribo-hexopyranoside (6), which is readily obtained from
methyl α-D-glucopyranoside (19) (Scheme 1). Regioselective
reductive ring opening of the benzylidene acetal was
achieved in an 85:15 ratio using LAH–AlCl3 to afford 7 in
77% yield (20). Selective protection of the primary hydroxyl
group with tosyl chloride gave 8, which was treated with
Me2CuLi at –78 °C to afford the chain-extended analogue 9.
There are few reported examples of cuprate-mediated
functionalizations of the terminal carbon atoms in the sugar
series (21).
To obtain the trans-oxazolidinones, the mesylate 10 was
treated with NaN3 in refluxing DMF to give the azido ana-
logue 11 in 80% yield. Treatment with Me3P in THF under
Staudinger (22) conditions reduced the azide to the amine,
which was then subjected to reductive amination with two
aldehydes using NaCNBH3–AcOH in MeOH, giving 12a
and 12b in good yields. Benzyl deprotection was achieved
with 10% Pd(OH)2-on-carbon in EtOAc under a hydrogen
Erythromycin aglycon
Virtual diamond lattice
O
R
N
O
R
O
O
O
O
N
O
N
O
O
O
O
O
O
O
N
R
O
O
O
R
Bicyclic
lactone
Ketolide
substructure
A (cis-)
B (trans-)
(17). We therefore hypothesized that bicyclic cis- and trans-
oxazolidinone-δ-lactones represented by structures A and B
could simulate the minimal spatial requirements of the keto-
lides “western” landscape, by occupying a corresponding re-
gion of the lattice. Although the proposed prototypes were
substantially different in overall topology, and lacked the
all-important desosamine sugar, compared with the keto-
lides, they shared a common oxazolidinone subunit. It was
surmised that the diversification at nitrogen with a variety of
© 2005 NRC Canada

Hanessian and Kothakonda
803
Scheme 1. Reagents and conditions: (a) LAH, AlCl3, CH2Cl2, ether, reflux, 2.5 h; (b) TsCl, pyridine, CH2Cl2, 16 h; (c) Me2CuLi,
ether, –78 °C to rt, 3 h; (d) MsCl, pyridine, 12 h; (e) NaN3, DMF, 160 °C, 1.5 h; ( f ) (i) Me3P, THF, H2O, reflux, 40 min; (ii) R-
CHO, MeOH, AcOH, NaCNBH3, 12 h; (g) H2, 10% Pd(OH)2-C, EtOH, 14 h; (h) CDI, Et3N, CH2Cl2, 5 h; (i) 6 N HCl, dioxane, 1 h;
( j ) PCC, 4 Å molecular sieves, CH2Cl2, 4 h.
a
O
O
HO
BnO
TsO
BnO
b
c
O
O
O
O
Ph
BnO
(77%)
(80%)
(89%)
OH OMe
6
OH OMe
7
OH OMe
8
OH OMe
9
g
e
f
d
O
O
O
OMe
BnO
BnO
BnO
N3
HN
(94%)
(80%)
OMs OMe
10
OMe
R
11
12a,12b
j
h
i
O
O
O
O
HO
HN
O
O
O
N
N
N
O
O
O
O
OMe
13a,13b
OMe
14a,14b
OH
15a,15b
R
R
R
R
16a,16b
a) R = Ph(CH2)2 b) R = CH3(CH2)5
atmosphere to obtain 13a and 13b. Treatment with carbonyl
diimidazole (23) in Et3N gave the required oxazolidinones
14a and 14b. Hydrolysis of the glycosides in 6 N HCl –
dioxane gave the hemiacetals 15a and 15b, which were oxi-
dized with PCC to afford the desired target trans-
oxazolidinone lactones 16a and 16b in good yields.
points with the RNA targets, without alternative compensa-
tory binding. Such an outcome was not entirely unexpected,
given the drastic departure from the traditional macrolide
structure, including the omission of the desosamine glyco-
side. Nevertheless, it was hoped that the minimal oxazoli-
dinone motif, harboring an optimized heterocyclic side-chain
appendage (as in 27e) would contribute to a modest level of
inhibition of bacterial growth. In this context, it is of interest
that simple, N-aryl oxazolidinones such as linezolid (Fig. 1)
have emerged as a new generation of antibacterial agents
(26).
In conclusion, we have synthesized a series of bicyclic δ-
lactone oxazolidinones as segment mimetics of ketolides.
Their lack of inhibitory activity in vitro emphasizes the im-
portance of the macrolide structure and the desosamine unit
for achieving effective binding to bacterial ribosomes.
The cis-oxazolidinones were prepared from the common
intermediate 9 (Scheme 2). Thus, a Mitsunobu reaction with
p-nitrobenzoic acid gave the inverted ester 17 in 78% yield
(24). Saponification gave 18, which was mesylated to give
19 and the latter was treated with catalytic 10% Pd-on-
carbon under a hydrogen atmosphere affording 20. Nucleo-
philic displacement with NaN3 in DMF led to 21, which was
converted to PMB 22. Reduction under Staudinger condi-
tions (22) reduced the azide to the amine, which was sub-
jected to reductive amination with various aldehydes using
NaCNBH3–AcOH in MeOH to obtain the corresponding
amines (23a–23e) in good yields. The PMB ether group was
cleaved with ceric ammonium nitrate to obtain 24a–24e.
Treatment of the cis-amino alcohols with carbonyl diimid-
azole (23) in Et3N gave the intended oxazolidinones 25a–
25e. Cleavage of the glycosides in 6 N HCl – dioxane led to
the hemiacetals 26a–26e, which, upon oxidation with PCC,
gave the cis-oxazolidinone lactones 27a–27e in good yields.
Single crystal X-ray structure analysis of 27a and 27c con-
firmed the stereochemistry of the cis-oxazolidinone ring.3
The bicyclic oxazolidinone lactones 16a and 16b and
27a–27e did not inhibit the growth of S. aureus at minimum
inhibitory concentrations of >50 µg/mL (25). Lack of inhibi-
tion in the macrolide series is generally attributed to cell
penetration, efflux, resistance, and ineffective binding to the
ribosomal RNA target. It is clear that the simplification of
the macrolide structure of the ketolides to bicyclic lactone
prototypes resulted in the loss of several important contact
Experimental
General procedure
Flash chromatography was carried out using 230–400
mesh silica gel. Mixtures of ethyl acetate and hexanes were
used as the eluents, unless otherwise specified. Analytical
TLC was performed on glass plates coated with a 0.02 mm
layer of silica gel 60 F-254. Melting points were uncor-
1
rected. IR spectra were recorded as films. H and 13C NMR
spectra were recorded at 300 and 400 MHz, respectively,
and the chemical shifts are reported in ppm on the δ scale,
with CDCl3 as the reference, unless otherwise specified. MS
and HR-MS spectra were recorded using electron ionization
or by the FAB technique. Optical rotations were measured in
CHCl3 or MeOH at 23 °C. All reactions were carried out un-
der nitrogen or argon unless otherwise specified. The –78 °C
3 Supplementary data for this article are available on the Web site or may be purchased from the Depository of Unpublished Data, Document
Delivery, CISTI, National Research Council Canada, Ottawa, ON K1A 0S2, Canada. DUD 3690. For more information on obtaining mate-
rial refer to http://cisti-icist.nrc-cnrc.gc.ca/irm/unpub_e.shtml. CCDC 266401 and 266402 contain the crystallographic data for this manu-
script. These data can be obtained, free of charge, via www.ccdc.cam.ac.uk/conts/retrieving.html (Or from the Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax +44 1223 336033; or deposit@ccdc.cam.ac.uk).
© 2005 NRC Canada

804
Can. J. Chem. Vol. 83, 2005
Scheme 2. Reagents and conditions: (a) DIAD, TPP, THF, p-nitro benzoic acid, 12 h; (b) (i) NaOMe, MeOH, rt, 10 h; (ii) MsCl,
pyridine, rt, 12 h; (c) H2, 10% Pd-C, EtOAc, 10 h; (d) (i) NaN3, DMF, 125 °C, 12 h; (ii) PMB-Br, NaH, DMF, 6 h; (e) (i) Me3P,
THF, H2O, reflux, 40 min; (ii) R-CHO, MeOH, AcOH, NaCNBH3, 12 h; ( f ) CAN, AcCN, H2O, 12 h; (g) CDI, Et3N, CH2Cl2, 5 h;
(h) 6 N HCl, dioxane, 1 h; (i) PCC, 4 Å molecular servies, CH2Cl2, 4 h. (Bottom) ORTEP drawing of the X-ray crystal structures of
27a and 27c.
temperature is approximate, as achieved by a dry ice – ace-
tone bath.
98.8, 128.3, 128.9, 138.2. MS calcd. for C14H20NO5: 268.3
(M+); found: 286.2 (M + H2O+).
