First Total Synthesis of Trehalose-Containing Branched Oligosaccharide OSE-1 of Mycobacterium gordonae (Strain 990)

Article abstract of DOI:10.1002/chem.201502521

The first total synthesis of the branched oligosaccharide OSE-1 of Mycobacterium gordonae (strain 990) is reported. An intramolecular aglycon delivery approach was used for constructing the desymmetrized 1,1′-α,α-linked trehalose moiety. A [3+2] glycosylation of the trisaccharide donor and trehalose acceptor furnished the right hand side pentasaccharide. Regioselective O3 glycosylation of L-rhamnosyl 2,3-diol allowed expedient synthesis of the left hand side tetrasaccharide. The nonasaccharide was assembled in a highly convergent fashion through a [4+5] glycosylation. Take the strain: First total synthesis of the branched oligosaccharide OSE-1 of Mycobacterium gordonae (strain 990) is reported. An intramolecular aglycon delivery approach was used for constructing the desymmetrized 1,1′-α,α-linked trehalose moiety. Regioselective O3 glycosylation of L-rhamnosyl 2,3-diol allowed expedient synthesis of the left hand side tetrasaccharide. The nonasaccharide was assembled in a highly convergent fashion through a [4+5] glycosylation.

Full text of DOI:10.1002/chem.201502521

DOI: 10.1002/chem.201502521
Communication
&
Total Synthesis
First Total Synthesis of Trehalose-Containing Branched
Oligosaccharide OSE-1 of Mycobacterium gordonae (Strain 990)
[
a]
Manishkumar A. Chaube and Suvarn S. Kulkarni*
tant. The highly antigenic cell-wall components of the myco-
bacteria are potential candidates for serodiagnosis.
Abstract: The first total synthesis of the branched oligo-
saccharide OSE-1 of Mycobacterium gordonae (strain 990)
is reported. An intramolecular aglycon delivery approach
was used for constructing the desymmetrized 1,1’-a,a-
linked trehalose moiety. A [3+2] glycosylation of the tri-
saccharide donor and trehalose acceptor furnished the
right hand side pentasaccharide. Regioselective O3 glyco-
sylation of l-rhamnosyl 2,3-diol allowed expedient synthe-
sis of the left hand side tetrasaccharide. The nonasacchar-
ide was assembled in a highly convergent fashion through
a [4+5] glycosylation.
Over the past few years there have been remarkable advan-
[
8]
ces in the identification of bacterial glycans. In a recent study,
Seeberger and co-workers presented a comparative bioinfor-
matics analysis of the mammalian and bacterial glycomes in
which the most abundant bacterial monosaccharides and link-
[
9]
ages were statistically evaluated.
[
10]
In 1993, Besra et al. demonstrated that the basis of seror-
eactivity and diversity in M. gordonae is a novel series of alkali-
labile trehalose containing lipooligosaccharides (LOS). The
structure of the major branched oligosaccharide of M. gordo-
nae strain 990 was established as a-l-Rhap-(1!2)-3-O-CH -a-l-
3
Rhap-(1!3)-[b-d-Xylp-(1!2)-]-a-l-Rhap-(1!3)-b-d-Glcp-(1!3)-
Despite many decades of intense research, tuberculosis (Tb) re-
b-d-Glcp-(1!3)-a-l-Rhap-(1!3)-6-O-CH -a-d-Glcp-(1$1)-a-d-
3
[1]
mains one of the deadliest infectious diseases. Emergence of
Glcp and referred to as OSE-1 (Figure 1). The branched oligo-
[2]
[3]
multi-drug-resistant strains and its co-infection with HIV has
further complicated the Tb prognosis and treatment, making it
a leading public health risk worldwide. Moreover, during last
few years, it is being observed that diseases due to non-tu-
[4]
bercular mycobacteria (NTM) are on the rise. Especially in
AIDS patients, infections due to NTM are causing serious prob-
[5]
lems, which are incurable. Among various kinds of NTM iso-
lated from soil and water, Mycobacterium gordonae is an im-
portant one. Initially, M. gordonae was considered to be
a friendly bacterium but, due to the observed infections in pa-
tients with prosthetic devices, compromised immunity, chronic
pulmonary disease, or a history of trauma, it is considered as
[6]
a potential opportunistic respiratory tract pathogen. In addi-
tion, a number of infections involving skin, soft tissues, liver,
respiratory tract, and underlying immuno-suppression have
been reported. In particular, in the case of individuals with ad-
vanced immunodeficiency (such as AIDS) and who are suscep-
tible to a wide variety of microorganisms of low pathogenicity,
these infections cause pulmonary diseases virtually indistin-
guishable from Tb. Such patients are often started on antitu-
berculosis drugs such as isoniazid, pyrazinamide, ethambutol,
Figure 1. Structure of OSE-1 1 from Mycobacterium gordonae strain 990.
