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Synthesis of 8-Ribofuranosyl- and 2-Ribofuranosylamino-7-oxo-7 8-dihydropteridines.

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To test the scope of this method we have carried out
analogous reactions on the pyrimidines (1)-(3) using
various substituents in positions 2 and 6. The results showed
last place behind the exceptionally enhanced syn-tcis
elimination. The cis isomer, yhich is the product of a syn
elimination, always predominates (see Table).
Table. Dehydrohalogenation of trans-1,2-dihalocyclodecaneto cis- and trans-1-halocyclodecene.
Base/solvent system
Halogen = CI
(%) [b]
Halogen = Br
(%) [bl
10 :1
20 :1
48h, 135°C
16h, 100°C
1 h, 100°C
1 h, 100°C
5.3 : 1
12 : 1
23 :1
6 h , 100°C
20m111, 80°C [c]
30min, 90°C
30min, 90°C
[a] The product ratios were determined by vapor phase chromatography (2.5 m 5% SE 30, 120°C and 2.5 m
20% Carbowax 1540) from the peak areas (no correction was made for substance-dependent differences in
detector response). For identification, the 1-halocyclodecenes were isolated, spectroscopically examined, submitted
to combustion analysis, and reduced to cis- or trans-cyclodecenes with sodium in liquid ammonia. The byproducts were identified by comparison of their retention times with those of independently prepared reference
substances: 3-chloro-cis-cyclodecene, 2-25% [b] (from 2-cyclodecen-1-01 and thionyl chloride, 62 %, b. p.
55-57"C/O.2 torr); 3-bromo-cis-cyclodecene, 3-5% [b] (from cis-cyclodecene and N-bromosuccinimide [9],
67% b.p. 56-57"C/0.05 torr); 8-24% [bj cis- and trans-3-ethoxycyclodecene(from 3-bromo-cis-cyclodecene
and ethanol in the presence of sodium ethoxide, 72%, b.p. 99-101 'C/torr). On the basis of observed retention
times, the remaining by-products formed could be 3-chloro-trans-cyclodecene(1-14% [b]) and C,,H,, hydrocarbons (1-16% [b]).
[b] The yields are corrected for unchanged material (i.e. net yields).-Under the chosen conditions, 14% (in terfbutyl alcohol soIution)-83% (in benzene solution) of the frans-1,2-dichlorocyclodecane was converted and
generally about 70% of the trans-l,2-dibromocyclodecene.
[c] 10% KOH instead of NaOC,H, in ethanol.
The ease of conversion via the two possible stereochemical
pathways appears to be very much less dependent on the
base/solvent system than the syn +trans process in the
dehydrobromination of cyclodecyl bromide'']. Both the
relative and the absolute rates of dehydrohalogenation
change only slightly upon variation of the solvent.
that ribosidation of the 4-amino group with simultaneous
formation of the anomeric 5-nitro-4or- and -4P-ribofuranosylaminopyrimidines (5)-(7) takes place, as expected,
in the presence of aprotic substituents such as halogen,
alkoxy, alkylthio, or dialkylamino. The anomeric mixture
Received: July 29, 1971 [Z 483 IEj
German version: Angew. Chem. 83, 1012 (1971)
[l] For a review see: J . Sicher, Angew. Chem. 84 (1972), in press
[2] Cf. M . Suoboda, 1. Zhuada, and J. Sicher, Collect. Czech. Chem.
Commun. 33, 1415 (1968); J. Zatada, M . Suoboda, and J. Sicher, ibid.
33,4027 (1968); J. Sicher, J. Zaaada, and M . Pankoud, Chem. Commun.
1968, 1147.
[3] J. Sicher and E. Byrne, to be published.
141 Method: K . K Field and P . Kouacic, Synthesis 1969, 135.
[S] By-product: 4% cis-1,6-dibromocyclodecane.
[6] Cf. M . Hauel, M . Suoboda, and J . Sicher, Collect. Czech. Chem.
Commun. 34, 340 (1969).-The carbon tetrachloride used at that time
contained small amounts of ethanol.
[7] The compound, m.p. 84.5-86.5"C, obtained by J. G. Traynham
and D. B. Stone [J. Org. Chem. 35,2027 (1970)l is definitely not cis-1,2dichlorocyclodecane but rather a cyclic sulfite.
[S] J. Zasada, J. Krupirka, and J. Sicher, Collect. Czech. Chem.
Commun. 33, 1393 (1968).
[9] Cf. A. ?: Blomquist, R . E . Burge, and A . C. Sucsy, J. Amer. Chem.
SOC.74,3636 (1952).
Synthesis of 8-Ribofuranosyl- and
By Dieter Autenrieth, Helmut Schmid, Klaus Harzer,
Manfred Ott, and Wolfgang Pfleiderer"]
We have recently shown that the fusion of 4-amino-5nitropyrimidines with fully acylated ribofuranose derivatives['' is a decisive step in the synthesis of pteridine N-8ribofuranosides['].