Methyl 4-O-benzyl-2-deoxy-␣-D-ribo-hexopyranoside (7)
Methyl 4-O-benzyl-2-deoxy-6-O-p-tolylsulfonyl-␣-D-ribo-
hexopyranoside (8)
To
a well-stirred mixture of compound 6 (5 g,
18.8 mmol), lithium aluminium hydride (1.36 g, 35.7 mmol)
in ether (65 mL), and DCM (65 mL) was added aluminium
chloride (3.76 g, 28.2 mmol) under reflux for 15 min and
refluxing was continued for 3 h. The mixture was cooled to
0 °C, quenched with ice, filtered, and washed with EtOAc
(100 mL); the filtrate was washed with brine, dried over
Na2SO4, concentrated under vacuum, and the residue was
purified by column chromatography (EtOAc–hexanes, 1:1)
to give 7 as a thick syrup (3.9 g, 77%). [α]D +205 (c 0.75,
To a solution of compound 7 (3.98 g, 14.85 mmol) in
pyridine (12 mL) and DCM (40 mL) was added p-
toluenesulfonyl chloride (2.92 g, 15.29 mmol) at 0 °C under
an argon atmosphere and the solution was stirred at room
temperature for 16 h. The mixture was concentrated under
vacuum at low temperature, the residue was taken up in
DCM (100 mL), washed with water then with brine, dried
over Na2SO4, concentrated, and purified by column chroma-
tography (EtOAc–hexanes, 3:7) to afford 8 (5 g, 80%). [α]D
+112.7 (c 1, CHCl3). IR (neat, cm–1): 3526. 1H NMR
(400 MHz, CDCl3) δ: 1.82 (m, 1H), 2.15 (dd, 1H, J = 1.7,
15.4 Hz), 2.42 (s, 3H), 3.35 (s, 1H), 3.41 (dd, 1H, (dd, 1H,
J = 1.7, 11.1 Hz)), 4.04 (m, 1H), 4.11 (brm, 1H), 4.22–4.36
(m, 2H), 4.44 (d, 2H, J = 12.5 Hz), 4.75 (m, 1H), 7.22–7.39
(m, 7H), 7.79 (d, 2H, J = 12.1 Hz). 13C NMR (400 MHz,
1
CHCl3). IR (neat, cm–1): 3470. H NMR (400 MHz, CDCl3)
δ: 1.82 (m, 1H), 2.18 (dd, 1H, J = 1.7, 15.4 Hz), 3.38 (s,
1H), 3.42 (dd, 1H, J = 1.7, 11.1 Hz), 3.84 (m, 2H), 3.96 (m,
1H), 4.21 (brm, 1H), 4.56 (d, 2H, J = 12.5 Hz), 4.77, (d, 2H,
J = 12.5 Hz), 4.79 (m, 1H), 7.37 (m, 5H). 13C NMR
(400 MHz, CDCl3) δ: 35.2, 55.6, 62.8, 64.4, 66.8, 70.9, 74.7,
© 2005 NRC Canada

Hanessian and Kothakonda
805
CDCl3) δ: 22.1, 34.9, 55.8, 64.1, 64.9, 70.1, 70.9, 74.0, 98.7,
128.3, 128.9, 130.1, 133.3, 137.7, 145.1.
δ: 10.3, 24.9, 36.0, 54.8, 60.8, 72.3, 75.5, 82.4, 97.6, 128.4,
128.6, 128.9, 139.2.
Methyl 4-O-benzyl-2,6-dideoxy-6-C-methyl-␣-D-ribo-
hexopyranoside (9)
Methyl 4-O-benzyl-6-C-methyl-3-phenylethylamino-
2,3,6-trideoxy-␣-D-arabino-hexopyranoside (12a)
MeLi (45 mL, 1.6 mol/L in Et2O) was added slowly to
CuI (6.77 g, 35.5 mmol) in ether (180 mL) at –20 °C under
an argon atmosphere and stirred at –5 °C for 20 min. Com-
pound 8 (2.5 g, 5.93 mmol) in Et2O (20 mL) was added to
the mixture at –78 °C for 15 min and the mixture was stirred
for 1 h allowing it to warm to 0 °C, then for 3 h at room
temperature. The mixture was quenched with NH4OH and
NH4Cl (1:1, 20 mL), extracted with ether (100 mL), washed
with brine, dried over Na2SO4, and concentrated under vac-
uum. The residue was purified by column chromatography
(EtOAc–hexanes, 2:8) to give compound 9 (1.4 g, 89%).
To a solution of compound 11 (40 mg, 0.137 mmol) in
THF was added trimethylphosphine (0.53 mL, 1 mol/L in to-
luene) and the solution was stirred under an argon atmo-
sphere for 30 min. Water (16 µL) was added to the mixture
and stirred under reflux condition for 45 min. The mixture
was concentrated under vacuum, and the residue was dis-
solved in dry MeOH (3 mL) under an argon atmosphere.
The requisite aldehyde (0.135 mmol) was added followed by
the addition of AcOH (32 µL), and the solution was stirred.
NaCNBH3 (18 mg, 0.274 mmol) was added, the mixture
stirred for 12 h, then concentrated under vacuum. The resi-
due was diluted with EtOAc (10 mL), washed with 10%
NaHCO3 solution and brine, and the organic phase was dried
over Na2SO4, concentrated, and then purification of the resi-
due by column chromatography (EtOAc–hexanes, 2:3) gave
12a (89%). [α]D +53.1 (c 1.85, CHCl3). IR (neat, cm–1):
3825. 1H NMR (400 MHz, CDCl3) δ: 1.02 (t, 3H, J =
8.3 Hz), 1.52 (m, 2H), 1.78 (brm, 3H), 1.98 (m, 1H), 2.1 (m,
1H), 2.41–2.71 (m, 3H), 3.03 (m, 2H), 3.35 (s, 3H), 3.58 (t,
1H, J = 11.2 Hz), 4.59–4.69 (m, 3H), 7.11–7.39 (m, 10H).
13C NMR (400 MHz, CDCl3) δ: 10.4, 25.3, 32.3, 33.9, 36.0,
46.8, 54.8, 55.8, 72.3, 75.2, 84.0, 98.2, 126.2, 128.2, 128.4,
128.7, 128.8, 129.0, 138.5, 142.4. MS calcd. for C24H33NO3:
383.5 (M+); found: 384.4.
1
[α]D +187.2 (c 1, CHCl3). IR (neat, cm–1): 3480. H NMR
(400 MHz, CDCl3) δ: 0.98 (t, 3H, J = 8.4 Hz), 1.45 (m, 1H),
1.83 (m, 1H), 1.99 (m, 1H), 2.18 (dd, 1H, J = 1.7, 15.4 Hz),
3.15 (dd, 1H, J = 1.7, 11.1 Hz), 3.37 (s, 3H), 3.82 (m, 1H),
4.22 (brs, 1H), 4.55 (d, 1H, J = 12.4 Hz), 4.76 (d, 1H, J =
12.4 Hz), 4.79 (d, 1H, J = 4.1 Hz), 7.23–7.38 (m, 5H). 13C
NMR (400 MHz, CDCl3) δ: 10.1, 24.9, 35.5, 55.3, 64.4,
67.3, 70.8, 78.4, 128.1, 128.3, 128.8, 138.4. MS calcd. for
C15H22NO4: 266.3 (M+); found: 284.2 (M + H2O+).
Methyl 4-O-benzyl-2,6-dideoxy-3-O-methanesulfonyl-6-
C-methyl-␣-D-ribo-hexopyranoside (10)
To a solution of compound 9 (0.33 g, 1.24 mmol) in
pyridine (6 mL) was added methanesulfonyl chloride
(0.24 mL, 3.1 mmol) at 0 °C and the solution was stirred for
12 h allowing it to warm to room temperature. The mixture
was diluted with Et2O (20 mL), washed sequentially with
cold dilute 5% HCl, aq. 5% NaHCO3 solution, water, and
brine, dried over Na2SO4, and concentrated under vacuum.
The residue was purified by column chromatography
(EtOAc–hexanes, 2:8) to obtain 10 (0.4 g, 94%). [α]D
+177.7 (c 1, CHCl3). IR (neat, cm–1): 1346. 1H NMR
(400 MHz, CDCl3) δ: 0.98 (t, 3H, J = 8.3 Hz), 1.21 (m, 1H),
1.93 (m, 2H), 2.37 (dd, 1H, J = 1.7, 15.4 Hz), 3.2 (s, 3H),
3.25 (m, 1H), 3.35 (m, 1H), 3.87 (t, 1H, J = 8.3 Hz), 4.51 (d,
1H, J = 12.4 Hz), 4.69 (m, 1H), 4.79 (d, 1H, J = 12.4 Hz),
5.24 (m, 1H), 7.29–7.42 (m, 5H). 13C NMR (400 MHz,
CDCl3) δ: 9.9, 24.7, 34.8, 39.6, 55.4, 67.5, 71.8, 74.1, 76.7,
96.9, 128.5, 128.7, 128.9, 137.6.
