A Synthesis of L-Vancosamine Derivatives from Non-Carbohydrate Precursors by a Short Sequence Based on the Marshall, McDonald, and Du Bois Reactions

Article abstract of DOI:10.1021/ol035479p

(Matrix presented). The carbamate-protected L-vancosamine glycal, viewed as a universal precursor for vancosamine derivatives, was prepared by a short scheme based on diastereoselective addition of an allenyl stannane to a lactaldehyde ether, the tungsten

Full text of DOI:10.1021/ol035479p

ORGANIC
LETTERS
2003
Vol. 5, No. 21
3891-3893
A Synthesis of L-Vancosamine
Derivatives from Non-Carbohydrate
Precursors by a Short Sequence Based
on the Marshall, McDonald, and Du Bois
Reactions
Kathlyn A. Parker* and Wonsuk Chang
Department of Chemistry, State UniVersity of New York at Stony Brook,
Stony Brook, New York 11794-3400
kparker@notes.cc.sunysb.edu
Received August 5, 2003
ABSTRACT
The carbamate-protected L-vancosamine glycal, viewed as a universal precursor for vancosamine derivatives, was prepared by a short scheme
based on diastereoselective addition of an allenyl stannane to a lactaldehyde ether, the tungsten-catalyzed alkynol cycloisomerization, and the
rhodium-catalyzed C−H insertion of a carbamate nitrogen. This sequence is a prototype for a new and efficient strategy for the synthesis of
3-amino sugar derivatives. The key intermediate was elaborated to the silyl ether of N,N-dimethyl vancosamine glycal.
L-Vancosamine (1) and N,N-dimethylvancosamine (2) are
constituents of complex antibiotics of diverse structural types.
L-Vancosamine is a functional component of vancomycin,1
the glycopeptide that has attained the status of antibiotic of
last resort against resistant Gram-positive bacteria.2,3 N,N-
Dimethylvancosamine appears as an O-glycoside in the nor-
cardicyclin (anthracycline) antibiotics4 and as a C-glycoside
in the pluramycin (kidamycin) antibiotics.5
“reverse polarity strategy” based on the addition of lithiated
glycals to quinonoid substrates.6 If we are to implement this
approach for members of the pluramycin group of antitumor
antibiotics, we need access to a protected N,N-dimethyl-L-
vancosamine glycal, particularly the silyl ether 3. Although
it would be reasonable to prepare this type of intermediate
from L-vancosamine (which is available from synthesis7 and
from degradation8 of vancomycin), we have been interested
in devising a direct preparation of this and related reagents.
In fact, the racemic vancosamine glycal derivative 4 has
been prepared by McDonald in an 8-step sequence7s based
on a Staudinger cycloaddition and the author’s own alkynol
For the synthesis of aryl C-glycoside antibiotics, we wish
to establish the key aryl C-glycoside connections by a
(1) (a) Grdadolnik, S. G.; Pristovsek, P.; Mierke, D. F. J. Med. Chem.
1998, 41, 2090. (b) Williams, D. H.; Waltho, J. P. Biochem. Pharmacol.
1988, 37, 133.
(2) (a) Williams, D. H.; Bardsley, B. Angew. Chem., Int. Ed. 1999, 38,
1172. (b) Malabarba, A.; Nicas, T. I.; Thompson, R. C. Med. Res. ReV.
1997, 17, 69.
(3) Even vancomycin has encountered resistant organisms. New ana-
logues with a mode of action different from that of vancomycin have been
shown to be effective against resistant strains. See: (a) Walsh, C. Science
1999, 284, 442. (b) Ge, M.; Chen, Z.; Onishi, H. R.; Kohler, J.; Silver, L.
L.; Kerns, R.; Fukuzawa, S.; Thompson, C.; Kahne, D. Science 1999, 284,
507. (c) Ritter, T. K.; Wong, C.-H. Angew. Chem., Int. Ed. 2001, 40, 3508.
(4) An earlier designation for these compounds was as 0624-A and -B;
see: (a) Tanaka, Y.; Mikami, Y.; Yazawa, K. U.S. Patent 5,965,407, 1999.
(b) Tanaka, Y.; Gra¨efe, U.; Yazawa, K.; Mikami, Y. J. Antibiot. 1998, 51,
589. (c) Tanaka, Y.; Gra¨fe, U.; Yazawa, K.; Mikami, Y.; Ritzau, M. J.
Antibiot. 1997, 50, 822.
