Total synthesis of desferrisalmycin B

Article abstract of DOI:10.1021/ja028386w

The first total synthesis of a naturally occurring siderophore antibiotic, desferrisalmycin B, is described, and the configuration of the unknown stereocenter is assigned. The synthesis features a synthetic strategy of constructing the novel amino-heptopyranoside component by stereoselective dihydroxylation followed by a Bose-modified Mitsunobu reaction. Through this convergent approach, other members of salmycins should also be synthetically accessible.

Full text of DOI:10.1021/ja028386w

Published on Web 11/20/2002
Total Synthesis of Desferrisalmycin B
Li Dong, John M. Roosenberg II, and Marvin J. Miller*
Contribution from the Department of Chemistry and Biochemistry, UniVersity of Notre Dame,
251 Nieuwland Science Hall, Notre Dame, Indiana 46556-5670
Received September 3, 2002
Abstract: The first total synthesis of a naturally occurring siderophore antibiotic, desferrisalmycin B, is
described, and the configuration of the unknown stereocenter is assigned. The synthesis features a synthetic
strategy of constructing the novel amino-heptopyranoside component by stereoselective dihydroxylation
followed by a Bose-modified Mitsunobu reaction. Through this convergent approach, other members of
salmycins should also be synthetically accessible.
Introduction
Siderophores are functionally defined as low molecular mass
molecules which acquire iron(III) from the environment and
transport it into microorganisms.1 Because of the significant
roles they play in the active transport of physiologically essential
iron(III) through microbe cell membranes, it is not surprising
that siderophore-drug conjugates are attracting more and more
attention from both medicinal chemists and clinical researchers
as novel drug delivery systems in the war against microbial
infections, especially in an era of widespread emergence of
multidrug-resistant (MDR) strains.2 There have been three
families of compounds identified as natural siderophore-drug
conjugates, including ferrimycin, albomycin, and salmycin.3
Among these, salmycin B (1b, Figure 1) was isolated from the
fermentation broth of Streptomyces Violaceus DSM 8286 in
1995 by Ve´rtesy and co-workers.3c Salmycin B, along with
other congeners (A, C, and D, 1a, 1c, and 1d, respectively,
Figure 1), shows potent antibacterial activity against both
Staphylococci and Streptococci, including resistant strains of
these pathogens.3c
The structure of salmycin B incorporates the known sidero-
phore, danoxamine,4 and an unusual amino-disaccharide, which
contains a D-arabino-hexopyranos-2-ulose and a 6-deoxy-6-
(methylamino)-D-gluco-heptopyranose. The unique and complex
architecture of this compound, in conjunction with its potential
therapeutic significance, stimulated our synthesis of desferri-
Figure 1. Salmycin and retrosynthetic analysis.
salmycin B. Although most of the stereochemical information
for this compound has been revealed on the basis of extensive
NMR spectroscopic experiments and degradation studies, the
stereochemistry of C-6′′ at the heptopyranose remained
unknown.3c Thus, the syntheses of both stereoisomers of
desferrisalmycin B also provided an opportunity to unambigu-
ously assign this configuration.
* To whom correspondence should be addressed. E-mail: mmiller1@
nd.edu.
(1) (a) Neilands, J. B. J. Biol. Chem. 1995, 270, 26723. (b) Matzanke, B. F.;
Muller-Matzanke, G.; Raymond, K. N. In Iron Carriers and Iron Proteins;
Loehr, T. M., Ed.; VCH: New York, 1989; Chapter 1.
(2) (a) Miller, M. J.; Malouin, F. Acc. Chem. Res. 1993, 26, 241. (b)
Roosenberg, J. M., II; Lin, Y.-M.; Lu, Y.; Miller, M. J. Curr. Med. Chem.
2000, 9, 159. (c) Braun, V.; Braun, M. Curr. Opin. Microbiol. 2002, 5,
194.
(3) (a) Benz, G.; Schro¨der, T.; Kurz, J.; Wu¨nsche, C.; Karl, W.; Steffens, G.;
Pfitzner, J.; Schmidt, D. Angew. Chem., Int. Ed. Engl. 1982, 21, 527. (b)
Bickel, H.; Gauman, E.; Nussberger, G.; Reusser, P.; Vischer, E.; Vosser,
W.; Wettstein, A.; Azhner, H. HelV. Chim. Acta 1960, 43, 2105. (c) Ve´rtesy,
L.; Aretz, W.; Fehlhaber, H.-W.; Koger, H. HelV. Chim. Acta 1995, 78,
46.
