Synthesis of a β-GlcN-(1→4)-MurNAc building block en route to N-deacetylated peptidoglycan fragments

Article abstract of DOI:10.1016/j.tetlet.2009.12.124

Some bacteria present a variation in their peptidoglycan structure that is the absence of the N-acetyl substituent in the glucosamine residue. Very recently, this structural modification was demonstrated to be critical for host innate immune evasion in Listeria monocytogenes. To shed light on the molecular details of the evasion mechanism, the synthesis of some N-deacetylated peptidoglycan fragments is needed. En route to this goal a high-yielding synthesis of a GlcN-MurNAc disaccharide building block has been accomplished. A careful study of the optimal protecting groups and reaction conditions was done to have a complete β-stereoselectivity in glycosylation as well as to ensure a high versatility to the disaccharide building block.

Full text of DOI:10.1016/j.tetlet.2009.12.124

Tetrahedron Letters 51 (2010) 1117–1120
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of a b-GlcN-(1?4)-MurNAc building block en route to N-deacetylated
peptidoglycan fragments
*
Luigi Cirillo, Emiliano Bedini , Antonio Molinaro, Michelangelo Parrilli
Dipartimento di Chimica Organica e Biochimica, Università di Napoli ‘‘Federico II”, Complesso Universitario Monte S.Angelo, Via Cintia 4, 80126, Napoli, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Some bacteria present a variation in their peptidoglycan structure that is the absence of the N-acetyl sub-
stituent in the glucosamine residue. Very recently, this structural modification was demonstrated to be
critical for host innate immune evasion in Listeria monocytogenes. To shed light on the molecular details
of the evasion mechanism, the synthesis of some N-deacetylated peptidoglycan fragments is needed. En
route to this goal a high-yielding synthesis of a GlcN–MurNAc disaccharide building block has been
accomplished. A careful study of the optimal protecting groups and reaction conditions was done to have
a complete b-stereoselectivity in glycosylation as well as to ensure a high versatility to the disaccharide
building block.
Received 12 October 2009
Revised 17 December 2009
Accepted 21 December 2009
Available online 29 December 2009
Keywords:
Peptidoglycan
Muramic acid
Glucosamine
Glycosylation
Ó 2009 Elsevier Ltd. All rights reserved.
Peptidoglycan is an essential and unique structural part of the
bacterial cell wall. It has a polymeric structure with alternating
N-acetyl-glucosamine (GlcNAc) and N-acetyl-3-O-(R)-lactyl-gluco-
samine (muramic acid, MurNAc) linked through b-1?4-bonds. The
lactyl moiety of MurNAc is covalently attached to a pentapeptide
chain that is employed in polymer cross-linking.1 Structural mod-
ifications in the glycan strand often affect bacterial recognition by
hosts.2 One of the most common modifications is N-deacetylation.
It has been recently demonstrated that the absence of N-acetyl
substituent in the glucosamine residue of peptidoglycans from
Listeria monocytogenes—a Gram-positive human intracellular
pathogen—is critical for the bacterium to evade the host innate im-
mune system, survive in gastrointestinal environment and dissem-
inate to various organs by surviving in human macrophages.3 The
mechanism of immune system evasion seems to be based on a pro-
tection against the bacteriolytic activity of lysozyme as well as on
escaping Toll-like receptor (TLR)-2 and nucleotide-binding oligo-
merization domain (Nod)-1 and 2 protein detection, even if no
molecular details have been reported yet. N-Deacetylation at GlcN
site was also found in some other bacteria, among which Xantho-
knowledge, there was no report on the synthesis of N-deacety-
lated-GlcN-containing structures, in spite of the interest in unrav-
eling the molecular details of innate immune evasion. For this
reason and in light of our interest in the chemical synthesis and
phytopathological study of MAMP-related compounds,6 we
embarked in the synthesis of peptidoglycan fragments containing
N-deacetylated glucosamine units. En route to this goal, the syn-
thesis of a highly versatile b-GlcN-(1?4)-MurNAc building block
is reported in this work.
The known syntheses of peptidoglycan fragments all necessi-
tated to introduce the acetamido moiety before the coupling with
the peptide chain.5 This strategy cannot be applied to the synthesis
of peptidoglycan fragments with a N-deacetylated GlcN unit.