[*] Dr. D. Autenrieth, Dr. H. Schmid, Dr. K Harzer, Dr. M. Ott,
and Prof. Dr. W. Pfleiderer
Fachbereich Chemie der Universitat
755 Konstanz, Postfach 733 (Germany)
[**I This work was supported by the Deutsche Forschungsgemeinschaft.
Angew. Chem. internat. Edit. 1 Vol. 10 (1971)
/ N o . 12
[(7), 29% yield] obtained from 4-amino-6-dimethylamino-2-methylthio-5-nitropyrimidine( 3 ) was resolved
into its components by preparative layer chromatography ;
the a/P ratio proved to be 2:1, the same as in previous
Absence of a substituent in position 2 is to be avoideh since
this usually leads to lower yields; thus reaction of 4-amino2-dimethylamino-5-nitropyrimidine ( 4 ) and I-O-acetyl2,3,5-tri-O-benzoyl-P-~-ribofuranose
gives a reaction product in 10% yield only. Interestingly, according to NMR
investigations the product is exclusively pure a-riboside
Conversion into the corresponding 7-oxo-7,8-dihydropteridine N-8-riboside was accompanied by the usual
difficulties; relatively good yields of the desired product,
after reduction of the nitro group and subsequent cycliza-
tion by condensation with glyoxylate hemiacetal, were
obtained only in the conversions of (6)-(8) into (9) to
(11) (23, 13, and 20% resp.). The isolated products were
exclusively P-ribosides, irrespective of the nature of the
glycosidic linkage of the starting material. The isolation
and identificationof 6-dimethylamino-9-~-~-ribofuranosylpurine (12)[31,
which is formed alongside (11) probably
by nucleophilic addition of the 4-amino function to the
azomethine grouping of the initially-formed Schiff base
and subsequent hydrolysis, decarboxylation and dehydrogenation, threw some light on the possible side reactions
that take place. On fusion of 2,4-diamino-5-nitropyrimidines (13) and (14) with I-O-acetyl-2,3,5-tri-O-benzoyl-~D-ribofuranose reaction occurs almost exclusively at the 2amino group and affords the chromatographically separable anomeric mixtures (15) and (16), respectively, as
main products. Small amounts of the corresponding 2,4bis(ribosy1amino) derivatives (17) and ( I 8 ) , which also
usually occur as mixtures of the four possible pairs of
anomers (2a, 4 a ; 2a 4 p; 2 P 4 a ; 2 P 4p), are formed as side
products. In the case of 2,4-bis(2,3,5-tri-O-benzoyl-~-ribofuranosylamino)-6-dimethylamino-5-nitropyrimidine( I 7)
we were able to separate the four components by very
carefully planned layer chromatography ;the structure and
configuration of the anomers were then determined by
NMR, and ORD and CD spectroscopy.
Reduction with Raney nickel/H, and subsequent condensation with glyoxylate in methanol led, both in the case of
pure ( 1 5 ~ as
) well as (15B),to partial anomerization of
the glycosidic linkage, since the two anomeric 2-ribosylamino-7-0~0-7,8-dihydropteridine
derivatives ( 20 a) and
(20P) were obtained in different amounts in each case
[from (15x),11% ( 2 0 ~and
) 22% (20P); from ( I S P ) ,
3.5% (20a)and 1.5% (20p)I.Sodiumdithionitereduction
proves to be very satisfactory in the case of the anomeric
mixture (16) since the 5-amino base (19) can be isolated.
Condensation with glyoxylate to the Schiff base and alkoxide-catalyzed cyclization leads, with simultaneous deacylation, to the a,P mixture (21) (25% yield), which is
just as difficult to separate into pure components as its
acetylation mixture (22% yield).
Received: August 24,1971 [Z 494a IE]
German version : Angew. Chem. 83,970 (1970)
[I] H . Rokos and W Pfleiderer, Chem. Ber. 104,770 (1971).
[ 2 ] H . Rokos and W Pfleiderer, Chem. Ber. 104,748 (1971).
[ 3 ] B. R. Baker and J . P. Joseph, J. Amer. Chem. SOC.77, 15 (1955).
General Synthesis of Pteridine N-8-Gly~osides"~~
By Wolfgang Pjleiderer, Dieter Autenrieth,
and Margarete Schranner[']
The relatively difficult accessibility of pteridine N-8-glycosides via 4-glycosylamino-5-nitropyrimidines~11
us to attempt direct N-glycosidation of the pteridine system
by the same method as has been used with success in the
This is based on
case of 2-0~0-1,2-dihydroquinoxalines~~~.
the Birkofer variant13]of the Hilbert-Johnson synthesis[41
which recently has been used with great success, partic-
Prof. Dr. W. Pfleiderer, Dr. D. Autenrieth, and M. Schranner
Fachbereich Chemie der Universitat
775 Konstanz, Postfach 733 (Germany)
p*] This work was supported by the Deutsche Forschungsgemeinschaft.
Angew. Chem. internat. Edit. j Vol. 10 (1971) j No. 12
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synthesis, dihydropteridine, ribofuranose, ribofuranosylamino, oxo
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