Results and Discussion
The conspicuous structural features of salmycin B led us to
a retrosynthetic analysis disconnecting this compound into three
major parts as shown in Figure 1. The protected siderophore
(4) Huber, P.; Leuenberger, H.; Keller-Schierlein, W.-K. HelV. Chim. Acta 1986,
69, 231.
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J. AM. CHEM. SOC. 2002, 124, 15001-15005
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A R T I C L E S
Dong et al.
Scheme 1 a
Scheme 2 a
a Reagents and conditions: (a) (i) Ac2O, I2, rt; (ii) HBr/AcOH, CH2Cl2,
rt; (b) CH3OH, 2,6-lutidine, rt; (c) K2CO3, CH3OH, rt; (d) (i) TBSCl,
imidazole, DMF, rt; BnBr, NaH, DMF, rt, 67% for six steps; (e) (i) Dowex
resin (50 × 8-400), 95% EtOH, rt; (ii) CCl3CN, DBU, CH2Cl2, rt, 60% for
two steps.
component 2 (n ) 5) has been synthesized in this group.5 We
envisioned that hexapyranoside 3 and heptopyranoside 4 could
be conjoined through a stereoselective trichloroacetimidate
glycosidation.6 Hexapyranose 3 was readily prepared through
the following sequence (Scheme 1). Starting from D-mannose,
peracetylation, anomeric bromination, and cyclization gave rise
to ortho ester 6,7,8 which was deacetylated to generate compound
7. The primary hydroxyl group of triol 7 was selectively
protected as a tert-butyldimethylsilyl (TBS) ether followed by
benzyl protection of the remaining hydroxyl groups to furnish
suitably protected ortho ester 8. Thus, by modifying the
procedure described by Ley et al.,9 multigram quantities of
compound 8 could be easily accessed from D-mannose without
purification of the intermediates. The ortho ester was then
hydrolyzed upon exposure to Dowex resin (50 × 8-400) without
jeopardizing the acid-sensitive TBS group.10 Treatment of the
resulting crude material with CCl3CN and DBU finalized the
preparation of trichloroacetimidate 3.11
a Reagents and conditions: (a) Bu2SnO, Tol/CH3OH, reflux; TsCl, TEA,
Tol, rt, 89%; (b) BnBr, Ba(OH)2, BaO, DMF, rt, 88%; (c) NaBH4, DMSO,
140 °C, 82%; (d) PMBCl, TBAB, NaH, DMF, rt, 94%; (e) BH3‚THF,
Bu2BOTf, 0 °C, 88%; (f) (CO)2Cl2, DMSO, CH2Cl2, -78 °C; NEt3 -78
°C to rt.
mask the 2-hydroxyl group.13 Benzylation of the remaining
alcohol proceeded uneventfully to provide compound 11. In the
following step, discharge of the tosyl group in compound 11
by NaBH4 reduction at elevated temperature regenerated the
2-hydroxyl group.14 This transformation was sensitive to the
concentration of the reaction, and diluted conditions were critical
for achieving a reproducibly high yield. Subsequent PMB-
protection of alcohol 12 was followed by the opening of the
benzylidene ring through a Lewis acid-promoted regioselective
borane reduction to expose the C-6 hydroxyl group with
concomitant protection of the C-4 hydroxyl group.15 Swern
oxidation of primary alcohol 14 then successfully generated
aldehyde 15 which was not purified due to the instability of
this compound.16
Having developed a viable route for the preparation of
hexapyranose unit 3, we then attended to the synthesis of the
properly protected heptopyranoside 4. Our synthetic plan called
for the assembly of aldehyde 15, which would serve as a
platform for incorporation of the required additional carbon atom
and introducing an amino group at C-6 through one of several
possible approaches. To access this key intermediate, we took
advantage of the stannylene-mediated regioselective protection
to differentiate the 2,3-hydroxyl of benzyl R-glucoside derivative
9 as depicted in Scheme 2. Multigram quantities of benzylidene
9 can be readily prepared in high enantiomeric purity from
D-glucose by modifying Ogawa’s procedure.12 After the forma-
tion of a 2,3-stannylene intermediate of compound 9 (not
isolated), a tosyl group was selectively introduced to temporarily
With aldehyde 15 in hand, several strategies including a
Strecker reaction,17 the formation of an aziridine,18 aminohy-
(12) (a) Ogawa, T.; Kaburagi, T. Carbohydr. Res. 1982, 103, 53. (b) Ho, W.
