An efficient and versatile synthesis of apiose and some C-1-aldehyde- and/or 2,3-O-protected derivatives

Article abstract of DOI:10.1016/S0040-4039(02)01084-5

The synthesis of 2,3-O-isopropylidene-β-D-apiofuranose (58% overall yield) from L-arabinose via 3-C-(hydroxymethyl)-2,3-O-isopropylidene-D-glycero-tetrose diethyl dithioacetal is reported. Starting from L-arabinose an alternative precursor of D-apiose, 3-C-(hydroxymethyl)-2,3-O-isopropylidene-D-glycero-tetrose dimethyl acetal, was prepared from 2,3-O-isopropylidene-L-threo-tetrodialdose dimethyl acetal and formaldehyde by the aldol-Cannizzaro reaction. Unprotected D-apiose is accessible from both precursors on acid hydrolysis.

Full text of DOI:10.1016/S0040-4039(02)01084-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5405–5406
An efficient and versatile synthesis of apiose and some
C-1-aldehyde- and/or 2,3-O-protected derivatives†
Miroslav Koo´sˇ,* Ju´lia Micˇova´, Bohumil Steiner and Juraj Alfo¨ldi
Institute of Chemistry, Slovak Academy of Sciences, Du´bravska´ cesta 9, SK-84238 Bratislava, Slovakia
Received 23 April 2002; accepted 7 June 2002
Abstract—The synthesis of 2,3-O-isopropylidene-b-
2,3-O-isopropylidene- -glycero-tetrose diethyl dithioacetal is reported. Starting from
-apiose, 3-C-(hydroxymethyl)-2,3-O-isopropylidene- -glycero-tetrose dimethyl acetal, was prepared from 2,3-O-isopropylidene-
-threo-tetrodialdose dimethyl acetal and formaldehyde by the aldol-Cannizzaro reaction. Unprotected -apiose is accessible from
both precursors on acid hydrolysis. © 2002 Elsevier Science Ltd. All rights reserved.
D
-apiofuranose (58% overall yield) from
L-arabinose via 3-C-(hydroxymethyl)-
D
L
-arabinose an alternative precursor of
D
D
L
D
A branched-chain sugar
-glycero-tetrose, which can exist in two furanose forms,
i.e. 3-C-(hydroxymethyl)- -erythrofuranose and 3-C-
(hydroxymethyl)-
-threofuranose]1 occurs widely in
plants as a terminal residue of polysaccharides and
glycosides, duckweed being a particularly rich source. It
D
-apiose [3-C-(hydroxymethyl)-
was first found in parsley in which it occurs as the flavinoid
glycoside apiin.2
-Apiose-containing glycosides, such as
saponins, flavinoids, phenolic or anthraquinone gly-
cosides play an integral role in the biochemistry of plants.3
Recently, some apionucleosides have been reported to be
compatible with antiviral activities.4,5
D
D
D
L
OH
O
CH2OH
CHO
SEt
EtS
SEt
O
EtS
O
OH
CH3
CH3
a
b
CH3
CH3
c
HO
HO
O
O
O
O
HOH2C
H3C
CH3
H2C OH
H2C OH
O
1
2
3
e
OMe
MeO
d
CH3
CH3
OMe
MeO
OMe
MeO
O
O
CH3
CH3
b
CH3
CH3
f
O
O
O
d
OH
CH2OH
O
O
HOH2C
HO
O
H2C OH
H2C OH
OH OH
5
6
7
4
Scheme 1. Reagents and conditions: (a) four steps, 74% overall (Ref. 18a,b); (b) aq. CH2O, EtOH, NaOH, rt, 5 h, 83% of 2, 80%
of 7; (c) HgO, HgCl2, Me2CO, H2O, rt, 3 h, 95% (58% overall from arabinose); (d) Dowex-50 W (H+), H2O, 70°C, 5 h, 95%; (e)
two steps, 40% overall (Ref. 19); (f) NaIO4, MeOH, H2O, 5°C to rt, 1 h, 90%.
Keywords: aldol-Cannizzaro reaction; acetals; dithioacetals.
* Corresponding author. Tel.: +421-2-5910254; fax: +421-2-59410222; e-mail: chemmiro@savba.sk
†
&
This paper is dedicated to Professor Stefan Toma on the occasion of his 65th birthday.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01084-5