Methyl 4-O-benzyl-3-heptylamino-6-C-methyl-2,3,6-
trideoxy-␣-D-arabino-hexopyranoside (12b)
Following the same procedure as for compound 11 gave
12b in 62% yield. [α]D +26 (c 1.1, CHCl3). IR (neat, cm–1):
3820. 1H NMR (400 MHz, CDCl3) δ: 0.87 (m, 3H), 1.05 (m,
3H), 1.25 (brs, 6H), 1.39 (m, 2H), 1.51 (m, 2H), 1.63 (brs,
1H), 1.95 (m, 1H), 2.13 (m, 1H), 2.43 (m, 1H), 2.61 (m,
1H), 3.06 (m, 2H), 3.33 (s, 3H), 3.56 (t, 1H, J = 9.4 Hz),
4.61–4.75 (m, 3H), 7.29 (m, 5H). 13C NMR (400 MHz,
CDCl3) δ: 10.4, 14.5, 23.0, 25.3, 27.7, 29.6, 30.6, 32.2, 36.0,
47.4, 54.8, 55.8, 72.3, 75.1, 84.0, 98.2, 128.2, 128.3, 129.0,
138.7. MS calcd. for C22H37NO3: 363.5 (M+); found: 364.3.
Methyl 6-C-methyl-3-phenylethylamino-2,3,6-trideoxy-
␣-D-arabino-hexopyranoside (13a)
A mixture of compound 12a (35 mg, 0.0914 mmol) and
10% Pd (OH)2-on-carbon (3 mg) in EtOAc (2 mL) was
stirred under a hydrogen atmosphere for 14 h, the suspen-
sion was filtered, washed with MeOH (10 mL), concen-
trated, and purified by column chromatography (MeOH–
EtOAc, 1:99) to afford 13a (21 mg, 80%). [α]D +17 (c 0.5,
Methyl 3-azido-4-O-benzyl-6-C-methyl-2,3,6-trideoxy-␣-
D-arabino-hexopyranoside (11)
A mixture of compound 10 (395 mg, 1.15 mmol) and
NaN3 (395 mg, 5.3 mmol) in DMF (6 mL) was heated at
160 °C for 1.5 h under an argon atmosphere. The mixture
was filtered, washed with Et2O (20 mL), concentrated, and
the filtrate was purified by column chromatography (EtOAc–
hexanes, 3:97) to afford 11 (264 mg, 80%). [α]D +105.6 (c
1
CHCl3). IR (neat, cm–1): 3860, 3720. H NMR (400 MHz,
CDCl3) δ: 1.01 (t, 3H, J = 8.3 Hz), 1.42 (m, 2H), 1.94 (m,
3H), 2.09 (dd, 1H, J = 2 Hz), 2.56 (m, 1H), 2.69 (t, 2H, J =
6.9 Hz), 2.83 (m, 2H), 3.05 (t, 3H, J = 9.6 Hz), 3.32 (s, 3H),
3.42 (t, 1H, J = 11.2 Hz), 4.78 (brs, 1H), 7.19 (m, 3H), 7.29
(d, 2H, J = 7Hz). 13C NMR (400 MHz, CDCl3) δ: 10.2,
25.2, 32.1, 33.8, 35.5, 46.0, 54.8, 57.0, 73.5, 73.9, 98.5,
126.3, 128.8. MS calcd. for C17H27NO3: 293.2 (M+); found:
294.3.
1
1.1, CHCl3). IR (neat, cm–1): 2101. H NMR (400 MHz,
CDCl3) δ: 1.96 (t, 1H, J = 8.3 Hz), 1.51 (m, 1H), 1.61 (m,
1H), 1.96 (m, 1H), 2.19 (dd, 1H, J = 4.1, 13.5 Hz), 3.09 (t,
1H, J = 11 Hz), 3.34 (s, 3H), 3.54 (m, 1H), 3.91 (m, 1H),
4.63 (d, 1H, J = 12.8 Hz), 4.79 (m, 1H), 4.91 (d, 1H, J =
12.8 Hz), 7.28–7.44 (m, 5H). 13C NMR (400 MHz, CDCl3)
© 2005 NRC Canada

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Can. J. Chem. Vol. 83, 2005
Methyl 3-heptylamino-6-C-methyl-2,3,6-trideoxy-␣-D-
arabino-hexopyranoside (13b)
trans-Oxazolidinone lactol (15b)
Following the same procedure as for compound 14b gave
15b in 90% yield. [α]D +9.4 (c 0.65, CHCl3). IR (neat, cm–1):
1724. 1H NMR (400 MHz, CDCl3) δ: 0.88 (t, 3H, J =
6.9 Hz), 1.04 (t, 3H, J = 7.4 Hz), 1.27 (brs, 9H), 1.42–1.63
(m, 5H), 2.78–2.98 (m, 3H), 3.46 (m, 1H), 3.68 (m, 1H),
4.02 (t, 3H, J = 4.7 Hz), 4.27 (q, 1H, J = 4.7, 6.4 Hz), 9.89
(s, 1H). 13C NMR (400 MHz, CDCl3) δ: 10.1, 14.5, 23.0,
25.7, 27.0, 29.3, 32.1, 42.6, 47.6, 51.5, 73.8, 81.1, 157.5,
199.6. MS calcd. for C15H27NO4: 285.2 (M+); found: 286.2.
Following the same procedure compound as for 12b gave
13b as a light yellow solid (90%); mp 106 °C. [α]D +78.6 (c
1
0.5, CHCl3). IR (KBr, cm–1): 3307. H NMR (400 MHz,
CDCl3) δ: 0.87 (t, 3H, J = 5.8 Hz), 0.99 (t, 3H, J = 6.8 Hz),
1.26–1.48 (brm, 11H), 1.85 (m, 2H), 1.99 (m, 1H), 2.19 (m,
2H), 2.79 (q, 1H, 1H, J = 4.2, 8.9 Hz), 3.07 (q, 1H, J = 3.3,
8.9 Hz), 3.32 (s, 4H), 3.44 (t, 1H, J = 9.1 Hz), 3.59 (t, 1H,
J = 9.1 Hz), 4.79 (brs, 1H). 13C NMR (400 MHz, CDCl3) δ:
10.1, 14.3, 22.3, 24.4, 26.5, 27.5, 29.1, 31.1, 32.1, 46.3,
54.6, 58.4, 70.1, 72.2, 96.3. MS calcd. for C15H31NO3: 273.2
(M+); found: 274.2.
trans-Oxazolidinone lactone (16a)
To a mixture of compound 15a (10 mg, 0.0328 mmol) and
4 Å molecular sieves (15 mg) in DCM (2 mL) was added
pyridinium chlorochromate (11 mg, 0.0492 mmol) under an
argon atmosphere and the mixture was stirred for 4 h at
room temperature. After filtration and normal workup, the
mixture was purified by column chromatography (EtOAc–
hexanes, 4:6) to obtain compound 16a (7 mg, 68%). [α]D
+49.2 (c 0.2, CHCl3). IR (neat, cm–1): 1751. 1H NMR
(400 MHz, CDCl3) δ: 1.12 (t, 3H, J = 5.6 Hz), 1.59 (brs,
2H), 1.88 (m, 2H), 2.59 (m, 2H), 2.68–2.87 (m, 3H), 3.92
(m, 1H), 3.52 (m, 1H), 4.33 (m, 1H), 4.46 (m, 1H), 7.17–
7.32 (m, 5H). 13C NMR (400 MHz, CDCl3) δ: 7.3, 29.3,
30.1, 33.1, 33.2, 42.3, 46.6, 52.1, 80.5, 126.6, 128.7, 128.9,
141.2, 156.5, 207.2. MS calcd. for C17H21NO4: 303.2 (M+);
found: 304.6.
trans-Oxazolidinone glycoside (14a)
To a mixture of compound 13a (22 mg, 0.0751 mmol) and
Et3N (0.16 mL, 1.13 mmol) in DCM (4 mL) was added car-
bonyl diimidazole (60 mg, 0.376 mmol) under an argon at-
mosphere and the mixture was stirred for 5 h at room
temperature. The mixture was concentrated under vacuum
and purified by column chromatography (EtOAc–hexanes,
1:9) to obtain 14a (20 mg, 84%). [α]D +96.8 (c 0.5, CHCl3).
1
IR (neat, cm–1): 1764. H NMR (400 MHz, CDCl3) δ: 1.01
(t, 3H, J = 8.3 Hz), 1.59 (m, 1H), 1.75–2.15 (brm, 4H), 2.19
(m, 1H), 2.64 (t, 2H, J = 8.2 Hz), 2.83 (m, 2H), 3.19 (m,
1H), 3.33 (m, 1H), 3.39 (s, 3H), 3.59 (t, 1H, J = 10 Hz),
3.75 (t, 1H, J = 10 Hz), 3.79 (brm, 1H), 4.85 (brs, 1H), 7.19
(m, 3H), 7.26 (d, 2H, J = 8.3 Hz). 13C NMR (400 MHz,
CDCl3) δ: 9.4, 25.6, 29.9, 32.1, 33.6, 35.5, 43.8, 52.3, 57.4,
73.0, 80.5, 98.3, 126.5, 128.7, 128.9, 141.6, 159.7. MS
calcd. for C18H25NO4: 319.4 (M+); found: 320.6.
trans-Oxazolidinone lactone (16b)
Following the same procedure as for compound 15b gave
16b in 51% yield. [α]D +16.4 (c 0.25, CHCl3). IR (neat, cm–1):
1
1754, 1724. H NMR (400 MHz, CDCl3) δ: 0.86 (t, 3H, J =
6.9 Hz), 1.11 (t, 3H, J = 7.5 Hz), 1.29 (brs, 6H), 1.39–1.62
(m, 4H), 2.72 (m, 2H), 2.79–3.02 (m, 2H), 3.42 (m, 1H),
4.34 (q, 1H, J = 4.4, 6.9 Hz), 4.46 (m, 1H). 13C NMR
(400 MHz, CDCl3) δ: 7.3, 14.5, 23.0, 26.9, 27.6, 30.1, 33.1,
42.7, 46.8, 52.2, 73.4, 80.6, 156.5, 207.5. MS calcd. for
C15H25NO4: 283.2 (M+); found: 284.1.
trans-Oxazolidinone glycoside (14b)
Following the same procedure as for compound 13b gave
14b in 75% yield. [α]D +86.5 (c 1.35, CHCl3). IR (neat, cm–1):
1770. 1H NMR (400 MHz, CDCl3) δ: 0.87 (m, 3H), 1.04 (m,
3H), 1.24 (brs, 8H), 1.48–1.61 (m, 3H), 1.81 (m, 2H), 2.23
(m, 1H), 3.18 (m, 2H), 3.37 (s, 3H), 3.58 (m, 1H), 3.75 (m,
1H), 3.81 (m, 1H), 4.89 (brs, 1H). 13C NMR (400 MHz,
CDCl3) δ: 9.4, 14.5, 22.9, 25.6, 27.2, 28.2, 29.3, 32.1, 35.5,
44.0, 55.3, 57.2, 73.0, 80.5, 98.3, 159.7. MS calcd. for
C16H29NO4: 299.3 (M+); found: 300.2.