saccharide OSE-1 1 being antigenic can produce a specific
immune response in the host by developing specific antigens
and thereby allow a rapid serodiagnosis of the mycobacterial
infection. Thus, procurement of OSE-1 through chemical syn-
thesis is highly warranted.
Total synthesis of OSE-1 has not been reported to date, al-
though there are some advances towards this goal. Gurjar
et al. reported the synthesis of the terminal, branched tetrasac-
[6,7]
and cycloserine, to which M. gordonae is resistant.
To avoid
this confusion, the diagnosis of atypical mycobacteria is impor-
[
11]
charide of OSE-1. Misra and co-workers reported a linear syn-
[
12]
thesis of the heptasaccharide. However, these fragments lack
the biologically important 6’-OMe 1,1’-a,a-trehalose moiety. In
continuation of our studies towards the synthesis of trehalose
[
a] M. A. Chaube, Prof. Dr. S. S. Kulkarni
Department of Chemistry
Indian Institute of Technology Bombay
Powai, Mumbai, 400076 (India)
E-mail: suvarn@chem.iitb.ac.in
[13]
glycoconjugates, herein we report the first total synthesis of
OSE-1.
A major challenge involved in the synthesis of OSE-1 is the
construction of the unsymmetrically substituted 1,1’-a,a-treha-
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201502521.
Chem. Eur. J. 2015, 21, 13544 – 13548
13544
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
lose disaccharide bearing a methyl group at one of the termini.
Moreover, the methyl group bearing a d-glucopyranoside unit
should also be equipped with a temporary protecting group at
the O3’ position so that it can be selectively removed prior to
attachment with the l-rhamnose end of the oligosaccharide.
There are a few methods reported in the literature for con-
constructed by a [4+5] glycosylation between the tetrasac-
charide thioglycoside donor 2 and the pentasaccharide accept-
or 3. The pentasaccharide could be synthesized by a [3+2] gly-
cosylation between the trisaccharide thioglycoside donor 4
and the 6’-OMe trehalose acceptor 5, which in turn could be
synthesized from d-glucose-derived building blocks 6 and 7
employing the IAD reaction. The trisaccharide donor 4 could
be obtained by glycosylation of monosaccharide building
blocks 8 and 9. The terminal tetrasaccharide donor 2 could be
assembled starting from the monosaccharide building blocks
10, 11, 12, and 13 through sequential couplings.
[14–16]
structing the 1,1’-a,a-glycosidic bond.
However, most of
the methods are limited by poor anomeric selectivity of the
glycosylation step, as not one but two anomeric linkages are
formed simultaneously and four products are possible in the
case of unsymmetrical derivatives. To tackle this problem, Ber-
tozzi and co-workers reported for the first time a methodology
for the synthesis of 1,1’-a,a-trehalose derivatives, using Ito’s
Our synthesis began with the construction of the unique
1,1’-a,a-trehalose acceptor
5
through the IAD route
[
17]
[16]
variant
of intramolecular aglycon delivery (IAD).
