Novel spirohydantoins of D-allose and D-ribose derived from glyco-α-aminonitriles

Article abstract of DOI:10.1016/S0040-4039(00)02294-2

The synthesis of 3-spirohydantoin derivatives of D-allose and D-ribose is reported. The key step is the stereoselective conversion of glyco-α-aminonitriles from ulose derivatives of D-glucose and D-xylose using titanium(IV) isopropoxide as a mild and efficient catalyst. Cyclisation of the glyco-α-aminonitriles give the target spirohydantoins.

Full text of DOI:10.1016/S0040-4039(00)02294-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 1499–1502
Novel spirohydantoins of
D
-allose and
D
-ribose derived from
glyco-a-aminonitriles
Denis Postel,* Albert Nguyen Van Nhien, Pierre Villa and Gino Ronco
Laboratoire des glucides, Universite´ de Picardie-Jules Verne, 33 rue Saint Leu, 80039 Amiens, France
Received 12 December 2000; accepted 14 December 2000
Abstract—The synthesis of 3-spirohydantoin derivatives of
D
-allose and
-glucose and D
D
-ribose is reported. The key step is the stereoselective
-xylose using titanium(IV) isopropoxide as a mild
conversion of glyco-a-aminonitriles from ulose derivatives of
D
and efficient catalyst. Cyclisation of the glyco-a-aminonitriles give the target spirohydantoins. © 2001 Elsevier Science Ltd. All
rights reserved.
The herbicidal properties of the natural hydantocidin 1
have stimulated considerable interest in the synthesis of
1 itself and of a wide range of its analogues (Fig. 1).1–4
Sano reported the synthesis of the carbocyclic deriva-
tive 2 of (+)-hydantocidin and the 5-epi-carbocyclic
analogue 3.5 The authors described two routes to spiro-
hydantoins: (1) the Bucherer–Bergs synthesis which
gives thermodynamically controlled spiro products; (2)
the conversion of an a-aminonitrile into a hydantoin
with chlorosulfonylisocyanide followed by acid
catalysed hydrolysis. The synthesis of the a-aminonitrile
intermediate was performed by treatment of the parent
ketone with potassium cyanide and ammonium chloride
in MeOH–H2O. This reaction afforded the epimeric
mixture of a-aminonitriles 4 and 5 and the cyanohydrin
6 (Fig. 1). Herbicidal activity was found not to be
ates for the synthesis of epimeric spirohydantoins of
-mannofuranose and -glucopyranose derivatives
which are potent glycogen phosphorylase inhibitors.6
D
D
The target compounds were synthesised from
D-glucose
and -mannose derivatives by oxidative ring contrac-
D
tion, resulting from nucleophilic attack of methanol at
the lactone carbonyl, followed by migration of the ring
oxygen atom to the carbon of the imine intermediate.
Reaction of a-aminoesters, located at non-anomeric
sites of the sugar, with phenylisocyanates afforded the
corresponding ureas, which were converted into
the corresponding spirohydantoins under basic con-
ditions.1,7,8
Otherwise, carbohydrate spirohydantoins are potential
precursors of a-amino acids by basic or enzymatic
hydrolysis of the hydantoin ring.9
affected when the
D-furanose ring oxygen atom of the
natural product was replaced with a methylene unit.
Fleet used various a-aminolactones as key intermedi-
Figure 1.
Keywords: glyco-a-aminontriles; hydantocidin; spirohydantoin.
* Corresponding author. Tel.: 03 22 82 75 70; fax: 03 22 82 75 68; e-mail: denis.postel@sc.u-picardie.fr
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02294-2