Therefore, GlcN and MurN nitrogen atoms had to be protected with
orthogonal protecting groups, the GlcN one being able to liberate
the amine at the final stage of the synthesis. Moreover, since the
global aim of our total synthesis is the obtention of not only
peptidodisaccharide fragments but also higher oligomers, the ano-
meric position of MurNAc unit and the position 4 of GlcN had to be
protected with orthogonal protecting groups too. Finally, the even-
tuality of side-reactions involving the (R)-lactyl moiety during the
manipulation of MurNAc building blocks (racemization, intramo-
lecular lactonization at 4-hydroxy position),7 suggested to intro-
duce the lactyl ether at a late stage in the synthesis. All these
constrains designed A as a proper disaccharide building block
(Scheme 1). It could be obtained by a stereoselective coupling
between suitably protected GlcN acceptor B and donor C.
monas campestris,4
a Gram-negative phytopathogen causative
agent of black-rot, a disease of cruciferous plants of worldwide
importance.
In the last decade there was a great deal of activity directed to-
ward the chemical synthesis of several peptidoglycan fragments,5
because of the lack of pure and discrete species for precise struc-
tural and biochemical studies. Nonetheless, to the best of our
The glycosylation of a 4-hydroxy group in glucosamine accep-
tors presents some well-known difficulties related to its low nucle-
ophilicity.8 Some methods were reported to address this problem;9
* Corresponding author. Tel.: +39 81 674153; fax: +39 81 674393.
E-mail address: ebedini@unina.it (E. Bedini).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.12.124

1118
L. Cirillo et al. / Tetrahedron Letters 51 (2010) 1117–1120
oselectivity. These are very usually amido-, carbamato- or imido-
protecting groups. Unfortunately they could present some prob-
lems here in surviving as stable protecting groups—that is, during
the cleavage of oxazolidinone—and/or in their final deprotection to
free amine in the presence of the peptide chain. To avoid any pro-
tecting group interconversion at a disaccharide level, an azide was
selected as amino-masking group. Even if azide is incapable of
neighboring group participation, it can be easily transformed into
a free amine during final hydrogenolysis deprotecting step.
The known compound 112 was prepared in three steps from
N-acetyl-glucosamine and served as key building block for the syn-
thesis of both acceptor 4 and donor 7 (Scheme 2). A portion of 1
was treated with triphosgene13 to give oxazolidinone 2 in 60%
yield. Subsequent N-acetylation (92%) and regioselective benzyli-
dene ring opening under reductive conditions (Et3SiH/TFA in
CH2Cl2; 57%) afforded acceptor 4. Conversely, the treatment of 1
with triflyl azide in pyridine14 and subsequent benzylation of the
3-hydroxy group gave 5 (71% over two steps), which was de-O-
Scheme 1. Protecting group pattern on glycosyl donor, acceptor, and disaccharide.
allylated with PdCl2 (58%) and then converted into the a-trichloro-
among these protocols, we firstly focused our attention on the use
of
acceptor.
acetimidate donor 7. Unfortunately the coupling between 4 and 7
in a b-directing nitrile solvent gave no disaccharide (Table 1, en-
tries 1 and 2). Given the torsional and electronic disarming effect
of a 4,6-benzylidene protection on glycosyl donors,15 a more reac-
tive 2-azido-2-deoxyglucosyl donor was synthesized, having a
benzyl at position 6 and a selectively cleavable p-methoxybenzyl
group at position 4. It was obtained in four steps from 5 (Scheme
a
N-acetyl-2,3-oxazolidinone protection10 on the glycosyl
Several building blocks were developed as glycosyl donors for
the stereoselective synthesis of b-2-amino-2-deoxyglucosides.11
They generally present a N-2 protecting group capable of efficient
participation via acyloxonium ion that guarantees 1,2-trans stere-
Scheme 2. Reagents and conditions: (a) Ref. 13; (b) triphosgene, 2:1 v/v CH3CN/satd aq NaHCO3, rt, 60%; (c) AcCl, DIPEA, CH2Cl2, rt, 92%; (d) Et3SiH, TFA, AW-300 4 Å MS,
CH2Cl2, 5 °C, 57% for 4, 74% for 8, 77% for 13; (e) (i) TfN3, CuSO4, Et3N, py, 0 °C; (ii) BnBr, NaH, DMF, rt, 71% over two steps; (f) PdCl2, 1:1 v/v CH2Cl2/MeOH, rt, 58% for 6, 80% for
10; (g) Cl3CCN, DBU, CH2Cl2, rt, 78% for 7, 70% for 11; (h) PMBCl, NaH, DMF, 0 °C, 92%; (i) (i) TrocCl, NaHCO3, 2:1 H2O/CH3CN, rt; (ii) CbzCl, DMAP, CH2Cl2, rt, 70% over two
steps.

