Nucleosides part LXVI I[1]: Synthesis of 4-amino-7(8H) pteridinone-N8-nucleosides-structural analogs of adenosine

Article abstract of DOI:10.1080/15257770903054241

Various 4-amino-7(8H)pteridones (6, 12, 14, 15, 20, 22) have been glycosylated with 1-chloro-2'-deoxy-D-ribofuranose derivatives (25, 26) applying the new DBU-salt method to form the N8-2'-deoxy-D-ribofuranosides (27-36) which can be regarded as 2'-deoxyadenosine analogs. Analogously reacted the 2-N,N-dimethyl-amino-methyleneimino-7(8H)pteridones (43-48) to give preferentially the corresponding N8-ss-D-anomers (49-55). Ribosylation with 1-bromo-2,3,5-tri-O-benzoyl-a-D-ribofuranose (56) proceeded as well with 6, 12, 15, 45, and 46 to yield to N8-ss-D-ribofuranosides 57-61. Sugar deprotection led to the free N8-2'-deoxy-ss-D-ribofuranosides 37-42 and N8-ss-D-ribofurano-sides 62-65, respectively. Glycosylations via the silyl-method under Vorbruggen conditions led with 6, 12 and 15 to the same results, however, 4-amino-6-phenyl-7(8H)pteridone (14) reacted differently forming the N1-ss-D-ribofuranosides (71, 79) and the N1-2'-deoxy - and ss-D-ribofuranosides 73, 74, 77, 78. The assignments of the structures have been achieved by 1H-NMR- and UV-spectra. C,H,N-elemental analyses account for the composition.

Full text of DOI:10.1080/15257770903054241

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Nucleosides Part LXVI I[ ]: Synthesis
of 4-Amino-7(8H)Pteridinone-N8-
Nucleosides—Structural Analogs of
Adenosine
Oliver Jungmann a & Wolfgang Pfleiderer a
a Fachbereich Chemie , Universität Konstanz , Postfach, Konstanz,
Germany
Published online: 29 Jul 2009.
To cite this article: Oliver Jungmann & Wolfgang Pfleiderer (2009) Nucleosides Part LXVI I[ ]:
Synthesis of 4-Amino-7(8H)Pteridinone-N8-Nucleosides—Structural Analogs of Adenosine, Nucleosides,
Nucleotides and Nucleic Acids, 28:5-7, 550-585, DOI: 10.1080/15257770903054241
To link to this article: http://dx.doi.org/10.1080/15257770903054241
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Nucleosides, Nucleotides and Nucleic Acids, 28:550–585, 2009
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1525-7770 print / 1532-2335 online
DOI: 10.1080/15257770903054241
NUCLEOSIDES PART LXVI I[1]: SYNTHESIS OF
4-AMINO-7(8H)PTERIDINONE-N8-NUCLEOSIDES—STRUCTURAL
ANALOGS OF ADENOSINE
Oliver Jungmann and Wolfgang Pfleiderer
Fachbereich Chemie, Universita¨t Konstanz, Postfach, Konstanz, Germany
Various 4-amino-7(8H)pteridones (6, 12, 14, 15, 20, 22) have been glycosylated with 1-
2
chloro-2 ꢁ-deoxy-D-ribofuranose derivatives (25, 26) applying the new DBU-salt method to form
the N8-2 ꢁ-deoxy-D-ribofuranosides (27–36) which can be regarded as 2ꢁ-deoxyadenosine analogs.
Analogously reacted the 2-N,N-dimethyl-amino-methyleneimino-7(8H)pteridones (43–48) to give
preferentially the corresponding N8-ß-D-anomers (49–55). Ribosylation with 1-bromo-2,3,5-tri-O-
benzoyl-a-D-ribofuranose (56) proceeded as well with 6, 12, 15, 45, and 46 to yield to N8-
ß-D-ribofuranosides 57–61. Sugar deprotection led to the free N8-2 ꢁ-deoxy-ß-D-ribofuranosides
37–42 and N8-ß-D-ribofurano-sides 62–65, respectively. Glycosylations via the silyl-method under
Vorbru¨ggen conditions led with 6, 12 and 15 to the same results, however, 4-amino-6-phenyl-
7(8H)pteridone (14) reacted differently forming the N1-ß-D-ribofuranosides (71, 79) and the
N1-2 ꢁ-deoxy-α-and ß-D-ribofuranosides 73, 74, 77, 78. The assignments of the structures have been
achieved by 1H-NMR- and UV-spectra. C,H,N-elemental analyses account for the composition.
Keywords DBU-salt glycosylations; 4-amino-7(8)pteridones; N1- and N8-pteridine-
nucleosides; silyl glycosylations; UV-spectra; pKa-determinations
INTRODUCTION
Our interests in the syntheses of pteridine-N(1)- and N(8)-nucleo-
sides[2–24] are based on the structural similarities to the naturally occurring
pyrimidine - and purine-nucleosides, respectively. Furthermore, most pteri-
dine derivatives are inherently fluorescent and therefore pteridine-based
fluorophores can be applied as new types of building blocks in oligonu-
cleotides synthesis to substitute linker-attached fluorescent probes.[25–27]
Received 16 February 2009; accepted 19 May 2009.
On the occassion of the 70th birthday of Morris J. Robins and in admiration of his important
contributions to purine and nucleosides chemistry.
Address correspondence to Wolfgang Pfleiderer, Fachbereich Chemie, Universita¨t Konstanz,
Postfach 5560, 78457 Konstanz, Germany. E-mail: wolfgang.pfleiderer@unikonstanz.de
550