Methyl 4-O-benzyl-2,6-dideoxy-6-C-methyl-3-p-
nitrobenzoyl-␣-D-arabino-hexopyranoside (17)
To a mixture of compound 9 (1.5 g, 5.64 mmol),
triphenylphosphine (3.7 g, 14.1 mmol), and diisopropyl
azodicarboxylate (2.8 g, 14.1 mmol) in THF (30 mL) was
added p-nitrobenzoic acid (2.36 g, 14.1 mmol) in THF
(5 mL) under an argon atmosphere at 0 °C. The mixture was
stirred for 12 h at room temperature, then dilutedwith EtOAc
(50 mL), washed with aq. NaHCO3 and brine, dried over
Na2SO4, and concentrated under vacuum. The residue was
purified by column chromatography (EtOAc–hexanes, 5:95)
to afford 17 as white solid (1.83 g, 78%); mp 70 °C. [α]D
–0.9 (c 1, CHCl3). IR (KBr, cm–1): 1723. 1H NMR
(400 MHz, CDCl3) δ: 1.02 (t, 3H, J = 8.3 Hz), 1.56 (m, 1H),
1.82 (m, 1H), 1.99 (m, 1H), 2.38 (m, 1H), 3.38 (s, 3H), 3.43
(t, 1H, J = 9.6 Hz), 3.69 (t, 1H, J = 8.3 Hz), 4.65 (s, 2H),
4.81 (brs, 1H), 5.58 (m, 1H), 7.19 (s, 5H), 8.12 (d, 2H, J =
11 Hz), 8.25 (d, 2H, J = 11 Hz). 13C NMR (400 MHz,
CDCl3) δ: 10.3, 25.1, 35.8, 54.9, 72.1, 74.1, 75.3, 81.4,
123.9, 128.0, 128.2, 128.8, 131.1, 136.1, 138.2, 150.9,
164.1. MS calcd. for C22H25NO7: 415.2 (M+); found: 384.3
(M+ – OMe).
trans-Oxazolidinone lactol (15a)
To a solution of compound 14a (20 mg, 0.063 mmol) in
dioxane (2 mL) was added 6 N HCl (0.8 mL) and the mix-
ture was stirred at room temperature for 1 h. The mixture
was taken up in EtOAc (5 mL), neutralized with 10% aq.
NaHCO3 solution, and extracted with EtOAc (15 mL). The
organic phase was washed with brine, dried over Na2SO4,
concentrated, and the residue was purified by column chro-
matography (EtOAc–hexanes, 1:1) to afford 15a (18 mg,
94%). [α]D +13.6 (c 0.45, CHCl3). IR (neat, cm–1): 1718. H
1
NMR (400 MHz, CDCl3) δ: 1.03 (t, 3H, J = 8.7 Hz), 1.41–
1.71 (brm, 4H), 1.81–1.99 (m, 2H), 2.59–2.88 (m, 3H), 2.98
(m, 1H), 3.56 (m, 1H), 3.66 (m, 1H), 4.01 (t, 1H, J =
3.4 Hz), 4.25 (q, 1H, J = 9.8, 3.4 Hz), 7.19–7.29 (m, 5H),
9.89 (s, 1H). 13C NMR (400 MHz, CDCl3) δ: 10.0, 25.7,
29.2, 33.3, 42.3, 47.6, 51.5, 73.9, 81.1, 126.5, 128.7, 128.9,
141.5, 157.5, 199.2. MS calcd. for C17H23NO4: 305.3 (M+);
found: 306.0.
© 2005 NRC Canada

Hanessian and Kothakonda
807
2102. 1H NMR (300 MHz, CDCl3) δ: 0.99 (t, 3H, J =
7.4 Hz), 1.48 (m, 1H), 1.58 (s, 1H), 1.86–2.11 (m, 2H), 2.23
(m, 1H), 3.36 (s, 3H), 3.39 (m, 1H), 3.61 (m, 1H), 4.05 (m,
1H), 4.69 (d, 1H, J = 4.2 Hz). 13C NMR (300 MHz, CDCl3)
δ: 10.1, 24.1, 32.2, 55.6, 59.5, 69.4, 70.3, 96.3.
Methyl 4-O-benzyl-2,6-dideoxy-6-C-methyl-␣-D-arabino-
hexopyranoside (18)
To a solution of compound 17 (1.83 g, 4.41 mmol) in
MeOH (30 mL) was added catalytic NaOMe and the mixture
was stirred for 10 h at room temperature. The mixture was
concentrated under reduced pressure and purified by column
chromatography (EtOAc–hexanes, 1:5) to obtain 18 as white
solid (1.1 g, 93%); mp 76 °C. [α]D +68.6 (c 1, CHCl3). IR
Methyl 3-azido-4-p-methoxybenzyl-6-C-methyl-2,3,6-
trideoxy-␣-D-ribo-hexopyranoside (22)
1
(KBr, cm–1): 3225. H NMR (400 MHz, CDCl3) δ: 1.02 (t,
To a solution of compound 21 (190 mg, 0.946 mmol) in
DMF was added 60% NaH (62 mg, 1.61 mmol) at 0 °C and
the mixture was stirred for 10 min. p-Methoxybenzyl bro-
mide (5.6 mL, 0.27 mol/L in toluene) was added to the mix-
ture and the mixture stirred for 6 h allowing it to warm to
room temperature. The mixture was quenched with ice, ex-
tracted with Et2O (50 mL), washed with brine, dried over
Na2SO4, and concentrated under vacuum. The residue was
purified by column chromatography (EtOAc–hexanes, 1:9)
to afford 22 (285 mg, 94%). [α]D +174.8 (c 1.2, CHCl3). IR
3H, J = 7.6 Hz), 1.56 (m, 1H), 1.69 (m, 1H), 1.96 (m, 1H),
2.04–2.18 (m, 2H), 3.03 (t, 1H, J = 8.3 Hz), 3.33 (s, 3H),
3.49 (t, 1H, J = 8.4 Hz), 4.01 (m, 1H), 4.67–4.81 (m, 3H),
7.22–7.39 (m, 5H). 13C NMR (400 MHz, CDCl3) δ: 10.4,
25.1, 38.0, 54.8, 69.5, 72.0, 75.4, 85.0, 98.5, 128.2, 128.4,
129.1, 138.1. FAB+ MS calcd. for C15H22NO4: 266.2 (M+);
found: 265.1 (M+ – H).
Methyl 4-O-benzyl-2,6-dideoxy-3-O-methanesulfonyl-6-
C-methyl-␣-D-arabino-hexopyranoside (19)
1
(neat, cm–1): 2099. H NMR (400 MHz, CDCl3) δ: 0.97 (t,
3H, J = 7.4 Hz), 1.36 (m, 1H), 1.93 (m, 2H), 2.09 (dd, 1H,
J = 2.3, 4.9 Hz), 3.29 (dd, 1H, J = 3.5, 9.4 Hz), 3.36 (s, 3H),
3.81 (s, 3H), 3.87 (t, 1H, J = 7.1 Hz), 4.02 (m, 1H), 4.47 (d,
1H, J = 11.3 Hz), 4.62 (m, 2H), 6.89 (d, 2H, J = 8.4 Hz),
7.29 (d, 2H, J = 8.4 Hz). 13C NMR (400 MHz, CDCl3) δ:
10.1, 24.6, 33.6, 55.6, 68.1, 71.6, 78.2, 97.0, 114.3, 130.2.
To a solution of compound 18 (0.95 g, 3.57 mmol) in
pyridine (12 mL) was added methanesulfonyl chloride
(0.69 mL, 8.93 mmol) at 0 °C and the mixture was stirred
for 12 h allowing it to warm to room temperature. The mix-
ture was diluted with Et2O (20 mL), washed sequentially
with cold dilute 5% HCl, aq. 5% NaHCO3 solution, and wa-
ter then with brine, dried over Na2SO4, and concentrated un-
der vacuum. The residue was purified by column
chromatography (EtOAc–hexanes, 1:4) to obtain 19 as white
solid (1.2 g, 97%); mp 75 °C. [α]D +98 (c 1, CHCl3). IR
Methyl 4-p-methoxybenzyl-6-C-methyl-3-
phenylethylamino-2,3,6-trideoxy-␣-D-ribo-
hexopyranoside (23a)
1
(KBr, cm–1): 1356. H NMR (400 MHz, CDCl3) δ: 1.02 (t,
To a solution of compound 22 (46 mg, 0.144 mmol) in
THF was added trimethylphosphine (0.55 mL, 1 mol/L in to-
luene) and the mixture was stirred under an argon atmo-
sphere for 30 min. Water (25 µL) was added to the mixture
and it was stirred under reflux conditions for 45 min. The
mixture was concentrated under vacuum and dried properly.