L. Cirillo et al. / Tetrahedron Letters 51 (2010) 1117–1120
1119
Table 1
Glycosylation reaction
Entry
Acceptor
Donora
Promoterb
Solvent
T
Disaccharide productc (Yield)
1
2
3
4
4
4
4
4
13
13
13
13
13
7
7
11
11
11
7
11
11
11
11
TMSOTf (0.02 equiv)
TMSOTf (0.2 equiv)
TMSOTf (0.02 equiv)
BF3ÁOEt2 (0.6 equiv)
BF3ÁOEt2 (0.15 equiv)
BF3ÁOEt2 (0.2 equiv)
BF3ÁOEt2 (0.2 equiv)
BF3ÁOEt2 (0.2 equiv)
BF3ÁOEt2 (0.2 equiv)
TMSOTf (0.02 equiv)
CH3CN
CH3CN
Pivalonitrile
3:2 v/v CH2Cl2/hexane
3:2 v/v CH2Cl2/hexane
3:2 v/v CH2Cl2/hexane
3:2 v/v CH2Cl2/hexane
3:2 v/v CH2Cl2/hexane
3:2 v/v CH2Cl2/CH3CN
3:2 v/v CH2Cl2/hexane
À20 °C
rt
rt
No reaction
14 (traces)d
15 (traces)d
4
À30 °C
À60 °C
À78 °C
À78 °C
À30 °C
À30 °C
À78 °C
15 (68%; b/
15 (68%; b/
a
a
1:1)e
5f
6
1:3:1)e
16 (16%; only b)e
17 (81%; only b)e
17 (40%; only b)e
17 (43%; only b)e
7
8
9
10
17 (71%; a
/b 4:1)e
a
b
c
d
e
f
Donor/acceptor molar ratio = 1.6, unless otherwise stated.
Promoter equivalents calculated with respect to the donor.
Isolated yield, unless otherwise stated.
Detected by TLC and MALDI analysis.
Anomeric ratio measured by the isolation of two anomers.
Donor/acceptor molar ratio = 2.3.
2). Regioselective reductive opening of the benzylidene ring gave 8
(74%), that was then treated with PMBCl and NaH to afford 9 in 92%
yield. De-O-allylation (80%) and subsequent treatment with
imido-protecting groups.17 Compound 13 was synthesized from
key building block 1 by N-trichloroethoxycarbonylation and pro-
tection of the 3-hydroxy as Cbz to give 12 (70% over two steps),
which was then subjected to Et3SiH/TFA benzylidene ring opening
(77%) (Scheme 2). The coupling between 13 and 7 was unsatisfying
(entry 6), whereas the glycosylation between 13 and 11 under
BF3ÁOEt2 catalysis in a CH2Cl2 solvent system at À78 °C afforded
disaccharide 1718 in good yield (81%) and complete b-stereoselec-
tivity (Table 1, entry 7). Such SN2 reaction conditions guarantee all
together a high yield of 17b. A higher temperature, a more polar
solvent system or a stronger activator considerably reduced the
yield of 16b (entries 8–10). Disaccharide 17b is a highly versatile
building block. Indeed, it was readily transformed into alcohol 18
by cleavage of Troc- and Cbz-protecting groups with 2 M KOH
and subsequent N-acetylation (67% over two steps) (Scheme 3).
Lactylation was then performed with the triflate of ethyl (S)-lacta-
te5j and NaH in CH2Cl2 to give 1918 (61%). GlcN–MurNAc deprotec-
ted disaccharide was obtained as ethyl ester by hydrogenolysis
(65%). Moreover, an access to a disaccharide donor and acceptor
Cl3CCN and DBU afforded the desired
a-trichloroacetimidate 11
in 70% yield. Again, the reaction of 4 and 11 in nitrile solvent gave
no coupling (entry 3). Some scattered examples in the literature re-
port the b-glycosylation of 2-azido-2-deoxyglycosyl-a-trichloro-
acetimidates under SN2 conditions.16 Therefore, the coupling
between 4 and 11 was attempted at low temperature in a
CH2Cl2–hexane solvent mixture with BF3ÁOEt2 as catalyst (entry
4). Disaccharide 15 was obtained in 68% yield, but without any ste-
reoselectivity. Higher donor/acceptor molar ratio and even milder
activation conditions gave the same yield with an only slight
excess of b-anomer (entry 5).