H.; Wong, H. N. C.; Laurence, N.; Destrade, C.; Nguyen, H. T.; Noel, I.
Tetrahedron 1995, 51, 7373.
(13) Grindley, T. B.; Thangarasa, R. Can. J. Chem. 1990, 68, 1007. Although
the regioselective benzyl protection of 2-hydroxyl of compound 9 was
reported in ref 12a, under similar conditions, PMB-protection led to a
roughly 1:1 mixture of the two possible isomers. The 2-hydroxyl group of
compound 9 can also be selectively acetylated. However, the following
benzylation led to a complex mixture due to the acetyl migration.
(14) Pozsay, V.; Dubois, E. P.; Pannell, L. J. Org. Chem. 1997, 62, 2832.
(15) Jiang, L.; Chan, T. Tetrahedron Lett. 1998, 39, 355.
(16) Leeuwenburgh, M. A.; Kalker, C.; Duynstee, H. I.; Overkleeft, H. S.; van
der Marcel, G. A.; van Boom, J. H. Tetrahedron 1999, 55, 8253.
(17) (a) Czernecki, S.; Valery, J.-M. Carbohydr. Res. 1988, 184, 121. (b) Arndt,
H.; Polborn, K.; Koert, U. Tetrahedron Lett. 1997, 38, 3879. (c) Brown,
H. C.; Garg, C. P. J. Am. Chem. Soc. 1964, 86, 1085. After the Strecker
reaction of aldehyde 15 with KCN/CH3NH2 hydrochloride and the
subsequent protection of the amino group with a Boc group, the nitrile
could not be reduced to the corresponding aldehyde under various
conditions.
(5) Roosenberg, J. M., II; Miller, M. J. J. Org. Chem. 2000, 65, 4833.
(6) Schmidt, R. R.; Jung, K.-H. Prep. Carbohydr. Chemistry 1996, 283.
(7) Katha, K. P. R.; Field, R. A. Tetrahedron 1997, 53, 11753.
(8) Meldal, M.; Franzyk, H.; Paulsen, H.; Brock, K. J. Chem. Soc., Perkin
Trans. 1 1995, 22, 2883.
(9) Baeschlin, D. K.; Green, L. G.; Hahn, M. G.; Hinzen, B.; Ince, S. J.; Ley,
S. V. Tetrahedron: Asymmetry 2000, 11, 173.
(10) Liu, C. M.; Waren, C. D.; Jeanloz, R. W. Carbohydr. Res. 1985, 136, 273.
(11) Lubineau, A.; Bonnaffe´, D. Eur. J. Org. Chem. 1999, 2523.
(18) (a) Hashimoto, H.; Asano, K.; Fujii, F.; Yoshimura, J. Carbohydr. Res.
1982, 104, 87. (b) Effenberger, F.; Stelzer, U. Tetrahedron: Asymmetry
1995, 6, 283. The aziridine was prepared in less than 10% yield from the
cyanohydrin of aldehyde 15 due to the reductive cleavage of the mesylate
by LAH. The Lewis acid-mediated aziridine opening by benzyl alcohol
also failed.
9
15002 J. AM. CHEM. SOC. VOL. 124, NO. 50, 2002

Total Synthesis of Desferrisalmycin B
A R T I C L E S
Scheme 3 a
furnished diol 17 as an inseparable 5:1 mixture of two
diastereomers.21 The attempts to enhance this stereochemical
bias by using a stoichiometric amount of osmium reagent or an
asymmetric method (AD-mix-R)22 provided little improvement.
However, decreasing the reaction temperature to 0 °C improved
the ratio to 8:1. These selectivities fall into the normal range
observed with monosubstituted allylic alcohols and derivatives.23
Stannylene-mediated regioselective protection of compound 17
successfully installed a benzyl group on the primary hydroxyl
group.24 We were glad to note that the major diastereomer could
be separated at this stage by column chromatography to deliver
compound 18 in an enantiomerically pure form. As the minor
isomer could not be cleanly separated and both epimers were
desirable, compound epi-18 was prepared by inverting the
stereochemistry of the C-6 of compound 18 through a Mitsunobu
reaction followed by removal of the p-nitrobenzoate.25 Both of
these epimers were carried out through the rest of the reaction
sequence separately.