The residue was diluted with dry MeOH (3 mL) under an ar-
gon atmosphere, the requisite aldehyde (0.14 mmol) was
added, followed by the addition of AcOH (32 µL), then the
mixture was stirred for 1 h. NaCNBH3 (18 mg, 0.287 mmol)
was added and the mixture stirred for 12 h at room tempera-
ture. The mixture was concentrated under vacuum, diluted
with EtOAc (10 mL), washed with 10% NaHCO3 and brine,
the organic phase was dried over Na2SO4, concentrated un-
der vacuum, and the residue was purified by column chro-
matography (EtOAc–hexanes, 1:1) to afford 23a (79%). [α]D
+134 (c 1, CHCl3). IR (neat, cm–1): 3309. 1H NMR
(400 MHz, CDCl3) δ: 0.97 (t, 3H, J = 7.4 Hz), 1.35 (m, 2H),
1.84 (m, 2H), 2.04 (m, 3H), 2.64 (m, 2H), 2.81 (m, 1H),
2.91 (m, 1H), 3.20 (m, 1H), 3.32 (m, 1H), 3.37 (s, 3H), 3.68
(m, 1H), 3.79 (m, 3H), 4.52 (m, 2H), 4.69 (m, 1H), 6.88 (d,
2H, J = 8.1 Hz), 7.19 (t, 3H, J = 7.6 Hz), 7.35 (d, 4H, J =
8.1 Hz). 13C NMR (400 MHz, CDCl3) δ: 9.9, 24.9, 29.8,
30.8, 33.4, 47.3, 53.6, 55.7, 68.9, 72.1, 97.8, 114.3, 126.6,
128.8, 128.9, 130.5, 141.3, 159.9. MS calcd. for C25H35NO4:
413.3 (M+); found: 414.4.
3H, J = 8.2 Hz), 1.49 (m, 1H), 1.96 (m, 2H), 2.42 (m, 1H),
2.89 (s, 3H), 3.22–3.33 (m, 4H), 3.57 (t, 1H, J = 8.3 Hz),
4.67 (m, 1H), 4.78 (m, 2H), 4.91 (m, 1H), 7.22–7.39 (m,
5H). 13C NMR (400 MHz, CDCl3) δ: 10.3, 25.0, 37.5, 38.2,
54.9, 72.3, 75.6, 81.0, 97.8, 128.2, 128.4, 129.0, 138.0. MS
calcd. for C16H24O6S: 344.1 (M+); found: 362.3 (M+ + H2O).
Methyl 2,6-dideoxy-3-O-methanesulfonyl-6-C-methyl-␣-
D-arabino-hexopyranoside (20)
A mixture of compound 19 (1.0 g, 2.91 mmol) and 10%
Pd-on-carbon (10 mg) in EtOAc (10 mL) was stirred under a
hydrogen atmosphere for 10 h; the mixture was filtered,
washed with EtOAc (10 mL), concentrated, and purified by
column chromatography (EtOAc–hexanes, 3:7) to afford 20
as a solid (0.69 g, 93%); mp 88 °C. [α]D +65.2 (c 0.5,
1
CHCl3). IR (KBr, cm–1): 3540. H NMR (400 MHz, CDCl3)
δ: 1.01 (t, 3H, J = 6.9 Hz), 1.49 (m, 1H), 1.95 (m, 2H), 2.34
(dd, 1H, J = 4.8, 12.4 Hz), 3.11 (s, 3H), 3.32 (s, 3H), 3.41 (t,
1H, J = 8.9 Hz), 3.49 (t, 1H, J = 9.4 Hz), 4.80 (s, 1H), 4.91
(m, 1H). 13C NMR (300 MHz, CDCl3) δ: 10.1, 23.9, 36.5,
38.1, 54.8, 72.2, 73.3, 80.9, 97.5.
Methyl 3-azido-6-C-methyl-2,3,6-trideoxy-␣-D-ribo-
hexopyranoside (21)
A mixture of compound 20 (0.65 g, 2.56 mmol) and NaN3
(0.97 g, 14.84 mmol) in DMF (12 mL) was heated at 125 °C
for 12 h under an argon atmosphere. The mixture was fil-
tered, washed with Et2O (40 mL), the filtrate concentrated
and purified by column chromatography (EtOAc–hexanes,
1:9) to afford 21 as a crystalline white solid (0.39 g, 76%);
mp 75 °C. [α]D +277.8 (c 0.5, CHCl3). IR (KBr, cm–1):
Methyl 3-heptylamino-4-p-methoxybenzyl-6-C-methyl-
2,3,6-trideoxy-␣-D-ribo-hexopyranoside (23b)
Following the same procedure as for compound 22 gave
23b in 65% yield. [α]D +118 (c 1, CHCl3). IR (neat, cm–1):
3219. 1H NMR (400 MHz, CDCl3) δ: 0.91 (t, 3H, J =
© 2005 NRC Canada

808
Can. J. Chem. Vol. 83, 2005
7.4 Hz), 0.98 (t, 3H, J = 7.4 Hz), 1.31 (brm, 10H), 1.63 (m,
2H), 1.85 (m, 2H), 2.13 (m, 1H), 2.94 (m, 2H), 3.24–3.42
(m, 5H), 3.69 (t, 1H, J = 7.3 Hz), 3.82 (s, 3H), 4.59 (m, 2H),
4.74 (brs, 1H), 6.88 (d, 2H, J = 8.3 Hz), 7.33 (d, 2H, J =
8.3 Hz). 13C NMR (400 MHz, CDCl3) δ: 9.3, 13.9, 22.4,
24.3, 26.5, 28.7, 29.6, 31.5, 46.9, 53.2, 55.2, 68.1, 71.6,
97.0, 113.9, 128.9, 130.1, 159.5. MS calcd. for C23H39NO4:
393.3 (M+); found: 394.4.
rium(IV) nitrate (151 mg, 0.277 mmol) and the mixture was
vigorously stirred for 12 h at room temperature. The mixture
was diluted with EtOAc (10 mL), washed with aq. 5%
NaHCO3 and then with brine, dried over Na2SO4, and con-
centrated under vacuum. The residue was purified by col-
umn chromatography (MeOH–EtOAc, 1:99) to afford 24a
(19 mg, 89%). [α]D +123.1 (c 0.8, CHCl3). IR (neat, cm–1):
1
3342, 3233. H NMR (400 MHz, CDCl3) δ: 1.02 (t, 3H, J =
9.5 Hz), 1.42 (m, 1H), 1.77 (m, 1H), 1.84 (m, 2H), 1.98 (m,
1H), 2.14 (dd, 1H, J = 2.1, 13.4 Hz), 2.48 (m, 1H), 2.66 (m,
2H), 2.85 (m, 2H), 3.24 (m, 1H), 3.38 (m, 4H), 4.74 (m,
1H), 7.18–7.34 (m, 5H). 13C NMR (400 MHz, CDCl3) δ:
10.3, 25.2, 31.6, 31.7, 33.7, 47.5, 55.3, 55.4, 68.7, 70.3,
98.5, 126.3, 128.8, 142.2. MS calcd. for C17H27NO3: 293.2
(M+); found: 294.2.
Methyl 3-(4-quinolinyl)propylamino-4-p-methoxybenzyl-
6-C-methyl-2,3,6-trideoxy-α-D-ribo-hexopyranoside (23c)
Following the same procedure as for compound 22 gave
23c in 76% yield. [α]D +78.7 (c 1.9, CHCl3). IR (neat, cm–1):
3350. 1H NMR (400 MHz, CDCl3) δ: 0.98 (t, 3H, J =
7.4 Hz), 1.25 (m, 1H), 1.41 (m, 1H), 1.84 (m, 1H), 2.01 (m,
3H), 2.72 (m, 1H), 2.84 (m, 1H), 3.03 (m, 1H), 3.13 (m,
2H), 3.25 (dd, 1H, J = 3.8, 8.4 Hz), 3.38 (s, 3H), 3.75–3.83
(m, 4H), 4.52 (m, 2H), 4.67 (m, 1H), 6.83 (m, 2H), 7.22 (m,
3H), 7.56 (t, 1H, J = 8.1 Hz), 7.67 (t, 1H, J = 8.1 Hz), 8.05
(d, 1H, J = 8.3 Hz), 8.11 (d, 1H, J = 8.3 Hz), 8.79 (d, 1H,
J = 4.4 Hz). 13C NMR (400 MHz, CDCl3) δ: 10.2, 24.9,
30.0, 30.4, 32.5, 47.8, 52.6, 55.6, 55.7, 69.5, 71.2, 98.4,
114.3, 121.1, 124.0, 126.8, 127.9, 129.5, 130.0, 130.5,
148.4, 148.7, 150.7, 159.7. MS calcd. for C28H36N2O4: 464.3
(M+); found: 465.5.
Methyl 3-heptylamino-6-C-methyl-2,3,6-trideoxy-␣-D-
ribo-hexopyranoside (24b)
Following the same procedure as for compound 23b gave
24b in 75% yield. [α]D +74.1 (c 1.5, CHCl3). IR (neat, cm–1):
3339. 1H NMR (400 MHz, CDCl3) δ: 0.89 (t, 3H, J =
7.2 Hz), 0.99 (t, 3H, J = 7.1 Hz), 1.31 (brm, 8H), 1.44 (m,
3H), 1.74 (m, 1H), 1.97 (m, 1H), 2.14 (dd, 1H, J = 1.5,
13.2 Hz), 2.38 (m, 1H), 2.71–2.84 (m, 2H), 3.18 (m, 1H),
3.21–3.37 (m, 4H), 4.72 (brs, 1H). 13C NMR (400 MHz,
CDCl3) δ: 10.4, 14.5, 23.1, 25.2, 27.5, 29.6, 30.1, 31.7, 32.3,
48.5, 55.0, 55.2, 68.7, 70.4, 98.6. MS calcd. for C15H31NO3:
273.2 (M+); found: 274.2.