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D. Postel et al. / Tetrahedron Letters 42 (2001) 1499–1502
(toluene–TEA) were unsuccessful. In contrast, car-
bamoylation was readily achieved using BnOC(O)Cl
and PhOC(O)Cl in acetone–H2O and K2CO3 yielding
11 and 12 in 44 and 45% yields, respectively.
We report here the stereoselective synthesis of new
3-spirohydantoins from -glucose and -xylose deriva-
tives by a simple and efficient route. The spirohydan-
toins were synthesised by first converting -glucose into
D
D
D
the ulose 7 by acetonation followed by oxidation
(Scheme 1). Attempts to form the spiro ring directly
using the conditions reported by Sano5 (KCN,
(NH4)2CO3, MeOH–H2O, 70°C) were unsuccessful and
the cyanohydrin 8 was obtained as the exclusive
product. Therefore we turned our attention to an alter-
native route to spirohydantions via a-aminonitrile
intermediates. We previously demonstrated that the
synthesis of such intermediates from various uloses
derivatives was unsuccessful using classical Strecker
synthesis conditions. In contrast, we showed that modi-
fying the reaction by using titanium(IV) isopropoxide
as a mild Lewis acid catalyst,10 the glyco-a-aminoni-
triles 10 could be readily obtained in 80% yield.
The spirohydantoin ring formation was achieved using
a one-pot procedure that consisted of the formation of
the a-carboxamidoisocyanate intermediate 13 which
underwent intramolecular cyclisation in basic condi-
tions. Treatment of the benzyloxycarbonyl derivative 11
with NaOH in H2O–1,4-dioxane at 80°C for 2 h gave a
black mixture and the desired spirohydantoin 14 in low
yield (20%). The darkness of the reaction mixture may
be due to the decarboxylation of the carbamoyl ester to
give the initial tertiary a-aminonitrile 10 which is
known to be unstable under strong basic conditions. In
contrast, 14 was obtained efficiently under the same
conditions from the phenyloxycarbonyl derivative 12 in
80% yield.11
Various routes were used to obtain the target com-
pound 14 from 10 via the a-carboxamidoisocyanate
intermediate 13.
Deprotection of the acetonide group in 14 was achieved
with aqueous HCl at room temperature for 1 h to give
15 in 52% yield after 1 h. Alternatively, 14 was treated
with aqueous trifluoroacetic acid for 1 h to give 16 in
97% yield (Scheme 2).12
Reaction of 10 with both carbon dioxide (MeOH; 75
atm; 85°C; 20 h) and ammonium carbonate (MeOH–
H2O 1/1; 70°C; 4 h) gave the spiro derivative 14 in 80%
yield.
Using a similar strategy, spiro ring formation to give 19
(Fig. 2) was achieved directly from the
D
-ribose a-
An alternative strategy involving cyclisation and cleav-
age also proved successful. The amino group of the
glyco-a-aminonitrile 10 was activated to the isocyanate
13 following formation of either of the carbamoyl esters
11 or 12 followed by basic hydrolysis. The carbamoyl
esters 11 and 12 were obtained by condensation of
benzyl and phenyl chloroformate, respectively, with the
3-NH2 of 10. It is of note that the classical esterification
conditions commonly used in carbohydrate chemistry
aminonitrile derivative 17 with CO2 in 86% yield. Also,
19 was obtained from the phenyloxycarbonyl derivative
18 (83% from 17) under basic conditions in 85% yield.
Treatment of 19 with aqueous trifluoroacetic acid gave
20 in quantitative yield.
In conclusion, we have reported a simple and efficient
strategy for the stereoselective synthesis of spirohydan-
toin at non-anomeric sites of sugars from monosaccha-
Scheme 1. (a) (NH4)2CO3, KCN, MeOH; (b) Ti(OiPr)4, NH3–MeOH; (c) TMSiCN; (d) CO2 75 atm. MeOH; (e) (NH4)2CO3,
MeOH–H2O; (f) ROC(O)Cl, K2CO3, acetone–H2O; (g) NaOH, H2O–1,4-dioxane.

