stereospecificity of the cyclization. The absence of the epimeric
spironucleoside with S configuration in the reaction product can
be attributed to the steric interaction between the carbonyl in the
2-position of the base and the bulky-2A substituent as can be
envisaged by inspection of the crystal structure in Fig. 1.
The spironucleosides reported herein correspond to the
first spiro[tetrahydrofuran-2,3A-(1,5,6,7-tetrahydro-3H-[1,3]-
oxazolo[3,4-c]pyrimidine)] nucleosides, possessing a remark-
ably stable orthoamide modification of the C-1A anomeric
position. Further work on the preparation and chemical
transformations of this class of compounds is in progress.
We are grateful to the European Commission for a ‘Marie
Curie’ post-doctoral fellowship to T. G.
O(5A)
C(5A)
O(2)
O(4A)
N(3)
C(6)
O(4)
C(2)
C(4)
C(4A)
N(1)
C(5)
C(1A)
C(2A)
C(3A)
O(3A)
C(7)
O(7)
O(2A)
Footnote and References
* E-mail: chrys@area.bo.cnr.it
Fig. 1 ORTEP drawing of one of the independent molecules of 7 (molecule
1) in the unit cell
1 M. H. el Kouni, F. N. M. Naguib, R. P. Panzica, B. A. Otter, S.-H. Chu,
G. Gosselin, C. K. Chu, R. F. Schinazi, Y. F. Shealy, N. Goudgaon,
A. A. Ozerov, T. Ueda and M. H. Iltzch, Biochem. Pharmacol., 1996,
51, 1687.
2 M. Nakajima, K. Itoi, Y. Tamamatsu, T. Kinoshita, T. Okasaki,
K. Kawakubo, M. Shindou, T. Honma, M. Tohjigamori and T. Haneishi,
J. Antibiot., 1991, 44, 293.
3 (a) S. G. Zavgorodny, Tetrahedron Lett., 1981, 22, 3003; (b) for a recent
approach to 6,1A-anhydro-6-hydroxypsicouridine, see M. S. P. Sarma,
S. Megati, R. S. Klein and B. A. Otter, Nucleosides Nucleotides, 1995,
14, 393.
4 H. Hrebabesky and J. Farkas, Collect. Czech. Chem. Commun., 1974,
39, 1098; A. Grouiller and J. Chattopadhyaya, Acta Chem. Scand., Ser.
B, 1984, 338, 367.
5 Y. Yoshimura, B. A. Otter, T. Ueda and A. Matsuda, Chem. Pharm.
Bull., 1992, 40, 1761.
6 A. Kittaka, N. Yamada, H. Tanaka, K. T. Nakamura and T. Miyasaka,
Nucleosides Nucleotides, 1996, 15, 1447.
7 C. Chatgilialoglu and T. Gimisis, in Free Radicals in Biology and
Environment, ed. F. Minisci, Kluwer, Dordrecht, 1997, pp. 281–292.
8 (a) T. Gimisis and C. Chatgilialoglu, J. Org. Chem., 1996, 61, 1908; (b)
A. Kittaka, H. Tanaka, N. Yamada and T. Miyasaka, Tetrahedron Lett.,
1996, 37, 2801.
ward, three-step chemical transformation, as outlined in
Scheme 1. Standard regioselective protection of the 3A- and
5A-positions with the 1,1,3,3-tetraisopropyldisiloxane-1,3-diyl
group to afford 11, followed by transformation of the
2A-hydroxy group to give the thiocarbonate 12,11 and finally
Barton–McCombie radical deoxygenation in the presence of
(Me3Si)3SiH12 produced the chromatographically less polar
stereoisomeric 2A-deoxyspironucleoside 9. These transforma-
tions, apart from establishing unequivocally the configuration
of the C-1A anomeric centre in 9 and 10, also demonstrated the
inherent stability of the orthoamide structure.
The mechanism for the formation of the spironucleoside
involves generation, under the Sua´rez conditions, of the alkoxyl
radical intermediate 13 which undergoes a [1,5]-radical trans-
location reaction13 to yield the anomeric C-1A radical inter-
mediate 14 [eqn. (1)], which in turn produces the observed
O
H
N
O
9 M. P. Groziak, A. Koohang, W. C. Stevens and P. D. Robinson, J. Org.
Chem., 1993, 58, 4054.
10 P. de Armas, C. G. Francisco and E. Sua´rez, J. Am. Chem. Soc., 1993,
115, 8865; R. L. Dorta, A. Martin, J. A. Salazar, E. Sura´rez and
T. Prange´, Tetrahedron Lett., 1996, 37, 6021.
11 M. J. Robins and J. S. Wilson, J. Am. Chem. Soc., 1981, 103, 932.
12 C. Chatgilialoglu and C. Ferreri, Res. Chem. Intermed., 1993, 19,
755.
HN
O
RO
O
O
[1,5]-radical
translocation
O
•
N
(1)
N
RO
•O
OR
RO
H
OH
RO
OR
13
14
13 A. L. J. Beckwith and K. U. Ingold, in Rearrangements in the Ground
and Excited States Vol. 1, ed. P. de Mayo, Academic, New York, 1980,
pp. 161–310.
orthoamide 6 after oxidation and cyclization. It is worth
pointing out that the steric hindrance induced by the bulky
2A-substituent in the ribo series is likely responsible for the
Received in Glasgow, UK, 5th August 1997; 7/05742C
2090
Chem. Commun., 1997