4-Amino-7(8H)pteridinone-N8-nucleosides
551
In continuation of our investigations of structural analogs of adenosine
and 2ꢁ-deoxyadenosine, we concentrated again on glycosylation reactions
of 4-amino-7(8H)-pteridone (6) and its 2- (12) and 6-phenyl-(14) as well
as 2,6-diphenyl derivatives (15).[15] Since the Hilbert-Johnson-Birkofer
procedure[28] works well in the ribose series, the synthesis of the corre-
sponding 2ꢁ-deoxyribofuranosides leads always to α/ß-anomeric mixture
which have to be seperated by tedious chromatographic techniques. Based
on the phase-transfer glycosylation procedure introduced by F. Seela
et al.[29,30] and the sodium salt approach practised by R.K. Robins et
al.[31] we found some improvement in the pteridine series by applying the
DBU-salts in acetonitrile yielding with 1-chloro-2-deoxy-3,5-di-O-toluoyl-a-D-
ribofuranose in a highly stereospecific manner the blocked 2ꢁ-deoxy-ß-D-
ribofuranosides via an SN2-mechanism.
SYNTHESIS
First we improved the syntheses of the starting pteridine deriva-
tives. 4-Amino-7(8H)-pteridone (6) was obtained from 4,6-diamino-
2(1H)pyrimidinethione (1) by H2O2 oxidation to the corresponding 2-
sulfinic acid (2), followed by hydrolysis with conc. HCl to give 4,6-
diaminopyrimidine (3) in almost quantitative yield. The subsequent nitro-
sation works only well in 2 N HCl yielding 4,6-diamino-5-nitrosopyrimidine
(4) in 82% yield. Catalytic reduction of 4 with Raney-Nickel gave
4,5,6-triaminopyrimidine (5), which was treated with ethyl glyoxylate-
hemiethylacetal and cyclized in MeOH with sodium methoxide to give 69%
of 4-amino-7(8H)pteridone (6) and the isomeric 4-amino-6(5H)-pteridone
(7) in 18% yield, as a side-product. The attempts to synthesize 4,6-diamino-2-
phenylpyrimidine from benzamidine and malononitrile or by the approach
of Howard et al.[32] with malonodiamidine and ethyl benzoate worked only
in very low yields. The interesting variant of E. C. Taylor et al.[33] start-
ing from the silver salt of isonitrosomalonodintrile (8) and benzamidine
hydrochloride (9) worked in α-picoline almost quantitatively to give 4,6-
diamino-5-nitroso-2-phenylpyrimidine (10). Reduction to 4,5,6-triamino-2-
phenylpyrimidine (11) and subsequent condensation with ethyl glyoxylate-
hemiethylacetal afforded 4-amino-2-phenyl-7(8H)-pteridone (12) in 60%
yield. An even simpler and improved approach was found in the Wittig-
Horner-reaction[34] between 10 and ethyl 2-(diethoxyphosphoryl)acetate
(13) yielding compound 12 in 87%. 4-Amino-6-phenyl-7(8H)pteridone (14)
resulted from a Timmis reaction between 4,6-diamino-5-nitrosopyrimidine
(4) and ethyl phenyl-acetate in EtOH/C2H5ONa in 62% yield. Simi-
larly 10 reacted with ethyl phenylacetate to yield 85% of 4-amino-2,6-
diphenyl-7(8H)pteridone (15). Besides the phenyl-substituted 4-amino-
7(8)pteridones (12, 14, 15), we were also interested in the corresponding

