ORGANIC
LETTERS
2001
Vol. 3, No. 9
1355-1358
A New Convergent Route to
Aldohexoses from a Common Chiral
Building Block
Masatoshi Honzumi, Takahiko Taniguchi, and Kunio Ogasawara*
Pharmaceutical Institute, Tohoku UniVersity, Aobayama, Sendai 980-8578, Japan
Received February 20, 2001
ABSTRACT
A diastereocontrolled route to the eight aldohexoses has been developed starting from a common cyclohexanoid chiral building block.
Although a number of syntheses of aldohexoses have been
reported, there are so far two methods that are capable of
producing all of the eight possible diastereomers in enantio-
and diastereocontrolled manner. Of these, one by the
Masamune and the Sharpless groups1 employed a reagent-
controlled method using the Katsuki-Sharpless asymmetric
epoxidation reaction2 as the key step, while the other by our
group employed a substrate-controlled method starting from
a common chiral building block having a dioxabicyclo[3.2.1]-
octane framework.3 The previous work from our group has
shown that the chiral building block, obtained by either a
chemical3 or an enzymatic method,4 allowed diastereoselec-
tive introduction of the requisite functionalities on the basis
of the molecular bias of the chiral block, which exerted
inherent convex-face selectivity. We report here an alterna-
tive substrate-controlled synthesis leading to all of the eight
aldohexoses starting from a common cyclohexanoid chiral
building block 1 exerting inherent convex-face selectivity.
The acetate 1 was prepared in both enantiomeric forms either
by an enzymatic5 or a chemical procedure6 so as to serve as
a chiral equivalent of cis-1,4-dihydroxycyclohexane-2,5-
diene, and it actually allowed diastereocontrolled construction
of a variety of natural products on the basis of its molecular
bias and a masked cyclohexene double bond.7 The present
study using (+)-1 demonstrates the synthesis of four each
of the L- and D-diastereomers of aldohexoses via the four
conduritol derivatives 3-6 generated through the common
bromo-ether intermediate,8,9 (+)-2 (Scheme 1).
Thus, (+)-1 was first transformed into bromo-ether9 2 to
block double bond and hydroxy functionalities on sequential
O-protection, deacetylation, and exposure to NBS. Catalytic
dihydroxylation of 2 occurred from the convex face to give
dibenzyl ether 7, mp 91-92 °C, [R]29D -63.1 (c 1.3, CHCl3),
after benzylation. The double bond blocked was regenerated
at this point to give alcohol 8, [R]29D +36.0 (c 1.2, CHCl3),
on reflux of 7 with zinc in methanolic acetic acid. Ther-
molysis of 8 in refluxing diphenyl ether followed by
benzylation afforded 9, [R]31 +32.2 (c 1.1, CHCl3).
(1) (a) Ko, S. Y.; Lee, A. W. M.; Masamune, S.; Leed, L. A., III;
Sharpless, K. B.; Walker, F. J. Science 1983, 220, 949. (b) Ko, S. Y.; Lee,
A. W. M.; Masamune, S.; Leed, L. A., III; Sharpless, K. B.; Walker, F. J.
Tetrahedron 1990, 46, 245.
(2) Johnson, R. A.; Sharpless, K. B. ComprehensiVe Organic Synthesis;
Trost, B. M., Fleming, I, Eds.; Pergamon: Oxford, 1991; Vol. 7, pp 389-
436.
(3) (a) Takeuchi, M.; Taniguchi, T.; Ogasawara, K. Synthesis 1999, 341.
(b) Takeuchi, M.; Taniguchi, T.; Ogasawara, K. Chirality 2000, 12, 338.
(4) Taniguchi, T.; Takeuchi, M.; Kadota, K.; ElAzab, A. S.; Ogasawara,
K. Synthesis 1999, 1325.
D
(5) (a) Takano, S.; Higashi, Y.; Kamikubo, T.; Moriya, M.; Ogasawara,
K. Synthesis 1993, 948. (b) Konno, H.; Ogasawara, K. Synthesis 1999, 1135.
(6) Hiroya, K.; Kurihara, Y.; Ogasawara, K. Angew. Chem., Int. Ed. Engl.
1995, 34, 2287.
(7) Ogasawara, K. J. Synth. Org. Chem. Jpn. 1999, 57, 957.
(8) Honzumi, M.; Hiroya, K.; Taniguchi, T.; Ogasawara, K. Chem.
Commun. 1999, 1985.
(9) Takano, S.; Moriya, M.; Higashi, Y.; Ogasawara, K. J. Chem. Soc.,
Chem. Commun. 1983, 177.
10.1021/ol015733i CCC: $20.00 © 2001 American Chemical Society
Published on Web 04/04/2001
Honzumi