To establish the absolute stereochemistry at C-6 in compound
18, correlation studies were conducted. Hydrogenolysis of
compound 18 removed the PMB and benzyl groups to afford
the corresponding heptose. This product was found to possess
the same optical rotation and melting point as D-glycero-D-gluco-
heptose.26 Thus, the configuration of the new stereogenic center
was unambiguously assigned as R. The anti-selectivity of the
osmylation (with respect to the pyranose ring-oxygen atom) was
in good agreement with Kishi’s empirical rule for predicting
the stereoselectivity of the dihydroxylation of allylic alcohols
and derivatives.27
To install the required methylamino group at C-6, the
mesylate of alcohol 18 was prepared and subjected to a
nucleophilic substitution by methylamine. However, the corre-
sponding mesylate was unreactive toward methylamine. Gratify-
ingly, azide was able to be successfully introduced as an amino
group equivalent through a Bose-modified Mitsunobu reaction,
and the desired compound 19 was obtained in good yield.28
Subsequent reduction of the azido group followed by Cbz
protection then furnished compound 20.29 Finally, N-methylation
and PMB deprotection completed the assembly of heptopyra-
noside 22 (Scheme 3).
a Reagents and conditions: (a) Swern oxidation; CH3PPh3Br, NaHMDS,
THF, 0 °C to rt, 80% for two steps; (b) OsO4, NMO, acetone/H2O, 0 °C to
rt, 92%; (c) Bu2SnO, Tol/MeOH, reflux; BnBr, Tol, 85 °C, 81%; (d) DEAD,
Ph3P, p-nitrobenzoic acid, THF, rt, 89%; (e) K2CO3, MeOH, rt, 96%; (f)
DEAD, PPh3, DPPA, THF, 0 °C to rt, 89%; (g) (i) Ph3P, H2O/THF, reflux;
(ii) CbzCl, TEA, CH2Cl2, 0 °C to rt, 65% for two steps; (h) CH3I, NaH,
DMF, rt, 94%; (i) DDQ, CH2Cl2/H2O, rt, 90%.
droxylation of related olefin 16,19 and addition of organometallic
phenyldimethylsilylmethyl reagents20 were attempted to achieve
the required one-carbon atom chain extension and install the
methyl amino functionality at C-6. However, for various reasons,
none of the above approaches proved feasible with our
substrates. The ultimate solution to this problem relied on the
dihydroxylation of olefin 16 followed by introduction of an
amino group at C-6 (Scheme 3). Toward this end, a consecutive
Swern oxidation and Wittig olefination were conducted on
compound 14 to afford olefin 16 in high yield.16 Treatment of
olefin 16 with OsO4 (5 mol %) and NMO at room temperature
The stage was now set for the stereoselective glycosidation
between components 3 and 22. The TMSOTf-mediated glyco-
sidic bond formation proceeded smoothly to provide disaccha-
ride 23 in excellent yield (Scheme 4). The R-configuration of
the new bond was unambiguously proven by C-H coupling
constants from NMR analyses.30 After the removal of the acetyl
(21) MacManus, D. A.; Grabowska, U.; Biggadike, K.; Bird, M. I.; Davies, S.;
Vulfson, E. N.; Gallagher, T. J. Chem. Soc., Perkin Trans. 1 1999, 295.
(22) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. ReV. 1994,
94, 2483.
(19) (a) Li, G.; Angert, H. H.; Sharpless, K. B. Angew. Chem., Int. Ed. Engl.
1996, 35, 2813. (b) Tao, B.; Schlingloff, T. B.; Sharpless, K. B. Tetrahedron
Lett. 1998, 39, 2507. Both the conversion (∼30%) and the regioselectivity
(1:1.6) of the aminohydroxylation reaction were poor. An extensive assay
of the available ligands showed that they had little effect on the distribution
of regioisomers, while in the absence of any ligand the reaction was very
sluggish. The best result was obtained by employing (DHQ)2AQN as the
ligand which provided a mixture in a ratio of 1.6 to 1 favoring the desired
product.
(20) (a) van Delft, F.; de Kort, M.; van der Marel, G. A.; van Boom, J. H.