Methyl 3-(3-quinolinyl)-E-propenylamino-4-p-
methoxybenzyl-6-C-methyl-2,3,6-trideoxy-␣-D-ribo-
hexopyranoside (23d)
Following the same procedure as for compound 22 gave
23d in 70% yield. [α]D +49.9 (c 1.1, CHCl3). IR (neat, cm–1):
3413. 1H NMR (400 MHz, CDCl3) δ: 0.99 (t, 3H, J =
9.4 Hz), 1.37 (m, 1H), 1.86 (m, 2H), 2.06 (m, 1H), 3.29 (m,
1H), 3.41 (s, 3H), 2.91 (m, 1H), 3.20 (m, 1H), 3.32 (m, 1H),
3.37 (s, 3H), 3.59–3.91 (m, 6H), 4.51–4.85 (m, 4H), 6.84
(m, 3H), 7.29 (m, 3H), 7.53 (m, 1H), 7.67 (t, 1H, J =
9.7 Hz), 7.78 (m, 1H), 8.02 (m, 2H), 8.88 (s, 1H). MS calcd.
for C28H34N2O4: 462.3 (M+); found: 342.1 (M+ – PMB).
Methyl 3-(4-quinolinyl)propylamino-6-C-methyl-2,3,6-
trideoxy-␣-D-ribo-hexopyranoside (24c)
Following the same procedure as for compound 23c gave
24c in 83% yield. [α]D +36.9 (c 1.6, CHCl3). IR (neat, cm–1):
3340. 1H NMR (400 MHz, CDCl3) δ: 1.01 (t, 3H, J =
7.4 Hz), 1.29 (m, 1H), 1.42 (m, 1H), 1.78 (m, 1H), 1.97 (m,
2H), 2.17 (m, 1H), 2.57 (m, 1H), 2.79 (brs, 1H), 2.98 (m,
2H), 3.17 (t, 1H, J = 7.8 Hz), 3.22–3.35 (m, 4H), 4.75 (brs,
1H), 7.24 (d, 3.2H), 7.58 (t, 1H, J = 7.3 Hz), 7.70 (t, 1H, J =
7.3 Hz), 8.05 (d, 1H, J = 8.4 Hz), 8.12 (d, 1H, J = 8.4 Hz),
8.82 (d, 1H, J = 4.3 Hz). 13C NMR (400 MHz, CDCl3) δ:
10.3, 25.2, 30.0, 30.1, 31.0, 31.9, 48.1, 55.2, 68.7, 70.4,
98.7, 121.2, 123.9, 126.8, 127.9, 129.5, 130.0, 130.6, 148.4,
148.7, 150.5. MS calcd. for C20H28N2O3: 344.4 (M+); found:
345.3.
Methyl 3-[4-(3-pyridinyl)-1-imidazolyl)butylamino-4-p-
methoxybenzyl-6-C-methyl-2,3,6-trideoxy-␣-D-ribo-
hexopyranoside (23e)
Following the same procedure as for compound 22 gave
23e in 80% yield. [α]D +71.5 (c 0.2, MeOH). IR (neat, cm–1):
1
3360. H NMR (400 MHz, CD3OD) δ: 0.98 (t, 3H, J =
7.8 Hz), 1.46 (m, 1H), 1.58 (m, 2H), 1.73–1.86 (m, 3H),
2.01 (m, 1H), 2.67 (m, 1H), 2.81 (m, 1H), 3.33 (m, 5H),
3.77 (s, 3H), 3.79 (m, 1H), 4.10 (t, 1H, J = 7.1 Hz), 4.54 (m,
2H), 4.69 (brs, 1H), 6.87 (d, 2H, J = 8.1 Hz), 7.27 (d, 2H,
J = 8.1 Hz), 7.43 (m, 1H), 7.68 (s, 1H), 7.79 (s, 1H), 8.15
(q, 1H, J = 2.1, 8.6 Hz), 8.39 (m, 1H), 8.91 (s, 1H). 13C
NMR (400 MHz, CD3OD) δ: 9.1, 15.7, 16.4, 24.3, 28.2,
46.7, 47.0, 52.6, 54.5, 54.7, 69.7, 71.1, 76.0, 97.8, 113.8,
117.1, 124.4, 130.0, 130.9, 133.0, 138.2, 138.8, 145.6,
147.0, 160.0. MS calcd. for C28H38N4O4: 494.3 (M+); found:
495.4.
Methyl 3-(3-quinolinyl)-E-propenylamino-6-C-methyl-
2,3,6-trideoxy-␣-D-ribo-hexopyranoside (24d)
Following the same procedure as for compound 23d gave
24d in 72% yield. [α]D +89.8 (c 0.5, CHCl3). IR (neat, cm–1):
3351. 1H NMR (400 MHz, CDCl3) δ: 0.99 (t, 3H, J =
7.2 Hz), 1.24 (m, 1H), 1.47 (m, 1H), 1.83 (d, 1H, J =
14.3 Hz), 1.99 (m, 1H), 2.21 (d, 1H, J = 14.3 Hz), 3.18 (m,
1H), 3.37 (s, 3H), 3.42 (m, 1H), 3.59 (m, 1H), 3.83 (m, 1H),
4.82 (brs, 1H), 6.59 (m, 1H), 6.79 (d, 1H, J = 15.2 Hz), 7.51
(t, 1H, J = 8.2 Hz), 7.69 (t, 1H, J = 8.2 Hz), 7.79 (d, 1H, J =
7.6 Hz), 8.05 (m, 2H), 8.99 (s, 1H). MS calcd. for
C20H26N2O3: 342.2 (M+); found: 343.2.
Methyl 6-C-methyl-3-phenylethylamino-2,3,6-trideoxy-
␣-D-ribo-hexopyranoside (24a)
To a solution of compound 23a (30 mg, 0.073 mmol) in
AcCN and water (2 mL, 9:1) was added ammonium ce-
Methyl 3-[4-(3-pyridinyl)-1-imidazolyl)butylamino-6-C-
methyl-2,3,6-trideoxy-␣-D-ribo-hexopyranoside (24e)
Following the same procedure as for compound 23e gave
© 2005 NRC Canada

Hanessian and Kothakonda
809
24e in 90% yield. [α]D +19.5 (c 1.5, MeOH). IR (neat, cm–1):
8.7 Hz), 4.39 (dd, 1H, J = 1.9, 13.2 Hz), 4.78 (brs, 1H), 6.42
(m, 1H), 6.79 (d, 1H, J = 15.2 Hz), 7.59 (t, 1H, J = 8.2 Hz),
7.79 (t, 1H, J = 8.2 Hz), 7.85 (d, 1H, J = 7.6 Hz), 8.18 (m,
2H), 8.99 (s, 1H). 13C NMR (400 MHz, CDCl3) δ: 10.2,
26.6, 29.9, 30.1, 44.9, 46.2, 51.5, 55.5, 69.1, 74.6, 77.7,
97.2, 127.5, 128.2, 128.4, 129.7, 130.8, 134.7, 146.5, 148.0,
157.9. MS calcd. for C21H24N2O4: 368.2 (M+); found: 369.2.
1
3200. H NMR (400 MHz, CD3OD) δ: 1.01 (t, 3H, J =
7.2 Hz), 1.42 (m, 1H), 1.64–2.01 (brm, 6H), 2.22 (dd, 1H,
J = 2.1, 8.2 Hz), 3.12 (m, 1H), 3.11 (m, 1H), 3.29 (s, 3H),
3.52 (m, 1H), 3.62 (m, 2H), 4.19 (m, 2H), 4.79 (brs, 1H),
7.48 (m, 1H), 7.79 (s, 1H), 7.99 (s, 1H), 8.21 (m, 1H), 8.41
(m, 1H), 8.94 (s, 1H). 13C NMR (400 MHz, CD3OD) δ: 9.0,
22.9, 24.6, 28.7, 46.0, 47.0, 54.3, 56.5, 66.9, 69.8, 97.0,
117.9, 124.9, 134.0, 138.7, 144.9, 146.7. MS calcd. for
C20H30N2O3: 374.2 (M+); found: 375.3.
cis-Oxazolidinone glycoside (25e)
Following the same procedure as for compound 24e gave
25e in 75% yield. [α]D +31.3 (c 1, MeOH). IR (neat, cm–1):
cis-Oxazolidinone glycoside (25a)
1745. 1H NMR (400 MHz, CDCl3) : 1.01 (t, 3H, J =
δ
To a mixture of compound 24a (16 mg, 0.0546 mmol) and
Et3N (0.12 mL, 0.82 mmol) in DCM (3 mL) was added
carbonyldiimidazole (45 mg, 0.273 mmol) under an argon
atmosphere and the mixture was stirred for 5 h at room tem-
perature. The mixture was concentrated under vacuum and
purified by column chromatography (EtOAc–hexanes, 1:4)
to obtain 25a (20 mg, 91%). [α]D +128.6 (c 1, CHCl3). IR
7.5 Hz), 1.59 (m, 3H), 1.81 (m, 2H), 1.89 (m, 2H), 2.19 (m,
1H), 3.14 (m, 2H), 3.39 (s, 3H), 3.64 (m, 1H), 3.78 (m, 1H),
4.05 (t, 2H, J = 6.9 Hz), 4.17 (t, 1H, J = 8.6 Hz), 4.71 (t,
1H, J = 5.9 Hz), 7.31 (m, 1H), 7.55 (s, 1H), 7.92 (m, 1H),
8.09 (dd, 1H, J = 1.7, 7.9 Hz), 8.47 (m, 1H), 8.98 (s, 1H).
