3250
Vol. 70
ALEXANDER HAMPTON AND DAVIDI. MAGRATH
(2.74 g., 7.8 mmoles),3 and the dried, powdered chloromcrcuri salt was condensed with 2.8 g. (9.5 mmoles) of crystalline 2,3,4-tri-O-acetyl-D-ribosylchloride55 by refluxing in cis-Glycol Optical density a t xylene for 4 hr. By previously described procedure^,^^ Ri test20 Orcinol test27 288 mp, p H 5,2'$ 3.19 g. of crude crystalline 9-D-triacetylribopyranosy1purine 0.084 T 0.78 (IIIa) was obtained, which, when recrystallized from ethyl alcohol, gave 1.1 g. of product (2.9 mmoles, 35%) melting .75 .17 a t 169-171'. .40 .16 Treatment of 570 rng. of IIIa (1.45 Inmoles) for 16 hr. a t &' 1)eterniiiiecl on the material eluted from oiie lane with 5" with methanolic ammonia gave 410 mg. of IIIb. After ,4nil. of water. Assuming a n ernax of 7250 for the products two recrystallizations from n-butyl alcohol, the product, ( e m n a a t 289 = 7250.for the uncharged molecule of 4,s280 mg. (1.1 mmoles), melted a t 250-252' (76L;G yield from diamiiiopyrimidi~ie~~), t h e two slow moving compounds each the acetyl derivative, 1354 over-all yield from I ) . ,4 saniplc contained ca. one mole of ribose per mole of 4,5-diaminopyrecrystallized from ethyl alcohol was analyzed. rimidine. Anal. Calcd. for Cl&?O4T\'4 (252.2): C, 47.5; 1-1, 4.80; S,22.2. Found: C, 47.6; H, 4.73; N , 21.7; [ 0 ( 1 2 0 5 1 ~ m ~ -33.8'; [ C Y ] * O ~ -28.7" ~ ~ ~ (0.5Y0 in water). 6-Methyl-~-ribofuranosylpurine.--A402-mg. (3 niniolesj The absorption spectrum possessed a masimum at 262.5 sample of IIa was converted t o its chloromercuri derivativeii giving 0.900 g. (2.44 mmoles, 81.5%) of product. T h e nip, the position of which did not change in acid or alkali (when determined immediately). T h e err,axa t pH 0.3 was chloroniercuri-6-methylpurine was condensed with 2,3,55.65 X 103, a t PH 7.7 was 6.91 X lo3 and at 12.3 was 7.06 tri-0-acetyl-D-ribosyl chloridej3 prepared from 0.945 g. X lo3. There were two isosbestic points: one a t 281.5 (3.Ommoles) of tetraacetylribof~ranose,~~ and the product was nip with B 2.64 X 103 and one a t cn. 268 nip with e 4.67 X worked up as described below, except t h a t the intermediate IO3. T h e apparent pK, was found t o be 1.80 z!c 0.05 by the triacetyl compound was not obtained in crystalline form. Two recrystallizations of the crude 6-methyl-~-ribofurano- procedure outlined by Fox and S h ~ g a r . ~ ~ sylpurine from ethyl alcohol gave 100 mg. (0.38 mmole, Acknowledgments.-The authors wish to thank 12.5y0) of product in the form of fine needles, m.p. 209Dr. Aaron Bendich for making available samples and 210'. I n another preparation, from 2.6 g. of ITa, a yield spectra of 6-chloro-4,5-diaminopyrimidine, 4,sof 217; was obtained. 4,5-diamino-6-niethylpyrimiA n d . Calcd. for C1lHllOaS.j (266.3): C, 49.6; €1, 5.29; diaminopyrimidine, X, 21.0. Found: C, 49.7; H, 5.50; N, 21.2. dine and 5-amino-4-methylaminopyrimidi11e ; and T h e absorption niasima \vel-e: €265 = 6340 at pH 1, c?61 Dr. Jack J. Fox for the determination of the rota= 7640 at pH 5.5 and 11 (when determined immediately). tion of IIIb. The assistance of Mrs. Orsalia 9-o-Ribopyranosylpurine (IIIb) .-A4 1.00-g. (8.3 mmoles) Intrieri and Mr. Bernard Nidas is gratefully acsample of I was converted to its chloromercuri derivative TABLE
Iv
PROPERTIES OF THE DEGRADATIOX PRODUCTS
+ +
+
knowledged.
( 5 2 ) S. F. X a s o n , J . C h e m Suc., 2071 (1954). (53) J. Davoll, B. L y t h g o e a n d A. R . T o d d , i b i d . , 967 (1848). (54) G. B. Brown, J. Davoll a n d B. A. Lowy, "Biochemical Preparations," Vol. IV, John Wiley a n d Sons, Iuc., L'ew York, S . Y . , 1955, p. 70.
( 3 5 ) €1. Zinner, Bey., 83, 153 (1950). ( 5 6 ) J. J . F o x a n d D. Shugar, Biochim. et B i o p h y s . .,lclu, 9 , :369 (1852). XEW Y O K K
21,
s.Y .
[CONTRIBUTION FROM THE L,ABORAI'OKIES OF THE Sl.0A4N-KEl"rERING D I V I S I O X O F CORNELL U N I V E R S I T Y hfGI)ICAI. CO1.1.EcE
1
Synthesis of an Isopropylidene Derivative of an Alkali-labile Nucleoside: 2 ',3 '-0-Isopropylidene-9-P-D-ribofuranosylpurine BY ALEXANDERHAMPTON A N D DAVIDI. MAGRATH RECEIVEDNOVEMBER 16, 1956
2',3'-O-Isopropy~idene-9-p-~-ribofuranosylpurine can be prepared in good yield by condensation of 9-8-D-ribofuraiiosylpurine with acetone in the presence of zinc chloride or in the presence of p-toluenesulfonic acid. The techniques should be useful for the preparation of isopropylidene derivatives of other alkali-labile purine nucleosides. With p-toluenesulfonic acid the conversion is rapid and quantitative a t room temperature and the method may be applicable t o nucleosides in general.
2 ',3 '-O-Isoprop ylidene-g-o-D-ribofuranosylpurine was desired for the synthesis of 9-P-D-ribofuranosylpurine-5'-pho~phate,~ and a number of procedures for its preparation have been examined. The 2 ',3'-O-isopropylidene derivatives of many nucleoside^^-^ have been prepared by condensations with acetone in the presence of zinc chloride. The rcsulting complex of thc product with zinc chloride (1) T h i s investigation was supported in p a r t b y funds from t h e S a t i o n a l Cancer I n s t i t u t e , National I n s t i t u t e s of Health, Public Health Service, G r a n t No. C-471, t h e Atomic Energy Commission, Contract S o . AT(30-1)-910, a n d f r o m t h e American Cancer Society, upon recommendation of t h e Committee on Growth, h-ational Research Council, G r a n t No. MET-27, ( 2 ) D. I . 3 I a g r a t h a n d G. B. Brown, T H I SJ O U R N A L , 79, 3232 (1857). (:$) P. A . 1,evene a n d R . S.Tipson, J , B i d . Chejn., 121, 131 (1087). (si) J . U a d i l i l e y , J . ( ' / i c , ! ! ~ . S o c . , 1:348 (l!l5l). I . Aliciiclsiiii a i r r l A . K. Twld, tbid , 2171) ( I ' , ) A ! l ) . (1;) 1'. A , I,c\t.uc uud L
