Synthesis of 8-Ribofuranosyl- and 2-Ribofuranosylamino-7-oxo-7 8-dihydropteridines.
код для вставкиСкачатьTo 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. __ , -~ I Base/solvent system 1 I Piperidine NaOC,H,/HOC,H, KOC(CH,),/HOC(CH3)3 KOC(CH,),/Benzene. r-- ____-. -~ ~ cis:trans [a1 Halogen = CI Reaction conditions Yield (%) [b] cis:trans [a] Halogen = Br Reaction conditions Yield (%) [bl 7.7:1 5.6.1 10 :1 20 :1 48h, 135°C 16h, 100°C 1 h, 100°C 1 h, 100°C 96 53 68 95 5.3 : 1 4.7:l 12 : 1 23 :1 6 h , 100°C 20m111, 80°C [c] 30min, 90°C 30min, 90°C 100 97 95 95 [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 2-Ribofuranosylamino-7-0~07,8-dihydropteridinest**] By Dieter Autenrieth, Helmut Schmid, Klaus Harzer, Manfred Ott, and Wolfgang Pfleiderer"] R' I 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, R R' 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 . 12 927 [(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 investigations[*]. 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 (8). 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). R R' 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 induced 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- [*I 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. 928 Angew. Chem. internat. Edit. j Vol. 10 (1971) j No. 12
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