13C NMR (400 MHz, CD3OD) δ: 9.1, 24.4, 26.2, 28.0, 29.2,
41.3, 46.8, 51.5, 54.3, 69.0, 74.8, 97.4, 117.2, 120.9, 124.4,
131.0, 133.0, 135.1, 138.2, 138.9, 145.6, 147.0, 159.2. MS
calcd. for C21H28N4O4: 400.2 (M+); found: 401.3.
1
(neat, cm–1): 1752. H NMR (400 MHz, CDCl3) δ: 1.02 (t,
3H, J = 8.3 Hz), 1.54 (m, 1H), 1.72 (m, 1H), 1.83 (m, 4H),
2.14 (m, 1H), 2.63 (t, 1H, J = 8.4 Hz), 3.06 (m, 1H), 3.38 (s,
3H), 3.56 (m, 1H), 3.65 (m, 1H), 4.11 (t, 1H, J = 8.3 Hz),
4.72 (t, 1H, J = 6.9 Hz), 7.12–7.34 (m, 5H). 13C NMR
(400 MHz, CDCl3) δ: 10.2, 26.7, 29.5, 30.0, 33.5, 51.3,
55.4, 69.4, 74.5, 97.3, 126.5, 128.7, 128.9, 141.6, 158.0. MS
calcd. for C18H25NO4: 319.2 (M+); found: 320.2.
cis-Oxazolidinone lactol (26a)
To a solution of compound 25a (14 mg, 0.0438 mmol) in
dioxane (2 mL) was added 6 N HCl (0.7 mL) and the mix-
ture was stirred at room temperature for 1 h. The mixture
was taken up in EtOAc (5 mL), neutralized with 10%
NaHCO3, extracted with EtOAc (15 mL), and the organic
phase was washed with brine, dried over Na2SO4, concen-
trated and the residue was purified by column chromatogra-
phy (EtOAc–hexanes, 1:1) to afford 26a (11 mg, 84%). [α]D
+68.7 (c 0.75, CHCl3). IR (neat, cm–1): 3398, 1733. 1H
NMR (300 MHz, CDCl3) δ: 0.99 (t, 3H, J = 9.6 Hz), 1.51
(m, 1H), 1.58–1.98 (m, 4H), 2.01–2.33 (m, 1H), 2.64 (t, 2H,
J = 9.4 Hz), 3.08 (m, 1H), 3.38–3.78 (m, 2H), 3.79–4.27 (m,
2H), 5.05–5.29 (m, 1H), 7.14–7.35 (m, 5H). 13C NMR
(300 MHz, CDCl3) δ: 9.8, 9.9, 26.5, 26.6, 29.3, 29.5, 30.1,
30.8, 31.5, 33.5, 42.3, 42.4, 51.3, 52.6, 69.9, 72.9, 74.5,
75.2, 90.9, 92.3, 126.5, 126.6, 128.7, 128.9, 130.0, 141.4,
141.5, 157.9, 158.4. MS calcd. for C17H23NO4: 302.2 (M+);
found: 306.2.
cis-Oxazolidinone glycoside (25b)
Following the same procedure as for compound 24b gave
25b in 90% yield. [α]D +127.8 (c 0.6, CHCl3). IR (neat, cm–1):
1751. 1H NMR (400 MHz, CDCl3) δ: 0.83 (t, 3H, J =
6.7 Hz), 1.05 (t, 3H, J = 6.7 Hz), 1.30 (brm, 8H), 1.57 (m,
3H), 1.81 (m, 2H), 2.24 (m, 1H), 2.98 (m, 1H), 3.39 (s, 3H),
3.47 (m, 1H), 3.67 (m, 1H), 3.82 (q, 1H, J = 7.2, 14.5 Hz),
4.18 (t, 1H, J = 8.2 Hz), 4.74 (t, 1H, J = 6.6 Hz). 13C NMR
(400 MHz, CDCl3) δ: 10.2, 14.5, 23.0, 26.7, 27.1, 27.9,
29.3, 30.0, 32.1, 42.4, 51.2, 55.4, 69.5, 74.5, 97.4, 158.0.
MS calcd. for C16H29NO4: 299.2 (M+); found: 300.2.
cis-Oxazolidinone glycoside (25c)
Following the same procedure as for compound 24c gave
25c in 68% yield. [α]D +108.2 (c 1.2, CHCl3). IR (neat, cm–1):
1751. 1H NMR (400 MHz, CDCl3) δ: 1.02 (t, 3H, J =
7.4 Hz), 1.27 (m, 1H), 1.57 (m, 1H), 1.81 (m, 2H), 2.04 (m,
1H), 2.18 (m, 1H), 3.12 (t, 2H, J = 6.9 Hz), 3.21 (m, 1H),
3.36 (s, 3H), 3.58 (m, 1H), 3.68 (m, 1H), 3.81 (m, 1H), 4.15
(t, 1H, J = 8.3 Hz), 4.71 (t, 1H, J = 5.6 Hz), 7.27 (d, 1H, J =
3.2 Hz), 7.59 (t, 1H, J = 8.1 Hz), 7.73 (t, 1H, J = 8.1 Hz),
8.01 (d, 1H, J = 8.5 Hz), 8.13 (d, 1H, J = 8.5 Hz), 8.82 (d,
1H, J = 4.3 Hz). 13C NMR (400 MHz, CDCl3) δ: 10.2, 26.6,
28.1, 29.6, 30.0, 42.4, 51.5, 69.2, 74.5, 97.1, 121.1, 123.7,
127.1, 127.8, 129.7, 130.0, 130.8, 147.5, 148.7, 150.6,
158.2. MS calcd. for C27H26N2O4: 370.2 (M+); found: 371.2.
cis-Oxazolidinone lactol (26b)
Following the same procedure as for compound 25b gave
26b in 73% yield. [α]D +80.8 (c 0.65, CHCl3). IR (neat, cm–1):
1739. 1H NMR (400 MHz, CDCl3) δ: 0.84 (t, 3H, J =
7.2 Hz), 0.99 (t, 3H, J = 7.3 Hz), 1.28 (m, 8H), 1.51 (m,
3H), 1.61–1.97 (m, 3H), 2.06–2.37 (m, 1H), 2.91–3.53 (m,
3H), 3.81 (m, 1H), 4.21 (t, 1H, J = 11.1 Hz), 5.09–5.29 (m,
1H). 13C NMR (400 MHz, CDCl3) δ: 9.8, 9.9, 14.5, 23.0,
26.5, 26.6, 27.0, 27.6, 27.9, 29.3, 30.9, 31.5, 32.1, 42.5,
51.2, 52.5, 69.9, 72.8, 74.5, 75.3, 91.0, 92.4, 158.0, 158.4.
MS calcd. for C15H27NO4: 285.2 (M+); found: 286.2.
cis-Oxazolidinone lactol (26c)
cis-Oxazolidinone glycoside (25d)
Following the same procedure as for compound 25c gave
Following the same procedure as for compound 24d gave
25d in 65% yield. [α]D +39.8 (c 0.45, CHCl3). IR (neat, cm–1):
1747. 1H NMR (400 MHz, CDCl3) δ: 1.03 (t, 3H, J =
7.4 Hz), 1.59 (m, 1H), 1.84 (m, 2H), 2.28 (m, 1H), 3.42 (s,
3H), 3.78 (t, 1H, J = 8.9 Hz), 3.95 (m, 2H), 4.25 (t, 1H, J =
26c in 89% yield. [α]D +62.8 (c 0.6, CHCl3). IR (neat, cm–1):
1
3368, 1748. H NMR (300 MHz, CDCl3) δ: 0.99 (t, 3H, J =
7.4 Hz), 1.24 (m, 1H), 1.57 (m, 1H), 1.72–2.28 (brm, 4H),
3.12 (m, 2H), 3.21–3.38 (m, 1H), 3.42–3.64 (m, 2H), 3.77–
3.91 (m, 1H), 4.13 (m, 1H), 5.05–5.29 (m, 1H), 7.25 (m,
© 2005 NRC Canada

810
Can. J. Chem. Vol. 83, 2005
1H), 7.58 (m, 1H), 7.69 (t, 1H, J = 7.3 Hz), 8.01 (t, 1H, J =
7.3 Hz), 8.13 (d, 1H, J = 8.4 Hz), 8.77 (dd, 1H, J = 4.3,
15.4 Hz). 13C NMR (400 MHz, CDCl3) δ: 9.9, 10.0, 26.5,
26.6, 28.2, 28.3, 29.7, 29.7, 30.9, 31.8, 42.5, 42.6, 51.7,
53.3, 69.6, 73.1, 74.5, 75.3, 90.7, 92.1, 120.9, 121.1, 123.6,
123.7, 127.1, 127.8, 129.7, 129.8, 130.4, 130.5, 147.6,
147.7, 148.4, 148.5, 150.4, 150.5, 158.2, 158.7. MS calcd.
for C20H24N2O4: 356.2 (M+); found: 357.2.
