March, 196-1
ACPLATED 6 - T H I O P U R I N E
20 1
RIBOSIDES
TABLE I ACYLATED6-THIOPURINE RIBOSIDES
SH I
ROC0 OCOR Compound no. 1
Recryst. solventsa
iU.p.,
"C. 252-233'
"%.
-% C 46 Y
found--
H
X
4 4
13 7
320
23,800
H
CHI
Formula CleHisNaOjS
A
2
H
CHa(CHz)z
CzzH3oN40~S
C
206-207
61
53 4
6 1
11 3
53 1
6 2
11 1 320
22,200
3
H
(CHdzCH
CzzHaoXaOiS
D
203-207
60
53 4
6 1
11 3
53 2
6 2
11 7
320
29,700
4
H
CHa(CHd3
Cz6Ha6N40rSC
C
190-192
56
55.1
6 8
10 3
55 3
6 9
1 0 . 4 321
23,100
5
H
CHa(CHn)io
CasHraNaOlS
C
212-214
74
66.5
9.4
6.7
66.7
9.4
6.5
320
24,000
6
H
CHa(CHz)is
CerHiirNaOrS
E
221-222
84
70.8
10.5
5 , 2 70.8 10.5
5.0
322
27,600
7
H
D
202-206
71
71.4
10.0
5 . 2 71.5
5 . 3 321
26,700
8
H
C H ~ ( C H ~ ) I C H = C H - CsrHinsNaOjS (CHZ)? C6Hs CsiHzaNaO7S
219-221d
69
62.4
4.0
9.4
62.7
4.1
9.4
9
H
p-CIC&
239-240
83
33.2
3 0
8.0 53.2
3 1
10
H
p-OzNCsHa
CalH2iClaNiOjS (1) A (2) C E CaiHziNiOiaS
172-176
91
50.9
2.9
13.4 50.8
3.4
11
H
p-CHaOCsHa
CaaHaoNaOiaS
176-177
94
59.5
4.4
8 . 2 59.4
4.6
228 320 8 . 0 245 322 1 3 . 6 264 320 8 . 3 261 323
41,700 25,000 40,600 20,300 33,500 27,400 40,500 22,000
12
NHz
CHa
C I ~ H I Y K S O ~ SE~
203-205e
75 4 4 . 3
4.6
1 6 . 1 44.4
4.7
13
NHz
CzHs
CisHnsNsOiS
C
209-211
61
48.8
5.4
1 5 . 0 48.9
5.6
14
NHz
CHs(CHz)z
C:zHa1NsOiS
C
217-218
79
51.8
6.1
1 3 . 7 51.9
6.3
15
NHz
(CHa)zCH
C2zH31NeoiS
C
211-213
68
51.8
6.1
13.7 51.5
6.1
16
NHz
CHa(CHz)ia
CssHioaNsO~S~ D
17&172
89
67.6
10.2
17
XHz
CbHs
CJIHZ~NSOTS E
225-2280
58
60.9
18
XHz
p-CHaCeHa
CaaIhNsOiSC
212-214
19
XIfz
p-ClCsH4
20
KHz
p-OzNCeHa
+ CIIHZZNSOI~S' B + E
1 6 . 3 264 344 1 4 . 7 264 343 13.4 264 342 1 3 . 6 264 344 6 . 8 262 343 1 1 . 1 227 266 344 10.2 245 340 9 . 8 246 340 1 5 . 1 263 344
3,800 15,100 7,000 22,000 8,600 17,800 7,900 24,000 19,000 34,700 39,700 10,400 21,800 60,300 20,900 44,300 20,000 35,600 24,200
21
NHz
p-CHaOCaHa
CarH3iKisOioSh
X
R
+B
+F
C
+ B,
C
c
C~~HZZC~SK C ~ OD ~S
C
yield C 90 46 8
Ultraviolet absorption (11.p) 1-pH 11--
--pk
cdcd.-1-1 S 4 4 13 6
7 %
6.8
10.0
67.7
10.5
4.1
11.5 6 0 . 5
4.5
83 61.6
4.8
10.6
61.8
5.0
227-228
87
52.0
3.1
9.8
51.6
3.1
191-195
75
48.7
3.1
14.7 48.8
3.4
173-176
64
55.6
4.8
9.5
55.4
4.6
9.8
Xmnx
6
Xmax
238 310 234 305 236 258 310 251 317 251 317 252 318 250 317 250 318 250 317
39,800 16,400 21,600 32,800 24,400 46,400 23,300 8,300 13,600 16,600 20,100 13,200 19,900 13,200 21,400 26,200 30,800 16,500 20,800
244 318 244 323 253 273 314 261 44,200 256 344 19,800 318
43,000 24,300 41,400 14,300 31,400 31,400 27,700 50,000 19,800
a Recrystallization solvents: ( A ) water, (€3) acetone, ( C ) ethyl acetate, ( D ) methanol, ( E ) ethanol, and (F) dichloromethane. c Hemihydrate. d Lit.2a m.p. 206-214'. e Lk4b m.p. 209-211". f Hydrate. 0 Lit.2a m.p. 223.5-227.5.' m.p. 255-256'. hydrate.
Experimental' 2
e
236 13,500 309 23,800 237 10,400 309 20,800 236 15,800 310 28,000 237 12,500 309 23.700 234 14,100 310 22,400 234 19,000 311 27,100 235 16,200 310 24,200 310 23,800
Lit.4b Di-
General Preparation of Acyl Derivatives of 6-Mercaptopurine Riboside and Thioguanosine (see Table I).-To a stirred suspension of 0.02 mole of mercaptopurine riboside in 250 ml. of anhydrous pyridine was added 0.08 mole of the appropriate acid chloride. The resulting solution was heated a t 50-60" for 3 hr. while stirring. The solvent was then removed in vacuo (below 50") and the residue was treated with 500 ml. of distilled water. The crystallized product was filtered and recrystallized from appropriate solvents (see Table I). Drying was accomplished at 100" (0.1 mm.).
A shorter reaction time (1 or 2 hr.) or lower temperature resulted in the recovery of either starting material or mono- or diacylated derivatives. In the case of R = CH,(CHZ)~CH=CH(CH~), or p-CH,CsH4 the water, which was added to induce the and X = H or "2, crystallization of the residue, was decanted and the semisolid residue crystallized upon the addition of 200 ml. of anhydrous methanol. Attempted recrystallizations of unbranched acyl derivatives (R = CHSCH2CH2 through CH3(CHz),CH=CH(CH2)7) from nonpolar solvents (ether, heptane, or benzene) caused the formation of a gel. This difficulty was overcome by recrystallizing these compounds from more polar solvents.
(12) 411 melting points (oorreoted) were taken on a Thomas-Hoover melting point apparatus. The ultraviolet absorption spectra were determined with a Beckman DK-2 spectrophotometer.
Acknowledgment.-The authors wish to thank Drs. Howard w. Bond, Ronald B. Ross, and Harry B. Wood,
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