In this
(Scheme 2). For this purpose, the known 3-O-allyl diacetone
[
19]
method, the glucosyl donor and acceptor molecules are oxida-
tively tethered and oriented prior to activation in such a way
that only the desired 1,1’-a,a-stereoisomer can be formed. This
elegant method is so far the best among all the existing meth-
ods for the formation of unsymmetrically substituted 1,1’-a,a-
trehalose derivatives. Alternatively, one can use commercially
available trehalose. However, regioselective differentiation of
glucose 14, obtained by allylation of diacetone glucose, was
converted into its pyranose form thioglycoside 15 in three
steps (55% overall) through acid hydrolysis of the acetonides,
per-O-acetylation, and concomitant nucleophilic displacement
of the anomeric acetate by ethanethiol. Removal of acetates in
15 using NaOMe in MeOH and benzylidene protection of the
4,6-diol furnished the suitably protected 2-OH derivative 6 in
chemically similar, six secondary hydroxyl groups, in the C
88% yield over two steps. The key IAD reaction of 6 and easily
2
18]
[
[16a]
symmetrical, non-reducing disaccharide is again a challenge.
Owing to its convergent nature and exclusive stereoselectivity,
accessible a-linked dimethoxybenzyl (DMB) glycoside 7
was
conducted next. Compound 6 was first linked with 7 by oxida-
tion of the DMB ether using 2,3-dichloro-5,6-dicyano-1,4-ben-
zoquinone (DDQ) to form the mixed acetal 16, which upon
aqueous work up was subsequently activated using methyl tri-
[
16]
the IAD method seemed more appropriate for our purpose.
Our retrosynthetic strategy entailed a convergent assembly
of the nonasaccharide, as shown in Scheme 1. It was envisaged
that the target molecule 1 could be obtained upon global de-
protection from its fully protected precursor, which could be
[
16b]
fluoromethanesulfonate
to afford the unsymmetrically sub-
stituted 1,1’-a,a-trehalose derivative 17 exclusively in 58%
yield over two steps. The stereo-
chemistry of the newly installed
glycosidic linkage in 17 was as-
1
13
signed through H, C, and 2D
1
NMR. The H NMR spectrum of
1
7
showed two overlapping
doublets for 1H each at d=5.19
J=2.8 Hz) and 5.18 ppm (J=
(
3
1
.1 Hz) corresponding to the H-
13
and H-1’ of trehalose. C NMR
spectrum of 17 showed two sep-
arate peaks for the 1,1’-linked
glucosides at d=95.3 and
1
9
3.8 ppm with characteristic J
CH
coupling constants of 170 and
69 Hz, respectively, confirming
the a,a-linkage (see the Sup-
1
[
20]
porting Information). The free
hydroxyl group in 17 was pro-
tected as benzyl ether to afford
the fully protected trehalose
building block 18 (benzyl bro-
mide, NaH, 82%). A regioselec-
tive reductive ring opening of
the 4,6-O-benzylidene acetal in
[
13b,21]
18 using DIBAL-H
in tolu-
ene furnished the primary alco-
Scheme 1. Retrosynthetic analysis of OSE-1 1.
hol 19 (68%), as a major isomer
Chem. Eur. J. 2015, 21, 13544 – 13548
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13545
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Communication
Scheme 2. Synthesis of unsymmetrically substituted 1,1’-a,a-trehalose using
IAD reaction.
along with a minor 4-OH isomer (13%) and recovered starting
material 18 (17%), which was recycled. Compound 19 was
subsequently methylated using methyl iodide and NaH as
a base to afford 6’-OMe derivative 20 (93%). The O-allyl group
in 20 was selectively cleaved with palladium chloride and
sodium acetate to furnish the desired 3’-OH trehalose acceptor
Scheme 3. Synthesis of pentasaccharide acceptor 3.
[
22]
disaccharide 23 in 94% yield. The characteristic NMR signals
1
13
5
in 85% yield.
[ H NMR d=4.73 ppm (d, 1H, J=7.8 Hz, H-1b), C NMR d=
101.4 ppm] confirmed the b-linkage of the newly formed gly-
cosidic bond in 23. Next, the 2-naphthylmethyl group in 23
was selectively cleaved using DDQ to afford the disaccharide
acceptor 24 in 68% yield, which was again coupled with the
donor 8 using TMSOTf (0.35 equiv) as a promoter to furnish
the b-linked trisaccharide donor 4 in 64% yield. Here, the yield
could not be further improved because of the competing for-
mation of the corresponding orthoester, which could not be
rearranged even after adding 0.5 equiv of TMSOTf. The struc-
With the requisite right hand side trehalose unit in hand, we
proceeded further to assemble the pentasaccharide fragment
Scheme 3). For this, the trisaccharide skeleton was first con-
structed starting from the known 3-O-naphthylmethyl diace-
(
[
23]
tone glucose 21. Acid hydrolysis of both the isopropylidene
[
16b]
groups in 21, to switch from furanose to pyranose form,
fol-
lowed by benzylidene protection of 4,6-diol and 1,2-di-O-acety-
lation, afforded compound 22 in 78% yield over three steps.