1H), 3.51 (m, 1H), 4.21 (m, 2H), 4.23 (t, 1H, J = 9.5 Hz).
13C NMR (400 MHz, CDCl3) δ: 9.5, 14.5, 22.9, 25.6, 27.0,
27.6, 29.3, 32.1, 34.1, 42.8, 51.3, 71.9, 79.5, 156.5, 169.0.
MS calcd. for C15H25NO4: 283.2 (M+); found: 284.2.
cis-Oxazolidinone lactone (27c)
Following the same procedure as for compound 26c gave
27c in 76% yield as crystalline solid; mp 102 °C. [α]D +78.9
1
(c 0.45, CHCl3). IR (KBr, cm–1): 1750. H NMR (400 MHz,
cis-Oxazolidinone lactol (26d)
CDCl3) δ: 1.09 (t, 3H, J = 7.4 Hz), 1.77 (m, 1H), 1.91–2.15
(m, 3H), 2.57 (m, 1H), 2.92 (dd, 1H, J = 5.6, 14.2 Hz), 3.13
(t, 3H, J = 7.8 Hz), 3.21 (m, 1H), 3.62 (m, 1H), 4.06 (m,
1H), 4.18 (m, 1H), 4.38 (t, 3H, J = 8.9 Hz), 7.26 (d, 1H, J =
3.9 Hz), 7.59 (t, 1H, J = 7.8 Hz), 7.72 (t, 1H, J = 7.8 Hz),
7.98 (d, 1H, J = 8.3 Hz), 8.14 (d, 1H, J = 8.3 Hz), 8.83 (d,
1H, J = 4.3 Hz). 13C NMR (400 MHz, CDCl3) δ: 9.6, 22.1,
25.6, 27.8, 29.7, 34.1, 42.7, 51.4, 71.9, 89.6, 121.1, 123.5,
127.2, 129.8, 130.8, 146.9, 148.7, 150.6, 156.5, 168.7. MS
calcd. for C20H22N2O4: 354.2 (M+); found: 355.2.
Following the same procedure as for compound 25d gave
26d in 97% yield. [α]D +29.8 (c 0.8, CHCl3). IR (neat, cm–1):
1
3364, 1750. H NMR (400 MHz, CDCl3) δ: 1.01 (t, 3H, J =
7.2 Hz), 1.61 (m, 1H), 1.79–2.08 (brm, 2H), 2.21–2.41 (m,
1H), 3.72 (m, 1H), 3.98 (m, 2H), 4.32 (m, 2H), 5.18–5.35
(m, 1H), 6.44 (m, 1H), 6.79 (d, 1H, J = 15.2 Hz), 7.59 (t,
1H, J = 8.2 Hz), 7.72 (t, 1H, J = 8.2 Hz), 7.82 (d, 1H, J =
7.6 Hz), 8.18 (m, 2H), 9.01 (s, 1H). 13C NMR (400 MHz,
CDCl3) δ: 9.8, 9.9, 26.6, 30.1, 30.9, 31.7, 45.0, 45.1, 51.6,
53.1, 67.5, 69.5, 73.1, 74.6, 75.3, 77.6, 90.7, 92.2, 126.1,
126.9, 127.8, 129.1, 129.6, 130.4, 130.5, 133.9, 148.9,
158.9. MS calcd. for C20H22N2O4: 354.2 (M+); found: 355.2.
cis-Oxazolidinone lactone (27d)
Following the same procedure as for compound 26d gave
27d in 69% yield. [α]D +64.3 (c 0.4 CHCl3). IR (neat, cm–1):
1749. 1H NMR (400 MHz, CDCl3) δ: 1.12 (t, 3H, J =
9.4 Hz), 1.81 (m, 1H), 2.02 (m, 1H), 2.74 (m, 1H), 3.05 (dd,
1H, J = 4.3, 14.5 Hz), 3.89 (m, 1H), 4.28 (m, 2H), 4.38 (dd,
1H, J = 4.9, 14.9 Hz), 4.53 (t, 1H, J = 8.9 Hz), 6.42 (m, 1H),
6.82 (d, 1H, J = 15.2 Hz), 7.64 (t, 1H, J = 8.2 Hz), 7.79 (t,
1H, J = 8.2 Hz), 7.88 (d, 1H, J = 7.6 Hz), 8.21 (m, 2H), 9.04
(s, 1H). 13C NMR (400 MHz, CDCl3) δ: 9.6, 25.6, 34.1,
45.4, 51.3, 72.1, 77.7, 79.5, 125.1, 217.9, 128.4, 129.4,
130.4, 132.0, 133.9, 156.4, 168.8. MS calcd. for C20H20N2O4:
352.1 (M+); found: 353.2.
cis-Oxazolidinone lactol (26e)
Following the same procedure as for compound 25e gave
26e in 74% yield. [α]D +27.6 (c 0.45, MeOH). IR (neat, cm–1):
3120, 1745. 1H NMR (300 MHz, CD3OD) δ: 0.99 (t, 3H, J =
7.3 Hz), 1.63 (m, 5H), 1.89 (m, 2H), 2.12–2.31 (m, 1H),
3.14 (m, 1H), 3.41 (m, 2H), 3.73–3.96 (m, 1H), 4.14 (m,
2H), 4.25 (m, 1H), 4.91–5.19 (m, 1H), 7.45 (m, 1H), 7.71 (s,
1H), 7.79 (s, 1H), 8.14 (m, 1H), 8.38 (dd, 1H, J = 1.5,
4.9 Hz), 8.91 (s, 1H). 13C NMR (400 MHz, CD3OD) δ: 8.8,
8.9, 24.3, 24.5, 26.3, 28.0, 30.6, 31.3, 41.2, 41.3, 46.8, 51.7,
53.7, 69.3, 73.3, 75.1, 75.3, 90.3, 92.0, 117.2, 124.4, 130.9,
133.0, 138.8, 145.6, 147.0, 159.1. MS calcd. for C20H26N4O4:
386.2 (M+); found: 387.3.
cis-Oxazolidinone lactone (27e)
Following the same procedure as for compound 26e gave
27e in 65% yield. [α]D +36.5 (c 0.2, MeOH). IR (neat, cm–1):
cis-Oxazolidinone lactone (27a)
1
1748. H NMR (400 MHz, CD3OD) δ: 1.08 (t, 3H, J =
To a mixture of compound 26a (10 mg, 0.0328 mmol) and
4 Å molecular sieves (15 mg) in DCM (2 mL) was added
pyridinium chlorochromate (11 mg, 0.0492 mmol) under an
argon atmosphere and the mixture was stirred for 4 h at
room temperature. The mixture was filtered and processed
as usual to give a residue that was purified by column chro-
matography (EtOAc–hexanes, 4:6) to obtain compound 27a
as a crystalline solid (9 mg, 89%); mp 93 °C. [α]D +90.9 (c
6.9 Hz), 1.64 (m, 3H), 1.79 (m, 1H), 1.94 (m, 2H), 2.85 (m,
1H), 2.99 (m, 1H), 3.42 (m, 1H), 3.65 (m, 1H), 4.21 (m,
2H), 4.32–4.45 (m, 2H), 4.61 (m, 1H), 7.55 (m, 1H), 7.84 (s,
1H), 8.05 (s, 1H), 8.25 (m, 1H), 8.48 (m, 1H), 8.96 (s, 1H).
13C NMR (400 MHz, CD3OD) δ: 8.2, 24.3, 25.2, 27.8, 32.7,
41.6, 46.9, 51.7, 72.5, 79.6, 117.9, 134.1, 138.6, 144.8,
146.7, 157.9, 170.3. MS calcd. for C20H24N4O4: 384.2 (M+);
found: 385.3.
1
0.65, CHCl3). IR (KBr, cm–1): 1749. H NMR (400 MHz,
CDCl3) δ: 1.06 (t, 3H, J = 7.3 Hz), 1.78 (m, 1H), 1.87 (m,
3H), 2.53 (m, 1H), 2.66 (t, 1H, J = 7.4 Hz), 2.84 (dd, 1H,
J = 5.2, 14.5 Hz), 3.08 (m, 1H), 3.54 (m, 1H), 4.02 (m, 1H),
4.15 (m, 1H), 4.27 (t, 1H, J = 9.2 Hz), 7.15–7.34 (m, 5H).
13C NMR (400 MHz, CDCl3) δ: 9.5, 25.6, 29.1, 33.5, 34.0,
42.6, 51.2, 71.9, 79.4, 126.8, 128.7, 129.1, 141.1, 156.4,
168.9. MS calcd. for C17H21NO4: 303.1 (M+); found: 304.2.
Acknowledgements
We thank the Natural Sciences and Engineering Research
Council of Canada (NSERC) for financial assistance and
Ibis therapeutics (Carlsbad, California) for financial support
and antimicrobial tests. We also thank Michel Simard for the
X-ray crystal structures.
cis-Oxazolidinone lactone (27b)
Following the same procedure as for compound 26b gave
27b in 80% yield. [α]D +129 (c 0.3, CHCl3). IR (neat, cm–1):
1749. 1H NMR (400 MHz, CDCl3) δ: 0.84 (t, 3H, J =
8.2 Hz), 1.09 (t, 3H, J = 8.3 Hz), 1.31 (m, 8H), 1.59 (m,
2H), 1.79 (m, 1H), 1.99 (m, 1H), 2.62 (m, 1H), 3.02 (m,
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