(5) (a) Furukawa M.; Itai, A.; Iitaka, Y. Tetrahedron Lett. 1973, 13, 1065.
(b) Nadig, H.; Se´quin, U. HelV. Chim. Acta 1987, 70, 1217.
(6) (a) Parker, K. A.; Koh, Y.-H. J. Am. Chem. Soc. 1994, 116, 11149.
(b) Parker, K. A. Pure Appl. Chem. 1994, 66, 2135.
10.1021/ol035479p CCC: $25.00 © 2003 American Chemical Society
Published on Web 09/17/2003

cycloisomerization (McDonald reaction) of alkynol 7. The
preparation of the selectively functionalized 7 would be based
on the diastereoselective addition (Marshall reaction)11,12 of
a (P)-allenyl stannane to an (S)-lactic aldehyde.
The resulting scheme involves the sequential application
of three recently developed reactions, each of which ac-
complishes a previously difficult or impossible transforma-
tion. Implementation of the plan was remarkably facile.
Figure 1. L-Vancosamine (1), N,N-dimethyl-L-vancosamine (2),
silyl-protected N,N-dimethyl-L-vancosamine glycal 3, and protected
L-vancosamine glycal 4.
Scheme 2. Stereoselectivity of the Marshall Reaction
cycloisomerization reaction.9 Although both efficient and
stereoselective, this synthesis did not appear to us to be
readily adaptable to the preparation of chiral glycal deriva-
tives.
In this letter we present a novel strategy for the synthesis
of oxazolidinone 5, which we view as a universal precursor
to vancosamine derivatives. Furthermore, we describe the
conversion of this key compound to the protected N,N-
dimethyl-L-vancosamine glycal 3, intended for use in our
approach to the synthesis of pluramycin antibiotics.
In our retrosynthetic analysis (Scheme 1), we envisaged
oxazolidinone 5 to be available from the stereospecific C-H
Alkynol 10 was obtained by the addition of (P)-allenyl
stannane 813 to (S)-lactic aldehyde benzyl ether 914 according
to the method of Marshall.11 Purification by filtration through
KF-loaded Celite, a procedure described by Roush et al.,15
followed by flash column chromatography provided the
major product, alkynol 10, and a small amount of the
diastereomeric alkynol 11.16 Protecting group modification
was required prior to the cycloisomerization reaction.
Therefore, alkynol 10 was functionalized as the carbamate
12 by treatment with trichloroacetyl isocyanate followed by
methanolysis.17 Then the benzyl group was removed with
DDQ to afford alkynol 7, the substrate for the McDonald
reaction. Irradiation of a solution of alkynol 7 at 350 nm
was carried out in the presence of 10 mol % of W(CO)6 and
excess triethylamine. After low-temperature workup (see
Supporting Information), crystalline glycal 6 was obtained
in 87% yield.
Scheme 1. Oxazolidinone 5, and Its Retrosynthetic Analysis
(8) Dushin, R. G.; Danishefsky, S. J. J. Am. Chem. Soc. 1992, 114, 3471.
(9) McDonald, F. E.; Reddy, K. S.; Diaz, Y. J. Am. Chem. Soc. 2000,
122, 4304.
(10) Espino, C. G.; Du Bois, J. Angew. Chem., Int. Ed. 2001, 40, 598.
(11) (a) Marshall, J. A.; Wang. X. J. J. Org. Chem. 1991, 56, 3211. (b)
Marshall, J. A.; Wang. X. J. J. Org. Chem. 1992, 57, 1242.
(12) For a review of this and related stereoselective addition reactions,
see: Marshall, J. A. Chem. ReV. 1996, 96, 31.
(13) Prepared from commercially available (R)-(+)-3-butyn-2-ol in two
steps by the reported procedure: (a) Marshall, J. A.; Lu, Z.-H.; Johns, B.
A. J. Org. Chem. 1998, 63, 817. (b) Marshall, J. A.; Grant, C. M. J. Org.
Chem. 1999, 64, 8214.
bond insertion reaction (Du Bois reaction)10 of the 3-methyl
3-deoxy glycal 6, which would be accessed through the
(7) Synthesis of vancosamine or its derivatives: (a) Thang, T. T.;
Winternitz, F.; Olesker, A.; Lagrange, A.; Lukacs, G. J. Chem. Soc., Chem.
Commun. 1979, 153. (b) Dyong, I.; Friege, H. Chem. Ber. 1979, 112, 3273.
(c) Thang, T. T.; Winternitz, F.; Olesker, A.; Lagrange, A.; Lukacs, G.