Tetrahedron: Asymmetry 1994, 5, 2261. (b) Matsumoto, T.; Kobayashi,
Y.; Takemoto, Y.; Ito, Y.; Kamijo, T.; Harada, H.; Terashima, S. Tetra-
hedron Lett. 1990, 31, 4175. The addition of organometallic phenyldi-
methylsilylmethyl reagents (magnesium or cerium) to aldehyde 15 or
aldimine prepared from 15 and methylamine failed to generate the desired
products.
(23) Cha, J. K.; Kim, N.-S. Chem. ReV. 1995, 95, 1761.
(24) Castro-Palomino, A.; Tsvetkov, Y. E.; Schmidt, R. R. J. Am. Chem. Soc.
1998, 120, 5438.
(25) Ghosh, A. K.; Lei, H. J. Org. Chem. 2000, 65, 4779.
(26) (a) Brimacombe, J. S.; Kabir, N.; Abul, K. M. S. Carbohydr. Res. 1986,
150, 35. L,D-isomer: mp 195-196 °C, [R]D ) +52.0° (c 1.9, H2O). (b)
Begbie, R.; Richtmyer, N. K. Carbohydr. Res. 1966, 2, 272. D,D-isomer:
mp 156-157 °C, [R]D ) +46.2° (c 2.4, H2O). The synthetic sample: mp
154-155 °C, [R]D ) +46.9° (c 0.8, H2O).
(27) (a) Cha, J. K.; Christ, W. J.; Kishi, Y. Tetrahedron Lett. 1983, 24, 3943.
(b) Christ, W. J.; Cha, J. K.; Kishi, Y. Tetrahedron Lett. 1983, 24, 3947.
(c) Cha, J. K.; Christ, W. J.; Kishi, Y. Tetrahedron 1984, 40, 2247.
(28) Lal, B.; Pramanik, B. N.; Manhas, M. S.; Bose, A. K. Tetrahedron Lett.
1977, 19, 1977.
(29) Gololobov, Y. G.; Zhmurova, I. N.; Kasukhin, L. F. Tetrahedron 1981,
37, 437.
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A R T I C L E S
Dong et al.
Scheme 4 a
a Reagents and conditions: (a) 22 (epi-22), TMSOTf, CH2Cl2, 0 °C to rt, 88%; (b) K2CO3, MeOH, rt, 94%; (c) (CO)2Cl2, DMSO, CH2Cl2; TEA, -78
°C to rt, 91%; (d) 80% aqueous AcOH, rt, 83%; (e) SA, DMAP, Py, 80 °C.
Scheme 5 a
a Reagents and conditions: (a) PMBCl, NaH, DMF, rt, 54%; (b) 80% aqueous AcOH, rt, 86%; (c) SA, Py, DMAP 80 °C to rt, 88%; (d) DDQ, CH2Cl2/
H2O, rt, 74%; (e) 28, EDC, HOAt, DMF, 0 °C to rt, 91%; (f) (CO)2Cl2, DMSO, CH2Cl2; TEA, -78 °C to rt, 98%; (g) H2, Pd black, HClO4, rt, 35%.
group from disaccharide 23, a Swern oxidation was performed
to generate ketone 25 that exists as a mixture of the ketone and
the corresponding hydrate. Although compound 26 was obtained
by the cleavage of the TBS group from 25, it was found that
the union of compound 26 and protected danoxamine 25 could
not be accomplished. Various methods including Mitsunobu
reactions,31 DCC/DMAP coupling reactions,32 and Mukaiyama’s
reagent33 all failed to effect the formation of the desired ester
bond.
(30) In mannose, the R-anomers usually give a C-H coupling constant of greater
than 170 Hz, whereas the â-anomers usually give C-H couplings of less
than 160 Hz. The nondecoupled 13C NMR of compound 23 indicated that
the newly formed resonance was at 94.48 ppm with a coupling constant of
170.35 Hz.
(31) McKee, J. A. Ph.D. Thesis, University of Notre Dame, 1991.
(32) Kim, H.; Kim, I. J.; Danishefsky, S. J. J. Am. Chem. Soc. 2001, 123, 35.
(33) Tennant-Eyles, R. J.; Fairbanks, A. J. Tetrahedron: Asymmetry 1999, 10,
391.