The low b/a stereoselectivity is not really surprising for glycosy-
lations involving 2,3-oxazolidinone GlcN acceptors.9 Therefore, a
new glycosyl acceptor (13) was designed, with the amino group
protected as a trichloroethoxycarbamate (Troc), which affords
greater GlcN-4-hydroxy reactivity than other carbamato- or
Scheme 3. Reagents and conditions: (a) (i) 5:1 v/v THF/2 M aq KOH, 50 °C; (ii) 10:10:1 v/v/v CH2Cl2/MeOH/Ac2O, rt, 67% over two steps; (b) ethyl (S)-2-
(trifluoromethanesulfonyloxy)propionate, NaH, CH2Cl2, rt, 61%; (c) Pd/C, 9:1 v/v MeOH/HCOOH, ultrasound bath, 40 °C, 65%.

1120
L. Cirillo et al. / Tetrahedron Letters 51 (2010) 1117–1120
8. (a) Paulsen, H. Angew. Chem., Int. Ed. Engl. 1982, 21, 155–173; (b) Crich, D.;
Dudkin, V. J. Am. Chem. Soc. 2001, 123, 6819–6825; (c) Liao, L.; Auzanneau, F.-I.
Org. Lett. 2003, 5, 2607–2610; (d) Lucas, R.; Hamza, D.; Lubineau, A.; Bonnaffé,
D. Eur. J. Org. Chem. 2004, 2107–2117.
9. Crich, D.; Vinod, A. U. J. Org. Chem. 2005, 70, 1291–1296. and references cited
therein.
can be opened from 17b by cleaving selectively the allyl and p-
methoxybenzyl, respectively. This work is currently in progress
en route to the synthesis of L. monocytogenes and X. campestris pep-
tidoglycan disaccharide and tetrasaccharide fragments.
In conclusion, the synthesis of a highly versatile GlcN–MurNAc
building block was reported. Since glycosylation presented several
difficulties and constrains (low reactivity at position 4 of GlcN
acceptors; necessity of gain 1,2-trans stereoselectivity without
the use of amido-, imido-, or carbamato-neighboring protecting
group; a protecting group pattern suitable for disaccharide oligo-
merization) a careful study of optimal glycosyl donor and acceptor
and coupling conditions was carried out. The disaccharide was fi-
nally obtained in high yield and complete b-stereoselectivity. It is
suitable for further manipulations toward the first synthesis of
N-deacetylated-GlcN–containing peptidoglycan fragments that
are interesting molecules for the study of host innate immune sys-
tem evasion mechanism in bacteria. This work is in progress and
will be published elsewhere.
10. Crich, D.; Vinod, A. U. Org. Lett. 2003, 5, 1297–1300.
11. A comprehensive review: Bongat, A. F. G.; Demchenko, A. V. Carbohydr. Res.
2007, 342, 374–406.
12. Gavard, O.; Hersant, Y.; Alais, J.; Duverger, V.; Dilhas, A.; Bascou, A.; Bonnaffé,
D. Eur. J. Org. Chem. 2003, 3603–3620.
13. Boysen, M.; Gemma, E.; Lahmann, M.; Oscarson, S. Chem. Commun. 2005, 3044–
3046.
14. Yan, R. B.; Yang, F.; Wu, Y.; Zhang, L.-H.; Ye, X.-S. Tetrahedron Lett. 2005, 46,
8993–8995.
15. Jensen, H. H.; Nordstrøm, L. U.; Bols, M. J. Am. Chem. Soc. 2004, 126, 9205–9213.
16. (a) Kinzy, W.; Schmidt, R. R. Liebigs Ann. Chem. 1985, 1537–1545; (b) Wang, L.-
X.; Li, C.; Wang, Q.-C.; Hui, Y.-Z. Tetrahedron Lett. 1993, 34, 7763–7766; (c)
Yang, Y.; Li, Y.; Yu, B. J. Am. Chem. Soc. 2009, 131, 12076–12077.