The anomeric acetate in 22 was selectively removed by ammo-
[
24]
1
nium carbonate in 64% yield, with recovery of the starting
material to the extent of 30%. The resulting hemiacetal was
converted quantitatively into the trichloroacetimidate (TCA)
ture of trisaccharide 4 was confirmed by NMR analysis [ H d=
4.75 (d, 1H, J=7.7 Hz, H-1b), 4.66 (d, 1H, J=7.2 Hz, H-1b),
13
5.41 ppm (s, 1H, H-1a), C NMR d=101.1, 100.9, 85.6 ppm].
Next, the thioglycoside donor 4 and the trehalose acceptor 5
were glycosylated under NIS and TMSOTf conditions to furnish
the pentasaccharide 25 in 84% yield. The 1,2-trans selectivity
in these three consecutive glycosylations was assured by
neighboring group participation of the C2-acetate groups. The
[
25]
donor 8 using trichloroacetonitrile and potassium carbonate.
Glycosylation of TCA donor 8 with the known l-rhamnose
[
26]
acceptor 9 using 0.1 equiv of trimethylsilyl trifluoromethane-
sulfonate (TMSOTf) as a promoter resulted in the formation of
1
:1 mixture of the desired product 23 and the corresponding
1
13
orthoester, which could be rearranged to the product 23 upon
adding extra 0.15 equiv TMSOTf to the mixture. Alternatively,
the use of 0.25 equiv of TMSOTf smoothly delivered b-linked
structure was assigned by H NMR, C NMR and calculation of
1
13
JCH through a partially decoupled C NMR experiment and
13
HSQC correlation. We observed six peaks in C NMR in the
Chem. Eur. J. 2015, 21, 13544 – 13548
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13546 ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
1
3
range d=101.4–94.0 ppm, which included a tall peak corre-
sidic linkages. In its C NMR spectrum, two peaks were ob-
1
sponding to two benzylidenes (d=101.2 ppm, J =158) and
served in the anomeric region at d=101.4 and 85.7 ppm with
CH
1
1
1
five anomeric carbons at d=101.4 ( J =160, b), 100.9 ( J
=
characteristic coupling constants J =174 and 165 Hz, respec-
CH
CH
CH
1
1
[11,31]
1
55, b), 97.6 ( J =171, a), 94.8 ( J =171, a), and 94.0 ppm
tively confirming a-configurations for C1’ and C1.
accharide thioglycoside 26 was then treated with NBS
THF:H O to yield the corresponding disaccharide hemiacetal
The dis-
CH
CH
1
[32]
(
JCH =168, a). The 2-naphthylmethyl group in 25 was selec-
in
[
27]
tively removed using DDQ at pH 7 to afford the pentasac-
charide acceptor 3 in 62% yield. It should be mentioned that
the use of phosphate buffer was essential, without which the
yield of 3 dropped to 25%.