Tetrahedron Lett. 1980, 21, 4495. (d) Ahmad, H. I.; Brimacombe, J. S.;
Mengech, A. S.; Tucker, L. C. N. Carbohydr. Res. 1981, 93, 288. (e) Dyong,
I.; Friege, H.; Luftmann, H.; Merten, H. Chem. Ber. 1981, 114, 2669. (f)
Fronza, G.; Fuganti, C.; Grasselli, P.; Pedrocchi-Fantoni, G. Tetrahedron
Lett. 1981, 22, 5073. (g) Brimacombe, J. S.; Mengech, A. S.; Rahman, K.
M. M.; Tucker, L. C. N. Carbohydr. Res. 1982, 110, 207. (h) Fronza, G.;
Fuganti, C.; Grasselli, P.; Pedrocchi-Fantoni, G. J. Carbohydr. Chem. 1983,
2, 225. (i) Hamada, Y.; Kawai, A.; Shioiri, T. Tetrahedron Lett. 1984, 25,
5413. (j) Hauser, F. M.; Ellenberger, S. R. J. Org. Chem. 1986, 51, 50. (k)
Dyong, I.; Weigand, J.; Thiem, J. Liebigs Ann. Chem. 1986, 577. (l) Klemer,
A.; Wilbers, H. Liebigs Ann. Chem. 1987, 815. (m) Hamada, Y.; Kawai,
A.; Matsui, T.; Hara, O.; Shioiri, T. Tetrahedron 1990, 46, 4823. (n) Greven,
R.; Ju¨tten, P.; Scharf, H.-D. Carbohydr. Res. 1995, 275, 83. (o) Nicolaou,
K. C.; Mitchell, H. J.; van Delft, F. L.; Ru¨bsam, F.; Rodriguez, R. M. Angew.
Chem., Int. Ed. 1998, 37, 1871. (p) Nicolaou, K. C.; Mitchell, J. J.; Jain,
N. F.; Bando, T.; Hughes, R.; Winssinger, N.; Natarajan, S.; Koumbis, A.
E. Chem. Eur. J. 1999, 5, 2648. (q) Nicolaou, K. C.; Baran, P. S.; Zhong,
Y.-L.; Vega, J. A. Angew. Chem., Int. Ed. 2000, 39, 2525. (r) Smith, G. R.;
Giuliano, R. M. Carbohydr. Res. 2000, 323, 208. (s) Cutchins, W. W.;
McDonald, F. E. Org. Lett. 2002, 4, 749.
(14) Prepared in two steps from ethyl (S)-(-)-lactate. O-Benzylation
according to Vaelis and Johnson14a gave ethyl (S)-2-(benzyloxy)propionate
([R]22D -87.0 in CHCl3, c 2.54) with enantiomeric purity >99%, determined
by 1H NMR study with chiral shift reagent, Eu(hfc)3. DIBAL reduction by
the procedure of Solladie´-Cavallo and Bonne14b provided aldehyde 9 ([R]22
D
-61.2 in CHCl3, c 6.68): (a) Varelis, P.; Johnson, B. L. Aust. J. Chem.
1995, 48, 1775. (b) Solladie´-Cavallo, A.; Bonne, F. Tetrahedron: Asymmetry
1996, 7, 171.
(15) Scheidt, K. A.; Bannister, T. D.; Tasaka, A.; Wendt, M. D.; Savall,
B. M.; Fegley, G. J.; Roush, W. R. J. Am. Chem. Soc. 2002, 124, 6981.
1
(16) Alkynol 11 was identified by its H NMR spectrum: Marshall, J.
A.; Chobanian, H. R. J. Org. Chem. 2000, 65, 8357. The reported
enantiomeric excess of commercially available (R)-(+)-3-butyn-2-ol (Aldrich
Chemical Company) was greater than 95%; therefore, a small amount of
the (M)-isomer of the allenyl stannane was presumably involved in the
reaction.
(17) Kocovsky, P. Tetrahedron Lett. 1986, 27, 5521.
