8480
A. E. Koumbis et al. / Tetrahedron Letters 47 (2006) 8479–8481
with those reported in the literature.16 {For (À)-2: [a]D
O
O
O
O
OP
OH
OH
1
(-)-2
À60.2 (c 0.3, H2O), lit.7 [a]D À61.2 (c 0.2, H2O)}.17
O
O
O
O
O
O
Furthermore, there is another point of interest regarding
the above described synthesis. The enantiomer of (À)-2
is equally easy accessible in optically pure form using
the same sequence of reactions but starting from L-arab-
inose.18 This task was also investigated and (+)-2 was
obtained in a similar overall yield.19 {For (+)-2: [a]D
+58.8 (c 0.5, H2O), lit.11 [a]D +58.5 (c 0.5, H2O)}.
3
4
5
Scheme 1. Retrosynthetic analysis.
could derive from the protected lactol 4 (P = a suitable
protecting group), which in turn could derive from
D-erythrose derivative 5. The latter is easily accessible
from D-arabinose and has undoubtedly the correct ste-
reochemistry at the quaternary carbon centre.
In conclusion, the work described in this article presents
a short and efficient synthetic approach towards the
preparation of two natural products, (2R,3R)-2,3-dihy-
droxy-2-methyl-c-butyrolactone [(À)-2] and potassium
(2R,3R)-2,3,4-trihydroxy-2-methylbutanoate (1), mak-
ing use of readily available, multigram quantities of D-
arabinose derived chiron 5 and employing a combined
retrosynthetic chiral pool route. The overall yields for
both targets were approximately 70% in a six-step
sequence involving relatively simple and inexpensive
procedures.
Indeed, hydroxymethyl erythrose 5, available in multi-
gram quantities from D-arabinose,13 was initially deriv-
atized to give tosylate
6 under mild conditions
(Scheme 2). It is noteworthy that under these conditions
the corresponding bis-tosylate was formed only in
traces. Next, the hemiacetal hydroxy group of 6 was
protected yielding a mixture of C-1 epimeric silyl ethers
7 (a and b anomers in a ratio of ca. 3:1). Although it was
very easy to chromatographically separate these two iso-
mers, there was practically no need to do so since both
were equally useful for the on-going synthesis. There-
fore, the mixture of 7 was subsequently reacted with
LiAlH4 in THF under reflux.14 In this way, the 2-C-
methyl-erythrose derivatives 8 were obtained in a very
good combined yield. The removal of the silyl protecting
group was performed under neutral conditions to afford
lactols 9, almost quantitatively. The latter were
smoothly oxidized to give lactone 3.15 The completion
of the synthesis was accomplished by a two-step proce-
dure involving initially, removal of the acetonide group
upon treatment with trifluoroacetic acid [to give (À)-2]
and finally saponification on treatment with aqueous
potassium hydroxide (to yield 1). Both compounds were
found to have identical physical and spectroscopic data
References and notes
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O
O
OH
OR
OTBS
R
i
iii
D
-Arabinose
O
O
O
O
5 R = H
6 R = Ts
7 R = OTs
8 R = H
ii
iv
v
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O
OH
viii
vii
vi
1
(-)-2
3
O
O
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9
Scheme 2. Synthesis of (À)-1 and 2. Reagents and conditions: (i) Ref.
13; (ii) TsCl, pyridine, rt, 90%; (iii) TBSCl, imidazole, CH2Cl2, rt, 98%;
(iv) LiAlH4, THF, 60 °C, 96%; (v) TBAF, AcOH, THF, 0 °C to rt,
99%; (vi) CrO3, pyridine, Ac2O, CH2Cl2, rt, 89%; (vii) TFA, H2O, 0 °C
to rt, 95%; (viii) KOH, H2O, 0 °C to rt, 99%.
12. (a) Koumbis, A. E.; Dieti, K. M.; Vikentiou, M. G.;
Gallos, J. K. Tetrahedron Lett. 2003, 44, 2513–2516; (b)
Gallos, J. K.; Stathakis, C. I.; Kotoulas, S. S.; Koumbis, A.
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