2
(96%), which was converted to the TCA donor 27 (93%, a/b=
1:0.8). A highly regioselective orthogonal glycosylation of TCA
[
28]
donor 27 with the known 2,3-diol 10 under controlled con-
ditions (0.1 equiv TMSOTf and addition at À208C) afforded the
desired 3-O-linked trisaccharide 28 in 85% yield as a single
product. The regioselectivity of the glycosylation step was con-
firmed by capping the free 2-OH by chloroacetate group and
observing the downfield shift of the characteristic H-2 peak
After successfully synthesizing the pentasaccharide frag-
ment, we proceeded further to assemble the left-hand tetra-
saccharide part, starting from the nonreducing end to the re-
ducing end. As shown in Scheme 4, the known l-rhamnosyl
[
28]
2
,3-diol 10 was converted into its tin acetal by using dibutyl-
1
tin oxide in toluene at 1108C, which was further reacted with
(d=5.46 ppm, dd, J=1.6 and 2.8 Hz) in the H NMR of 28a,
1
1
assigned through H- H COSY analysis. The H-3 proton gave an
upfield dd at d=4.10 ppm with J=3.0 and 9.6 Hz. The a-ste-
reoselectivity was further confirmed by recording a partially
13
decoupled C NMR spectrum of 28 and calculating the CH
coupling constant of the newly formed glycosidic bond. The
1
3
C NMR spectrum of 28 showed peaks at d=101.0, 99.2, and
1
8
7.4 ppm with JCH coupling constants of 168, 168, and
1
66 Hz, respectively, confirming three consecutive a-linkag-
[
11,31]
es.
The branching unit d-xylose was then introduced at
the O2 position of l-rhamnose by glycosylation of the known
[
33]
2
,3,4-tri-O-acetyl-d-xylose TCA donor 11 with the trisacchar-
ide acceptor 28 using 0.35 equiv TMSOTf to afford the desired
1
b-xylose linked tetrasaccharide 2 (62%). Peaks in H NMR at
13
d=4.76 ppm(d, 1H, J=7.5 Hz, H-1b) and C NMR peak at d=
02.4 ppm confirmed the b-glycosidic linkage of the newly
1
formed bond.
The assembly of nonasacharide OSE-1 and final deprotection
was carried out as shown in Scheme 5. The tetrasaccharide thi-
oglycoside donor 2 was glycosylated with the pentasaccharide
acceptor 3 under NIS and TMSOTf conditions to afford the
fully protected nonasaccharide 29 in 68% yield. The structure
1
13
of nonasaccharide was assigned by H NMR, C NMR, and cal-
1
13
1
culation of J through a CÀ H coupled HSQC experiment on
CH
a 750 MHz machine, which showed a total of eleven carbon in
the d=94–103 ppm range, including nine anomeric carbons
1
(
3b and 6a) and two benzylidene carbons at d=94.0 ( J
=
CH
Scheme 4. Synthesis of tetrasaccharide donor 2.
methyl iodide and catalytic tetrabutylammonium iodide in
DMF to afford the 3-O-methylated compound 12 in excellent
[29]
yield and regioselectivity (98%). The O3 regioselectivity was
confirmed by carrying out acetylation of 12 and observing
1
a downfield shift of the H2 proton in the H NMR spectrum
1
(
1
d=5.44 ppm, dd, J=1.6 and 3.2 Hz), assigned through H-
[30]
H COSY analysis. The known TCA donor 13 and the 2-OH ac-
ceptor 12 were orthogonally glycosylated using TMSOTf as
a promoter to afford the a-linked disaccharide 26 in 98%
1
yield. The H NMR of 26 displayed two downfield doublets at
d=5.47 and 5.01 ppm with J=1.5 Hz each, indicating a-glyco-
Scheme 5. Synthesis of target molecule OSE-1 1.
Chem. Eur. J. 2015, 21, 13544 – 13548
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13547 ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
1
1
1
74 Hz, a), 94.7( J =173 Hz, a), 97.6 ( J =179 Hz, a), 99.2
[5] L. G. Wayne, H. A. Sramek, Clin. Microbiol. Rev. 1992, 5, 1–25.
[6] T. W. Barber, D. E. Craven, H. W. Farber, Chest 1991, 100, 716–720.
CH
CH
1
1
1
(
JCH =178 Hz, a), 100.0 ( J =167 Hz, b), 101.0 ( J =166 Hz,
CH CH
[7] T. M. Stine, A. A. Harris, S. Levin, N. Rivera, R. L. Kaplan, JAMA J. Am. Med.
1
1
PhCH), 101.3 ( J =176 Hz, a), 101.2 ( J =173 Hz, a), 101.7
CH
CH
Assoc. 1987, 258, 809–811.
1
1
(
(
JCH =164 Hz, b), 102.0 ( J =167 Hz, PhCH), and 102.4 ppm
[8] V. N. Tra, D. H. Dube, Chem. Commun. 2014, 50, 4659–4673.
