ORGANIC
LETTERS
2002
Vol. 4, No. 8
1359-1361
Stereoselective Synthesis of
myo-Inositol via Ring-Closing
Metathesis: A Building Block for
Glycosylphosphatidylinositol (GPI)
Anchor Synthesis
Rosemary M. Conrad, Michael J. Grogan, and Carolyn R. Bertozzi*
Departments of Chemistry and Molecular and Cell Biology, Center for New Directions
in Organic Synthesis,† and Howard Hughes Medical Institute, UniVersity of California,
Berkeley, California 94720
Received February 6, 2002
ABSTRACT
Here we report a concise stereoselective synthesis of myo-inositol via ring-closing metathesis. A readily available bis-Weinreb amide of
D-tartrate served as a key intermediate.
The glycosylphosphatidylinositol (GPI) anchor is a post-
translational modification that covalently links certain pro-
teins to the outer leaflet of eukaryotic cell membranes (Figure
1). The phosphatidylinositol moiety is a unique feature of
the GPI anchor’s glycan and may be involved in clustering
of GPI-anchored proteins on the cell surface.1 GPI anchors
are also prevalent in parasitic organisms such as Trypano-
soma brucei and are major immunogenic determinants that
are recognized by antigen presentation molecules in mam-
malian hosts.2 Thus, GPI anchors and analogues thereof may
serve as vaccine components.
Synthetic derivatives of GPI have proven to be critical
tools for probing the biosynthesis, structure, and im-
munological properties of GPI anchors. Total syntheses of
the anchor have been reported,4 and a central theme that has
emerged from these efforts is the difficulty in preparing a
selectively protected myo-inositol building block. myo-
Inositol or its 1,2-anhydro analogue, conduritol B, can be
† The Center for New Directions in Organic Synthesis is supported by
Bristol-Myers Squibb as a Sponsoring Member.
(2) (a) Schofield, L.; McConville, M. J.; Hansen, D.; Campbell, A. S.;
Fraser-Reid, B.; Grusby, M. J.; Tachado, S. D. Science 1999, 283, 225-
229. Reviewed in: (b) McConville, M. J.; Menon, A. K. Mol. Membrane
Biol. 2000, 17, 1-16. (c) Ferguson, M. A. J. J. Cell Sci. 1999, 112, 2799-
2809.
(3) McConville, M. J.; Ferguson, M. A. J. Biochem. J. 1993, 294, 305-
324.
(4) (a) Reviewed in: Gigg, R.; Gigg, J. In Glycopeptides and Related
Compounds; Large, D. G., Warren, C. D., Eds.; Marcel Dekker: New York,
1997; pp 327-392. (b) Baeschlin, D. K.; Chaperon, A. R.; Charbonneau,
V.; Green, L. G.; Ley, S. V.; Lucking, U.; Walther, E. Angew. Chem., Int.
Ed. 1998, 37, 3423-3428. (c) Campbell, A. S.; Fraser-Reid, B. J. Am. Chem.
Soc. 1995, 117, 10387-10388. (d) Udodong, U. E.; Madsen, R.; Roberts,
C.; Fraser-Reid, B. J. Am. Chem. Soc. 1993, 115, 7886-7887.
(1) (a) Benting, J.; Rietveld, A.; Ansorge, I.; Simons, K. FEBS Lett. 1999,
462, 47-50. (b) Denny, P. W.; Field, M. C.; Smith, D. F. FEBS Lett. 2001,
491, 148-153. (c) Hanada, K.; Nishijima, M.; Akamatsu, Y.; Pagano, R.
E. J. Biol. Chem. 1995, 270, 6254-6260. (d) Harder, T.; Scheiffele, P.;
Verkade, P.; Simons, K. J. Cell Biol. 1998, 141, 929-942. (e) Ilangumaran,
S.; He, H. T.; Hoessli, D. C. Immunol. Today 2000, 21, 2-7. (f) Kasahara,
K.; Sanai, Y. Biophys. Chem. 1999, 82, 121-127. (g) Kenworthy, A. K.;
Petranova, N.; Edidin, M. Mol. Biol. Cell 2000, 11, 1645-1655. (h)
Schroeder, R. J.; Ahmed, S. N.; Zhu, Y.; London, E.; Brown, D. A. J.
Biol. Chem. 1998, 273, 1150-1157. (i) Simons, K.; Ikonen, E. Nature 1997,
387, 569-572. (j) Zhang, F.; Schmidt, W. G.; Hou, Y.; Williams, A. F.;
Jacobson, K. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 5231-5235.
10.1021/ol025680k CCC: $22.00 © 2002 American Chemical Society
Published on Web 03/23/2002