17. Xue, J.; Khaja, S. D.; Locke, R. D.; Matta, K. L. Synlett 2004, 861–865.
18. Compound 17b: [a]
+7 (c 0.6 in CH2Cl2); 1H NMR (400 MHz, CDCl3): d 7.37–
D
7.25 (20H, m, H-Ar), 7.08 (2H, d, Jortho = 8.4 Hz, H-Ar PMB), 6.80 (2H, d,
Jortho = 8.4 Hz, H-Ar PMB), 5.86 (1H, m, OCH2CH@CH2), 5.28 (2H, m, NH, trans
OCH2CH@CHH), 5.22 (1H, br d, Jvic = 10.4 Hz, cis OCH2CH@CHH), 5.08 (1H, t,
J3,2 = J3,4 10.1 Hz, H-3A), 5.06 (1H, d, Jgem = 12.5 Hz, OCHHCCl3), 4.97 (1H, d,
Jgem = 12.5 Hz, OCHHCCl3), 4.93 (1H, dd, J1,2 = 3.5 Hz, H-1A), 4.81 (2H, s,
Acknowledgment
OCH2pOMePh), 4.69–4.60 (4H, m,
4 OCHHPh), 4.51 (1H, d, Jgem = 12.1 Hz,
OCHHPh), 4.47 (2H, s, OCH2Ph), 4.45 (1H, d, Jgem = 10.5 Hz, OCHHPh), 4.21 (1H,
dd, Jgem = 12.5 Hz, Jvic = 5.2 Hz, OCHHCH@CH2), 4.13 (1H, d, J1,2 = 7.2 Hz, H-1B),
4.07–3.91 (5H, m, H-2A, H-4A, H-5A, H-6aA, OCHHCH@CH2), 3.79 (3H, s, OMe),
3.72 (1H, dd, Jgem = 9.8 Hz, J6b,5 = 1.7 Hz, H-6bA), 3.61 (1H, d, Jgem = 10.8 Hz,
J6a,5 = 1.7 Hz, H-6aB), 3.47 (2H, m, H-4B, H-6bB), 3.23 (3H, m, H-2B, H-3B, H-5B);
13C NMR (100 MHz, CDCl3): d 159.3 (Cipso PMB), 155.3, 154.1 (OCOOCH2Ph,
NCOOCH2CCl3), 138.4, 138.0, 137.7, 135.2 (4 Cipso Bn), 133.1 (OCH2CH@CH2),
130.1 (Cipso PMB), 129.4–125.0 (C-Ar), 118.4 (OCH2CH@CH2), 113.8 (C-Ar),
100.8 (C-1B), 96.3 (C-1A), 83.3 (C-3B), 77.6 (C-4B), 75.7 (C-3A), 75.4 (C-5B,
OCH2pOMePh), 74.7 (OCH2Ph), 74.5 (C-4A, OCH2Ph), 73.5 (2 OCH2Ph), 70.3 (C-
5A), 69.5 (OCH2CCl3), 68.7 (C-6B), 68.6 (OCH2CH@CH2), 67.7 (C-6A), 66.4 (C-2B),
55.3 (OMe), 54.1 (C-2A). MALDI TOF-MS: calcd for C55H59Cl3N4O14 (m/z),
1104.31 [M+H]+; found, 1127.07 [M+Na]+. Anal. Calcd for C55H59Cl3N4O14: C,
59.70; H, 5.37; N, 5.06. Found: C, 59.55; H, 5.34; N, 4.99.
NMR and MS facilities of CIMCF (Centro Interdipartimentale di
Metodologie Chimiche Fisiche) are acknowledged.
References and notes
1. Vollmer, W.; Blanot, D.; de Pedro, M. A. FEMS Microbiol. Rev. 2008, 32, 149–167.
2. Vollmer, W. FEMS Microbiol. Rev. 2008, 32, 287–306.
3. Boneca, I. G.; Dussurget, O.; Cabanas, D.; Nahori, M.-A.; Sousa, S.; Lecuit, M.;
Psylinakis, E.; Bouriotis, V.; Hugot, J.-P.; Giovannini, M.; Coyle, A.; Bertin, J.;
Namane, A.; Rousselle, J.-C.; Cayet, N.; Prévost, M.-C.; Balloy, V.; Chignard, M.;
Philpott, D. J.; Cossart, P.; Girardin, S. E. Proc. Natl. Acad. Sci. U.S.A. 2007, 104,
997–1002.