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Org. Lett., Vol. 5, No. 21, 2003

target. Reaction of protected glycal 5 with NaH and
Me2SO4 provided N-methyl oxazolidinone 13 in quantitative
yield. Reduction with lithium aluminum hydride provided
crude N,N-dimethyl vancosamine glycal, which was directly
subjected to silylation. Thus, the desired 3 was obtained in
83% yield from the key vancosamine synthon 5. Short
Scheme 3. Completion of the Synthesis of Oxazolidinone 5a
Scheme 4. Preparation of Protected
N,N-Dimethyl-L-vancosamine Glycala
a Reagents and conditions: (a) CCl3C(O)NCO, CH2Cl2; K2CO3/
MeOH. (b) DDQ, CH2Cl2, pH 7 buffer. (c) 10 mol % of W(CO)6,
Et3N, THF, hν, 57 °C. (d) 10 mol % of Rh2(OAc)4, PhI(OAc)2,
MgO, CH2Cl2, 40 °C.
a Reagents and conditions: (a) NaH, Me2SO4, CH2Cl2. (b) LAH,
ether. (c) TBSOTf, 2,6-lutidine, CH2Cl2.
The synthesis of the potentially versatile intermediate,
protected L-vancosamine glycal 5, was completed by the
regio- and stereoselective C-H insertion of the urethane
nitrogen, presumably via the rhodium nitrene18 derived from
urethane 6. A modification of the optimal conditions of Du
Bois et al.10 (10 mol % of Rh2(OAc)4) afforded crystalline
oxazolidinone 5 in high yield. As shown in Figure 2, an
sequences based on the principle demonstrated in this letter
should provide improved and practical preparations of
3-amino glycals, branched and unbranched, in both chiral
series.19,20 As glycals are generally useful precursors to both
O-21 and C-glycosides,6,22 our strategy should find broad
application in the synthesis of a variety of antibiotics that
contain amino sugars. The use of aminoglycal reagents,
including the protected N,N-dimethylvancosamine glycal 3,
in further synthetic transformations will be reported in due
course.
Acknowledgment. This work was supported by the
National Cancer Institute (grant no. CA-87503). K.A.P. and
W.C. are grateful to Professor Joseph W. Lauher of the
Chemistry Department at Stony Brook for the X-ray crystal-
lographic study of oxazolidinone 5. They also thank Dr. Tun-
Li Shen (Brown University) for mass spectroscopic data.
Supporting Information Available: Experimental details
and full characterization for all new compounds; X-ray
crystallographic data of 5 in CIF format. This material is
available free of charge via the Internet at http://pubs.acs.org.
Figure 2. The X-ray crystal structure of oxazolidinone 5.
OL035479P
(19) For a recent review on the approaches to synthesis of deoxy sugars,
see: Kirschning, A.; Jesberger, M.; Scho¨ning, K.-U. Synthesis 2001, 507.
(20) For reviews of the syntheses of 3-amino-2,3,6-trideoxyhexoses,
see: (a) Hauser, F. M.; Ellenberger, S. R. Chem. ReV. 1986, 86, 35. (b)
Pelya´s, I. F.; Monneret, C.; Herczegh, P. Synthetic Aspects of Aminodeoxy
Sugars of Antibiotics; Springer-Verlag: Berlin, Germany, 1988.
(21) For recent examples, see: (a) McDonald, F. E.; Wu, M. Org. Lett.
2002, 4, 3979. (b) Yadav, J. S.; Reddy, B. V. S.; Reddy, K. B.;
Satyanarayana, M. Tetrahedron Lett. 2002, 43, 7009. (c) Pachamuthu, K.;
Vankar, Y. D. J. Org. Chem. 2001, 66, 7511. (d) Toshima, K.; Nagai, H.;
Ushiki, Y.; Matsumura, S. Synlett 1998, 1007.
X-ray crystal structure confirmed the relative stereochemistry
of the three chiral centers in 5 and corroborated the structure
of alkynol 10 as well. Thus, the useful L-vancosamine glycal
equivalent 5 is available in 44% overall yield based on ethyl
(S)-(-)-lactate in seven steps.
Our interests directed us to pursue the preparation of
protected N,N-dimethyl-L-vancosamine glycal 3 as our next
(22) For example, see: (a) Prandi, J.; Beau, J.-M. Tetrahedron Lett. 1989,
30, 4517. (b) Brown, D. S.; Bruno, M.; Davenport, R. J.; Ley, S. V.
Tetrahedron 1989, 45, 4293. (c) Lesimple, P.; Beau, J.-M.; Sinay, P.
Carbohydr. Res. 1987, 171, 289.
(18) (a) Breslow, R.; Gellman, S. H. J. Am. Chem. Soc. 1983, 105, 6728.
(b) Nageli, I.; Baud, C.; Bernardinelli, G.; Jacquier, Y.; Moran, M.; Muller,
P. HelV. Chim. Acta 1997, 80, 1087.
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