552
O. Jungmann and W. Pfleiderer
SCHEME 1
methyl derivatives 19, 20, and 22. 4,6-Diamino-2-methyl-5-nitrosopyrimidine
(17)[33] resulted from the condensation between 8 and 16 and was
then reduced catalytically to 4,5,6-triamino-2-methylpyrimidine (18). Its
reaction with ethyl glyoxylate-hemiethylacetal yielded 37% of 4-amino-
2-methyl-7(8H)pteridone (19). In contrast to earlier results,[35] 4,5,6-
triaminopyrimidine (5) reacted with ethyl pyruvate in AcOH regioselec-
tively, to give 4-amino-6-methyl-7(8H)pteridone (20) in 44% yield. The same
compound resulted also from the condensation of 5 with sodium ethyl oxaly-
lacetate to give, first 4-amino-6-ethoxycarbonylmethyl-7(8H)pteridone (21)
which further gives under acid hydrolysis ester cleavage and decarboxylation
to afford 20. 4-Amino-2,6-dimethyl-7(8H)pteridone (22) was obtained in an
analogous manner via both routes in good yields (Scheme 1).
For the glycosylation reactions of the 4-amino-7-(8H)pteridones 6, 12,
14, 15, 19, and 20, we developed a simplified new procedure on the
basis of Seela’s[29,30] and Robins’[31] ideas by treatment of the DBU (1,8-
diazabicyclo[5.4.0]undec-7-ene) salts (24) with the haloribose 25 and 26,
respectively, in acetonitrile.
A suspension of the starting material in acetonitrile was treated with
one equivalent of DBU and followed by the addition of 1-chloro-3,5-di-

4-Amino-7(8H)pteridinone-N8-nucleosides
553
SCHEME 2
O-(4-chlorobenzoyl)-2-deoxy-α-D-erythro-pentofuranose (25)[36] leading at
room temperature in a highly regioselective manner to the corresponding
N8-2ꢁ-deoxy-ß-D-ribofuranosides 27, 29–33, which were isolated either by
crystallization from CHCl3/MeOH or by chromatographic technique in
34–54% yield. The anomeric α-D-ribosides have been detected chromato-
graphically as minor components and have been isolated in pure form
only in a few cases (34–36). During these reactions it was also noticed
that, minor amounts of the starting material did not react due to their
low solubility. Glycosylation of 12 with 26 in DMF and DMF/CH3CN,
respectively, proceeded in clear solutions but the yields, even after ap-
plying different bases, such as NaH, K2CO3 or KOH led to no improve-
ment. But with DBU, the 4-amino-2-phenyl-8-(3,5-di-O-toluoyl-2deoxy-ß-D-
erythro-pentofuranosyl)-7(8H)pteridone (28) resulted in 49% isolated yield
(Scheme 2).
A general improvement in the glycosylation reactions was expected from
improved solubilities of the starting pteridine derivatives in organic solvents.

554
O. Jungmann and W. Pfleiderer
SCHEME 3
Conversion of the 4-amino group into the 4-dimethylaminomethyleneimino
function by treatment of 6, 12, 14, 15, 20, and 22 with N,N-
dimethylformamide dimethylacetal was performed to give 43–48 in yields
of 84–91% (Scheme 3). Small amounts of side-products especially on
prolonged reaction times were chromatographically detected and identified
as the N8-methyl derivatives.
The glycosylations of the DBU-salts of 43–47 worked well and gave very
good yields, especially, with 45 to 51 in 60%, with 46 to 52 in 86%, and 53 in
71% yield. The deprotection of the sugar moieties to the free pteridine-N-8-
2ꢁ-deoxy-ß-D-erythro-pentofuranosides 37–42 worked very well in high yields
by the Zemplen method[37] in MeOH under CH3ONa-catalysis. The N,N-
dimethylaminomethylene function was rather stable under these conditions
but could be cleaved with K2CO3 in MeOH (Scheme 2).
The new synthetic method has been found to be applicable equally well
for the preparation of the pteridine-N-8-ß-D-ribonucleosides 57–61, whereas
the nucleophilic displacement at the anomeric center of 2,3,5-tri-O-benzoyl-
1-bromo-α-D-erythro-pentofuranose (56)[38] by the attack of the deproto-
nated aglycons in form of their DBU salts, is controlled by the intermediary
formed acyloxonium cation, leading to the formation of a ß-glycosidic link-
age (Scheme 4). In the ribo-series, the direct glycosylation by the DBU-salt
method is only superior to the formerly reported[15] classical Vorbru¨ggen-
silyl approach[39] if the pteridines are amino group protected. Deprotection
by the Zemplen method[37] led again in high yields to the corresponding
4-amino-8-ß-D-erythro-pentofuranosyl-7(8H)pteridones 62–65 (Scheme 4).
During these investigations we also noticed that, the earlier reported
4-amino-6-phenyl-8-ß-D-erythro-pentofuranosyl-7(8H)pteridine[15] and its α-
and ß-D-2ꢁ-deoxyribosides,[40] which were obtained under Hilbert-Johnson-
Birkofer conditions,[41] are not in agreement with the physical data of the
N-8-ribosides synthesized by the DBU-salt method.