[9] A. Adibekian, P. Stallforth, M.-L. Hecht, D. B. Werz, P. Gagneux, P. H. See-
berger, Chem. Sci. 2011, 2, 337–344.
10] G. S. Besra, M. R. McNeil, K.-H. Khoo, A. Dell, H. R. Morris, P. J. Brennan,
Biochemistry 1993, 32, 12705–12714.
[11] M. K. Gurjar, S. Adhikari, Tetrahedron 1997, 53, 8629–8634.
CH
1
1
13
1
JCH =167 Hz, b). The H detected CÀ H coupled HSQC ex-
periment (see the Supporting Information) allowed us to calcu-
late the CÀH coupling constants at a lower concentration and
in much lesser time which was not possible with a standard
[
13
one dimensional C-detected partial decoupling experiment
due to significant overlapping of peaks. Using this technique,
[12] R. Panchadhayee, A. K. Misra, Glycoconjugate J. 2008, 25, 817–826.
[
13] a) V. A. Sarpe, S. S. Kulkarni, J. Org. Chem. 2011, 76, 6866–6870; b) V. A.
Sarpe, S. S. Kulkarni, Org. Biomol. Chem. 2013, 11, 6460–6465; c) V. A.
Sarpe, S. S. Kulkarni, Org. Lett. 2014, 16, 5732–5735.
1
slightly higher values of JCH coupling constants (approx. 4 Hz)
were observed, which were consistent.
[14] For a review on 1,1’-glycosylation, see: M. A. Chaube, S. S. Kulkarni,
Trends Carbohydr. Res. 2012, 4, 1–19.
Global deprotection of nonasaccharide 29 was carried out in
two steps; hydrogenation in the presence of palladium hydrox-
ide in 50% acetic acid removed the benzyls and benzylidene
[
15] Selected papers on 1,1’-glycosylation: a) J. Yoshimura, K. Hara, T. Sato,
H. Hashimoto, Chem. Lett. 1983, 319–320; b) M. Nishizawa, D. M.
Garcia, Y. Noguchi, K. Komatsu, S. Hatakeyama, H. Yamada, Chem.
Pharm. Bull. 1994, 42, 2400–2402; c) T. E. C. L. Ronnow, M. Meldal, K.
Bock, Tetrahedron: Asymmetry 1994, 5, 2109–2122; d) L. Cipolla, L. Lay,
F. Nicotra, L. Panza, G. Russo, Tetrahedron Lett. 1994, 35, 8669–8670;
e) G. H. Posner, D. S. Bull, Tetrahedron Lett. 1996, 37, 6279–6282; f) K. C.
Nicolaou, F. L. van Delft, S. R. Conley, H. J. Mitchell, Z. Jin, R. M. Rodrí-
guez, J. Am. Chem. Soc. 1997, 119, 9057–9058.
[
34]
protecting groups,
whereas the acetates were removed
using sodium methoxide. Subsequent chromatographic purifi-
cation using a Sephadex G-25 column in MeOH/water system
afforded the target molecule OSE-1 1 (77% over two steps).
In conclusion, we have reported the first total synthesis of
oligosaccharide OSE-1 of M. gordonae (strain 990) in a highly
convergent manner. The potent desymmetrized trehalose
moiety with 6’-OMe functionality was prepared using intramo-
lecular aglycon delivery method. In the course of our studies,
we also explored a highly O3 regioselective glycosylation of l-
rhamnosyl 2,3-diol. The target molecule can be used for the
speedy serodiagnosis of the infection and for the development
of the vaccine candidate against M. gordonae.
[16] IAD approach for trehalose: a) M. R. Pratt, C. D. Leigh, C. R. Bertozzi, Org.
Lett. 2003, 5, 3185–3188; b) C. D. Leigh, C. R. Bertozzi, J. Org. Chem.
2008, 73, 1008–1017.
[17] Y. Ito, H. Ando, M. Wada, T. Kawai, Y. Ohnish, Y. Nakahara, Tetrahedron
2001, 57, 4123–4132.
