2706 J . Org. Chem., Vol. 66, No. 8, 2001
Takahashi et al.
tion of specific binding subunits has also been reported.10
To investigate how receptor to receptor-inositol interac-
tions, the synthesis of a series of inositol isomers and
their phosphorylated derivatives would be desiable. For
these reasons, we wished to prepare inositol diastereoi-
somers, which should be good tools for the chemical and
biological research. Herein, we report the novel and
practical syntheses of all nine stereoisomers of inositol
as enantiomerically pure forms starting from 6-O-acetyl-
5-enopyranosides. We further describe the total syntheses
of D-myo-inositol 1,4,5-trisphosphate and D-myo-inositol
1,3,4,5-tetrakisphosphate utilizing this method. Further-
more, the present procedure provides the synthetic
possibility for all isomers of the inositol polyphosphates.
merically pure myo-inositol derivatives.16 These observa-
tions prompted us to examine the PdCl2-catalyzed reac-
tion of 6-O-acetyl-5-enopyranosides with of Hg(II) salts
as promoters. We further envisioned that penta-oxygen-
ated cyclohexanones prepared from 6-O-acetyl-5-enopy-
ranosides might be precursors to all of the inositol
diastereoisomers. Although there are many reports on
the synthesis of each inositol diastereoisomer,17 few
attempts have so far been made at a systematic approach
17p
to all inositol diastereoisomers.
As outlined retrosynthetically in Scheme 1, 6-O-acetyl-
5-enopyranosides prepared from methyl glucoside, meth-
yl galactoside, and methyl mannoside will be converted
into cyclohexanones through Ferrier-II carbocyclization.
Stereoselective reduction of the cyclohexanones will
provide a series of diastereoisomers of inositol in the
protected forms. According to this route, we initially
investigated the carbocyclization mediated by PdCl2.
Resu lts a n d Discu ssion
Gen er a l Str a tegy. Our approach relies on the Ferrier-
II carbocyclization, which is well-established for the
conversion of 6-deoxyhex-5-enopyranosides into the cor-
responding chiral-substituted cyclohexanones.11 This re-
action has been conveniently used for the syntheses of
natural products and carbocyclic analogues of carbohy-
drates.12 There have been several reports concerning the
improvement of the reaction conditions of this rearrange-
ment. Lukacs12a and Ogawa12b have independently de-
veloped the use of a catalytic amount of Hg(II) salts as
effective promoters. Recently, we revealed that the ef-
Ca r bocycliza tion of 6-O-Acetyl-5-en op yr a n osid es
Med ia ted by P d Cl2.18 The substrates, enol acetates,
were prepared from known pyranosides19 as shown in
Scheme 2.
Oxidation of methyl 2,3,4-tri-O-benzylglycosides 1-3
by Moffat’s procedure20 provided the corresponding un-
stable aldehydes, which were immediately treated with
acetic anhydride in the presence of appropriate bases to
afford the desired enol acetates (4-6). In all cases, the
Z-isomers were predominantly obtained, and each isomer
could be isolated through column separation. Thus, we
examined initially the reactivities of the Z- and E-isomers
of 4-6 (4a and 4b, 5a and 5b, 6a and 6b, respectively)
to clarify the catalytic activity of PdCl2 (Table 1).
13
fective use of a catalytic amount (5 mol %) of PdCl2
promoted the conversion of a variety of 6-deoxyhex-5-
enopyranosides into cyclohexanones and found that the
reaction proceeded stereoselectively in good yields.14,15
Independently, the Bender and Prestwich groups have
shown that the terminally substituted enol esters also
undergo the Ferrier-II carbocyclization in the presence
of a stoichiometric amount of Hg(II) salts. Utilizing this
rearrangement, they developed a novel route to enantio-
Treatment of glucoside Z-isomer 4a with 5 mol % of
PdCl2 in aqueous dioxane at 60 °C for 3 h afforded the
penta-oxygenated cyclohexanone in 81% yield as a 49:
24:17:10 (7a , 7b, 7c, and 7d ) diastereoisomeric mixture
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