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Lanzetta, R.; Parrilli, M.; Molinaro, A.; Newman, M.-A.; Cooper, R. M. Chem. Biol.
2008, 15, 438–448.
Compound 19: [a]
D +25.0 (c 2.0 in CH2Cl2); 1H NMR (500 MHz, CDCl3): d 7.37–
7.30 (15H, m, H-Ar), 7.07 (2H, d, Jortho = 8.5 Hz, H-Ar PMB), 6.81 (2H, d,
Jortho = 8.5 Hz, H-Ar PMB), 5.86 (1H, m, OCH2CH@CH2), 5.37 (d, 1H, J1,2 = 3.5 Hz,
H-1A), 5.25 (1H, br d, Jvic = 17.0 Hz, trans OCH2CH@CHH), 5.15 (1H, br d,
Jvic = 11.0 Hz, cis OCH2CH@CHH), 4.83 (2H, s, OCH2pOMePh), 4.73 (1H, d,
Jgem = 12.0 Hz, OCHHPh), 4.69 (1H, d, Jgem = 10.5 Hz, OCHHPh), 4.66 (1H, q,
Jvic = 7.5 Hz, CH3CHO), 4.54 (1H, d, Jgem = 11.5 Hz, OCHHPh), 4.50 (1H, d,
Jgem = 10.5 Hz, OCHHPh), 4.46 (1H, d, Jgem = 12.0 Hz, OCHHPh), 4.43 (1H, d,
Jgem = 11.5 Hz, OCHHPh), 4.25 (1H, d, J1,2 = 8.0 Hz, H-1B), 4.22 (2H, m,
OCH2CH3), 4.11 (1H, dd, Jgem = 13.5 Hz, Jvic = 5.5 Hz, OCHHCH@CH2), 4.06 (1H,
t, J4,3 = J4,5 = 10.0 Hz, H-4A), 3.99 (1H, dd, Jgem = 13.5 Hz, Jvic = 5.5 Hz,
OCHHCH@CH2), 3.95 (dd, 1H, J2,3 = 9.0 Hz, J2,1 = 3.5 Hz, H-2A), 3.80–3.64 (m,
10H, H-3A, H-4B, H-5A, H-6aA, H-6bA, H-6aB, H-6bB, OCH3), 3.30 (1H, t,
J2,3 = J2,1 = 8.0 Hz, H-2B), 3.25 (1H, t, J3,4 = J3,2 = 9.5 Hz, H-3B), 3.16 (1H, br d,
J5,4 = 9.6 Hz, H-5B), 2.04 (3H, s, CH3CO), 1.36 (3H, d, Jvic = 7.5 Hz, CH3CHO), 1.30
(3H, t, Jvic = 7.5 Hz, OCH2CH3); 13C NMR (125 MHz, CDCl3): d 176.3 (COOEt),
170.1 (NHCOCH3), 159.3 (Cipso PMB), 137.9–137.7 (3 Cipso Bn), 134.1
(OCH2CH@CH2), 130.2 (Cipso PMB), 129.3–127.6 (C-Ar), 116.9 (OCH2CH@CH2),
113.8 (C-Ar), 100.6 (C-1B), 95.9 (C-1A), 83.3, 77.3, 76.8, 75.4, 75.2, 75.1, 74.5,
74.4, 73.4, 73.1, 70.6, 68.7, 68.3, 67.8, 66.7 (C-2A, C-3A, C-3B, C-4A, C-4B, C-5A, C-
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64, 3381–3391.
5B, C-6A, C-6B, OCHCH3,
3 OCH2Ph, OCH2PhOMe, OCH2CH@CH2), 61.2
(OCH2CH3), 55.2, 54.4 (C-2A, OCH3), 23.1 (CH3CO), 18.5 (CH3CH), 14.1
(OCH2CH3). MALDI TOF-MS: calcd for C51H62N4O13 (m/z), 938.43 [M+H]+;
found, 961.21 [M+Na]. Anal. Calcd for C51H62N4O13: C, 65.23; H, 6.65; N, 5.97.
Found: C, 65.35; H, 6.55; N, 6.01.
7. Saha, S. L.; Van Nieuwenhze, M. S.; Hornback, W. J.; Aikins, J. A.; Blaszczak, L. C.
Org. Lett. 2001, 3, 3575–3577.