5406
M. Koo´sˇ et al. / Tetrahedron Letters 43 (2002) 5405–5406
Numerous syntheses of apiose and its derivatives have
been published,6–17 most of which utilize the base-cata-
lyzed condensation of an excess of formaldehyde with
a suitably O-protected aldehydo-carbohydrate deriva-
tive.9–14 All these procedures are multistep syntheses
with rather low, at most moderate overall yields.
well as routine synthetic procedures used throughout the
synthesis, also makes this method interesting for large-
scale preparations of apiose itself or it may be of more
general utility in preparing suitably protected derivatives.
Acknowledgements
The submitted method is based on the protection of a C-1
aldehyde and all hydroxyl groups of an open chain
pentose, generation of a C-4 aldehyde and its subsequent
aldol-Cannizzaro reaction with formaldehyde to give
apiose with protected functionality at C-1, C-2, and C-3
(Scheme 1). Unlike published methods where C-4 of the
starting pentose becomes the C-1 aldehyde group of the
final apiose derivative, in this approach the head and tail
of the starting pentose chain do not become reversed. Due
to the loss of chirality at C-3 in the product from the
aldol-Cannizzaro step, only the stereochemistry at C-2 in
Financial support for this work by the Scientific Grant
Agency (VEGA, Slovak Academy of Sciences and Min-
istry of Education, Bratislava, Project No. 2/7144/21) is
gratefully appreciated. We thank Dr. V. Pa¨toprsty´, A.
Karovicˇova´ and K. Paule (Institute of Chemistry) for
mass and NMR spectral measurements and elemental
analyses.
References
the starting pentose determines whether
will be formed. Thus, the choice of starting pentose is a
matter of availability of the suitably protected aldehydo-
D- or L-apiose
1. (a) Watson, R. A.; Orenstein, N. S. Adv. Carbohydr.
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pentose and whether the target is
D- or L-apiose.
Considering these facts,
choice and this method affords known9–14 crystalline
2,3-O-isopropylidene-b- - or -apiofuranose in almost
60% overall yield (six steps from arabinose).
D- or L-arabinose is the best
D
L
Thus, starting from
O-isopropylidene- -threo-tetrodialdose diethyl dithio-
L-arabinose, the corresponding 2,3-
L
acetal (1) was prepared by a previously published four-
step procedure18 in 74% overall yield. The aldol-Canniz-
zaro reaction of protected dialdose 1 with a slight excess
of formaldehyde gave 3-C-(hydroxymethyl)-2,3-O-iso-
propylidene-
83% yield. Conventional removal of the dithioacetal
functionality afforded 2,3-O-isopropylidene-b- -apio-
furanose (3) in 95% yield (58% overall from -arabinose).
D
-glycero-tetrose diethyl dithioacetal (2) in
6. Gorin, P. A. J.; Perlin, A. S. Can. J. Chem. 1958, 36, 480.
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hydr. Res. 1971, 20, 251.
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85.
D
L
An alternative precursor suitable for the aldol-Canniz-
zaro reaction, 2,3-O-isopropylidene- -threo-tetrodial-
dose dimethyl acetal (6), was prepared from
2,3-O-isopropylidene- -arabinose dimethyl acetal (5)
(synthesized from -arabinose in two steps according to
the method published19 for the
-isomer). 3-C-(Hyd-
roxymethyl)-2,3-O-isopropylidene- -glycero-tetrose di-
9. Ho, P.-T. Can. J. Chem. 1979, 57, 381.
L
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R. Ch.; Mosher, H. S. J. Org. Chem. 1986, 51, 4802.
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15. Duynstee, H. I.; de Koning, M. C.; van der Marel, G. A.;
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18, 72.
17. Zhao, S.; Petrusˇ, L.; Serianni, A. S. Org. Lett. 2001, 3,
3819.
L
L
D
D
methyl acetal (7) was obtained from 6 in 80% yield under
the same reaction conditions20 as applied to the prepara-
tion of 2. Both 3 and 7, when treated with Dowex 50
W(H+) in water at 70°C, afforded free
D
-apiose (depicted
as the 3-C-(hydroxymethyl)-
Scheme 1) which was characterized as the corresponding
D
-erythrofuranose form 4,
N-benzylphenylhydrazone.9,13
Insummary, wehavedescribedanalternativeandefficient
route to apiose and its new protected derivatives.20
Especially, protection at C-1, O-2 and O-3 provides a
potential for further modification at both hydroxymethyl
groups giving rise to further new interesting apiose
analogs. Moreover, this method affords the highest
overall yields (58%) of the known 2,3-O-protected apio-
furanose 3 presented up until now, which together with
an inexpensive starting material and other chemicals, as
18. (a) Kutterer, K. M. K.; Just, G. Heterocycles 1999, 51,
1409; (b) Kutterer, K. M. K.; Just, G. Synth. Commun.
1999, 29, 3841.
19. Numata, F.; Ishida, H.; Nishimura, K.; Sekikawa, I.;
Azuma, I. J. Carbohydr. Chem. 1986, 5, 127.
20. Typical experimental procedure for aldol-Cannizzaro
reaction is given in Ref. 13. CIMS: 2: m/z 376.5 [M+
C5H5NH]+; 6: m/z 284 [M+C5H5NH]+; 7: m/z 316 [M+
C5H5NH]+.