D. Postel et al. / Tetrahedron Letters 42 (2001) 1499–1502
1501
Scheme 2. (h) Aqueous HCl (1N); (i) CF3COOH–H2O, 9/1.
Figure 2.
rides. a-Aminonitriles are employed as key intermedi-
ates, titanium(IV) isopropoxide is used as a catalyst and
finally a one-pot spiroring formation is effected under
basic conditions. Also, partial and total deacetalisation
of the spiro derivatives could be achieved by acid
catalysed hydrolysis.
7. Burton, J. W.; Son, J. C.; Fairbanks, A. J.; Choi, S. S.;
Taylor, H.; Watkin, D. J.; Winchester, B. G.; Fleet, G.
W. J. Tetrahedron Lett. 1993, 34, 6119–6122.
8. Estevez, J. C.; Long, D. D.; Wormald, M. R.; Dwek, R.
A.; Fleet, G. W. J. Tetrahedron Lett. 1995, 36, 8287–
8290.
9. Bravo, P.; Capelli, S.; Meille, S. V.; Seresini, P.; Volonte-
rio, A.; Zanda, M. Tetrahedron: Asymmetry 1996, 7,
2321–2332.
10. Postel, D.; Nguyen Van Nhien, A.; Pillon, M.; Villa, P.;
Ronco, G. Tetrahedron Lett. 2000, 41, 6403–6406.
11. Procedure for the preparation (3R) 3,3-(1,3-diazaspiro-
The compounds synthesised in this programme are
being evaluated for their herbicidal activities and glyco-
gen phosphorylase inhibition. Also, it is of note that
spirohydantoin carbohydrates have the potential to
provide a convenient access to a,a-disubstituted glyco-
a-aminoacids. Studies in this direction and the synthesis
of thio compounds are in progress.
2,4-dioxo)-1,2:5,6-di-O-isopropylidene-h-D-allofuranose
(14): A solution of the phenylcarbamate derivative 16
(450 mg, 1.11 mmol) and NaOH (0.13 g, 3.33 mmol) in
25 mL of 1,4-dioxane/water (1:1) was stirred at 80°C for
1 h. Then the mixture was neutralised with acetic acid
and extracted with ether. The organic layer was dried and
evaporated. The residue was purified by silica gel chro-
matography (hexane/EtOAc 1:1) to afford the spiro-
hydantoin 14 (290 mg, 80%) as a solid. Mp 232–236°C;
[h]2D5 +56 (c 0.76, CHCl3). 1H NMR (CDCl3) l 8.77 (s,
1H, NH), 6.16 (s, 1H, NH), 5.91 (d, 1H, J1,2 3.5 Hz,
H-1), 4.55 (d, 1H, H-2), 4.17 (m, 1H, J4,5 9.0 Hz, H-5),
4.06 (dd, 1H, J5,6a 3.5 Hz, H-6a), 3.96 (dd, 1H, J5,6b 3.5
Hz, H-6b), 3.96 (d, 1H, H-4), 1.54 (s, 3H, CH3), 1.36 (s,
3H, CH3), 1.33 (s, 3H, CH3), 1.24 (s, 3H, CH3), 13C
NMR (CDCl3) l 172.1 (CꢀO), 156.2 (CꢀO), 113.6
(CH3CCH3), 109.9 (CH3CCH3), 104.8 (C-1), 81.5 (C-2),
79.6 (C-4), 74.1 (C-5), 71.2 (C-3), 67.9 (C-6), 26.8 (CH3),
26.6 (CH3), 26.4 (CH3), 24.8 (CH3).
Acknowledgements
We thank the Conseil Re´gional de Picardie and the
Ministe`re Franc¸ais de la Recherche for financial sup-
port, M. Pillon for technical support and G. Mackenzie
for helpful discussions.
References
1. Fairbanks, A. J.; Ford, P. S.; Watkin, D. J.; Fleet, G. W.
J. Tetrahedron Lett. 1993, 34, 3327–3330.
2. Matsumoto, M.; Kirihara, M.; Yoshino, T.; Katoh, T.;
Terashima, S. Tetrahedron Lett. 1993, 34, 6289–6292.
3. Chemla, P. Tetrahedron Lett. 1993, 34, 7391–7394.
4. Harrington, P. M.; Jung, M. E. Tetrahedron Lett. 1994,
35, 5145–5148.
5. Sano, H.; Sugai, S. Tetrahedron 1995, 51, 4635–4646.
6. Bichard, C. J. F.; Mitchell, E. P.; Wormald, M. R.;
Watson, K. A.; Johnson, L. N.; Zographos, S. E.;
Koutras, D. D.; Oikonomakos, N. G.; Fleet, G. W. J.
Tetrahedron Lett. 1995, 36, 2145–2148.
12. Selected spectroscopic values: Complex 15: 1H NMR
(CD3OD) l 5.89 (d, 1H, J1,2 3.5 Hz, H-1), 4.87 (s, 4H,
NH, OH), 4.60 (d, 1H, H-2), 4.18 (m, 1H, J4,5 9.0 Hz,
H-4), 3.72 (m, 2H, J5,6a 5.5 Hz, H-5, H-6b), 3.54 (dd, 1H,
J6a,6b 11.5 Hz, H-6a), 1.57 (s, 3H, CH3), 1.36 (s, 3H,
CH3). 13C (CD3OD) l 174.8 (1C, CꢀO), 158.2 (1C, CꢀO),
113.4 (1C, CH3CCH3), 105.1 (1C, C-1), 82.4 (1C, C-2),
77.8 (1C, C-4), 72.0 (1C, C-3), 71.7 (1C, C-5), 64.3 (1C,
1
C-6), 26.1 (1C, CH3), 25.7 (1C, CH3). Complex 16a: H

1502
D. Postel et al. / Tetrahedron Letters 42 (2001) 1499–1502
NMR (C5D5N) l 12.62 (s, 1H, NH), 8.23 (s, 1H, NH),
NMR (C5D5N) l 12.62 (s, 1H, NH), 8.23 (s, 1H, NH),
5.76 (d, 1H, J1,2 8.0 Hz, H-1), 4.88 (d, 1H, H-4), 4.68 (d,
1H, H-2), 4.59 (m, 1H, J4,5 10.0 Hz, H-5), 4.50 (dd, 2H,
5.84 (d, 1H, J1,2 3.0 Hz, H-1), 4.82 (d, 1H, H-4), 4.75 (m,
1H, J4,5 10.5 Hz, H-5), 4.66 (d, 1H, H-2), 4.40 (dd, 2H,
J
5,6a=J5,6b 5.0 Hz, H-6a, H-6b), 13C NMR (CDCl3) l
J
5,6a=J5,6b 2.0 Hz, H-6a, H-6b), 13C NMR (CDCl3) l
178.0 (CꢀO), 160.6 (CꢀO), 93.7 (C-1), 74.4 (C-2), 73.4
178.2 (CꢀO), 161.0 (CꢀO), 97.2 (C-1), 78.1 (C-2), 73.5
(C-3), 70.8 (C-5), 69.3 (C-4), 63.0 (C-6).
1
(C-3), 70.0 (C-5), 68.4 (C-4), 62.7 (C-6). Complex 16b: H
.