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Total Synthesis of Desferrisalmycin B
A R T I C L E S
Finally, we decided to switch the roles of two coupling part-
ners by acylating the disaccharide with succinic anhydride (SA)
and connecting the resulting carboxylic acid to danoxamine
precursor 285 to circumvent the problematic esterification step.
However, our attempts to prepare compound 27 were not suc-
cessful possibly due to the presence of the hydrated ketone.34
After further consideration, we decided to postpone the
oxidation until after the coupling reaction with the siderophore.
Because the eventual removal of the acetyl group in compound
23 was not compatible with the danoxamine-disaccharide ester
linkage35 and the selective acylation of the primary alcohol in
the presence of a secondary hydroxyl group by succinic
anhydride could not be implemented, the 2′-hydroxyl group was
protected as a PMB ether to provide compound 29 (Scheme 5).
Surprisingly, this seemingly straightforward transformation only
proceeded with modest efficiency due to the complication of a
facile silyl group migration under reaction conditions. With
compound 29 in hand, the silyl group was removed by treatment
with aqueous acetic acid, which was followed by acylation with
succinic anhydride and PMB deprotection to afford acid 32.36
Although we did not expect the secondary alcohol to interfere
with the hydroxamate formation, we were pleased to find that
acid 32 turned out to be an ideal coupling partner with com-
pound 28, and conjugate 33 was obtained in excellent yield.
The following Swern oxidation also progressed extremely well
to afford compound 34. The endgame global deprotection by
hydrogenolysis, however, was not trivial. Most of the common
methods led to incomplete conversion or decomposition. After
an extensive investigation of different catalysts and conditions,
we finally discovered that a combination of Pd black and
catalytic perchloric acid was the reagent of choice to effect this
transformation. By employing these conditions, we obtained
compound 35 whose structure was supported by NMR (1H and
13C), IR, and MS analyses (Scheme 5). In a similar fashion,
epi-35 was prepared from compound epi-18.
Through comparison of the NMR spectra of the authentic
sample3c with those of our synthetic material, compound epi-
35 was identified as the natural desferrisalmycin B. On the basis
of these facts, the heptopyranose component of salmycin B has
a D-glycero-D-gluco configuration.
Conclusion
The first total synthesis of desferrisalmycin B was ac-
complished. The synthesis provided a platform from which the
easy entry to other compounds in this family could be achieved.
By preparation of both epimers of desferrisalmycin B and
subsequent comparison with the authentic sample, the stereo-
chemistry of the unknown chiral center was determined. Our
work in this area will significantly advance the understanding
of the siderophore drug delivery systems and facilitate the design
of more effective siderophore-drug conjugates in the future.
Acknowledgment. This research was supported by a grant
from the NIH (AI 30988). L.D. thanks the Reilly and Albany
Molecular fellowships. The authors are grateful to Donald R.
Schifferl and Dr. Jaroslav Zajicek for assistance with NMR
experiments and Dr. William C. Boggess Jr. and Nonka Sevova
for performing MS analyses. We extend our gratitude to Ms.
Maureen Metcalf for her help in the preparation of this
manuscript. We gratefully acknowledge Dr. La´szlo´ Ve´rtesy at
Aventis Pharma Deutschland GmbH for providing copies of
NMR spectra of authentic desferrisalmycin B.
Supporting Information Available: Detailed experimental
procedures and characterization data for compounds 3, 8, 9, and
all new compounds as well as 1H NMR of the authentic sample
(PDF). This material is available free of charge via the Internet
at http://pubs.acs.org.
(34) Bessodes, M.; Dubertret, C.; Jasin, G.; Scherman, D. Bioorg. Med. Chem.
Lett. 2000, 10, 1393. Alternatively, the E-oxime was prepared as a protected
carbonyl compound (Barili, P. L.; Berti, G.; D’Andrea, F.; Di Bussolo, V.
Carbohydr. Res. 1996, 290, 17). This also provided an easy entry to
salmycin A. Unfortunately, although the silyl ether deprotection and
acylation could be conducted without incident to afford the desired acid,
the final coupling reaction with compound 28 failed to afford the desired
product.
JA028386W
(35) The siderophore conjugate was prepared with the 2′-hydroxyl group
protected with an acetyl group. However, deacetylation caused the
simultaneous cleavage of the ester linkage.
(36) Although the coupling reaction of acid 31 and compound 28 afforded the
desired conjugate, this compound was too sensitive to survive the DDQ-
mediated PMB deprotection.
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