[18] V. A. Sarpe, S. S. Kulkarni, Trends Carbohydr. Res. 2013, 5, 8–33.
[
[
[
19] R. Lakhmiri, P. Lhoste, D. Sinou, Tetrahedron Lett. 1989, 30, 4669–4672.
20] K. Bock, C. Pedersen, J. Chem. Soc. Perkin Trans. 2 1974, 293–297.
21] N. Tanaka, I. Ogawa, S. Yoshigase, J. Nokami, Carbohydr. Res. 2008, 343,
2675–2679.
[
[
22] G. J. S. Lohman, P. H. Seeberger, J. Org. Chem. 2004, 69, 4081–4093.
23] J. Xia, S. A. Abbas, R. D. Locke, C. F. Piskorz, J. L. Alderfer, K. L. Matta, Tet-
rahedron Lett. 2000, 41, 169–173.
Acknowledgements
[
[
24] M. Mikamo, Carbohydr. Res. 1989, 191, 150–153.
25] a) R. R. Schmidt, J. Michel, Tetrahedron Lett. 1984, 25, 821–824; b) R. R.
Schmidt, W. Kinzy in Advances in Carbohydrate Chemistry and Biochem-
istry, Vol. 50 (Ed.: D. Horton), Academic Press, San Diego, 1994, p. 21.
We thank the Department of Science and Technology (Grant
No. SR/S1/OC-40/2009), the Board of Research in Nuclear Scien-
ces (Grant No. 2013/37C/51/BRNS), IRCC, IITB (09IRCC001) for fi-
nancial support. MAC thanks CSIR-New Delhi for a fellowship.
We thank the Highfield 750 MHz NMR facility at IIT Bombay
funded by RIFC, IRCC. Special thanks to Dr. Ashutosh Kumar
for his help in suggesting and recording the HSQC experiment
for the nonasaccharide.
[26] H. M. Zuurmond, S. C. van der Laan, G. A. van der Marel, J. H. van Boom,
Carbohydr. Res. 1991, 215, C1–C3.
[
[
27] M. A. Walczak, S. J. Danishefsky, J. Am. Chem. Soc. 2012, 134, 16430–
6433.
28] V. Pozsgay, J. Org. Chem. 1998, 63, 5983–5999.
1
[29] D. Crich, Q. Yao, J. Am. Chem. Soc. 2004, 126, 8232–8236.
[
[
[
30] A. M. P. van Steijn, J. P. Kamerling, J. F. G. Vliegenthart, Carbohydr. Res.
991, 211, 261–277.
1
31] E. S. H. El Ashry, N. Rashed, E. S. I. Ibrahim, Tetrahedron 2008, 64, 10631–
10648.
32] P. Wang, H. Lee, M. Fukuda, P. H. Seeberger, Chem. Commun. 2007,
Keywords: 1,1’-a,a-glycosylation
Mycobacterium gordonae
·
total
synthesis
·
·
· regioselective glycosylation
1963–1965.
trehalose oligosaccharides
[
[
33] G. Gu, Y. Du, R. J. Linhardt, J. Org. Chem. 2004, 69, 5497–5500.
34] a) M. N. Amin, W. Huang, R. M. Mizanur, L.-X. Wang, J. Am. Chem. Soc.
[
[
1] A. Koul, E. Arnoult, N. Lounis, J. Guillemont, K. Andries, Nature 2011,
69, 483–490.
2] R. Johnson, E. M. Streicher, G. E. Louw, R. M. Warren, P. D. van Helden,
T. C. Victor, Curr. Issues Mol. Biol. 2006, 8, 97–112.
2
2
011, 133, 14404–14417; b) S. R. Sanapala, S. S. Kulkarni, Chem. Eur. J.
014, 20, 3578–3583.
4
[
[
3] C. K. Kwan, J. D. Ernst, Clin. Microbiol. Rev. 2011, 24, 351–376.
4] R. J. Wallace Jr, B. A. Brown, D. E. Griffith, Annu. Rev. Microbiol. 1998, 52,
Received: June 29, 2015
4
53–490.
Published online on August 6, 2015
Chem. Eur. J. 2015, 21, 13544 – 13548
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