4-Amino-7(8H)pteridinone-N8-nucleosides
555
SCHEME 4
We repeated some of the earlier experiments by the silyl method and
converted 4-amino-7(8)pteridone (6), and its 2-phenyl-(12), 6-phenyl-(14)
and 2,6-diphenyl derivatives (15) by treatment with hexamethyl-
disilazane (HMDS) into the corresponding 4-trimethyl-silylamino-7-
trimethylsilyloxypteridines 66–69. Reaction of 66, 67 and 69 with 1-O-acetyl-
2,3,5-tri-O-benzoyl-ß-D-erythro-pentofuranose (70)[41] and BF3-etherate

556
O. Jungmann and W. Pfleiderer
SCHEME 5
as catalyst in CH2Cl2, proceeded in the expected manner under N-8
substitution to 57–59, which were identical with the products obtained
by the DBU-salt method. Unexpectedly, 6-phenyl-4-trimethylsilylamino-7-
trimethylsilyloxypteridine (69) led to a new type of reaction product to
which the revised structure of 4-amino-6-phenyl-1-(2,3,5-tri-O-benzoyl-ß-D-
erythro-pentofuranosyl)-7(8H)pteridone (71) was assigned by spectroscopic
means. Similarly, we reacted 69 with 26 in acetonitrile under catalysis
of trimethylsilyl trifluoromethane-sulfonate to give the anomeric
mixture of 73 + 74, which was separated into the pure components. After
silylation of 4-N,N-dimethylaminomethyleneimino-6-phenyl-7(8)pteridone
(45) reaction with 25 in acetonitrile in the presence of SnCl4 proceeded,
again under N-1 substitution, to give the α,ß-anomeric mixture 77 + 78.
Compound 71 reacted with dimethylformamide dimethylacetal to give
4-N,N-dimethylaminomethyleneimino-6-phenyl-1-(2,3,5-tri-O-benzoyl-ß-D-
erythro-pentofuranosyl)-7(8H)pteridone (79) in high yield (Scheme 5).

4-Amino-7(8H)pteridinone-N8-nucleosides
557
STRUCTURES
The structural determinations of the various reaction products have
1
been achieved by UV- and H-NMR-data. Glycosylations at the 4-amino
group could be excluded since the prepared pteridine-nucleosides showed
1
a normal NH2-signal in the H-NMR spectrum integrating for 2 protons.
Furthermore, the deprotected nucleosides showed no acidic pKa-value
indicating that substitution most likely occured at the 7,8-lactam function.
7-O-glycosylation could be omitted by the fact that the products revealed
no base lability during the deprotection step. The site of glycosylation at
N-8 was derived from a comparison of the UV-spectra with the starting
nucleobases (Table 1).
The close structural analogies can best be seen from the comparisons of
the cations and neutral forms of the nucleobases and their corresponding
free nucleosides as, for example, 6, 37, 63, and 12, 38, 64, and 14, 39,
65, and 15, 40, 66. The same similarities are observed in the 4-N,N-
dimethylaminomethyleneimino series 43, 49, and 44, 50, and 45, 51 and 46,
52, 53, 62. From the comparisons of the UV-spectra of the N-1 with the N-
8-pteridine-nucleosides it is noticed that the longer vinylogous amide reso-
nance between N-1 and the 7-carbonyl group is reflected in a bathochromic
shift of the long wavelength absorption band. The structural differences
between the N-1-(77) and N-8-nucleosides (51) are nicely demonstrated by
the shape of the UV-spectra (Figure 1).
FIGURE 1 UV-spectra of 4-dimethylaminomethyleneimino-6-phenyl-7(8H)pteridone (45), its 8-methyl-,
N-1-(77) and N-8–2ꢁ-deoxyribonucleoside (51) in MeOH.

558
O. Jungmann and W. Pfleiderer
TABLE 1 UV-data of 4-amino-7(8H)pteridones and their nucleosides
pKain
Compound H2O
UV-Absorption in λ
log ε
pH Form
max
6
2,27
7.52 218 249
[245]
290
320
[3.94]
4.07 3.96
[3.71] 3.95
[3.96] 3.98
4.04 3.94
3.96
0.0
5.0
10.0
0.0
+
o
−
+
o
[295] 333 4.32 4.00
[320] 330
290
235
4.37
37
62
2.36
317
336
331
250
253
4.07
4.10
5.0
3.91 MeOH
o
1.74 223 248
218 249
218 253
240
283
293
322 4.26 4.00 3.89 3.95 3.81
0.0
7.0
+
[295] 333 4.38 4.00
337 4.53 4.05
[3.70] 3.92
o
3.86 MeOH
3.93 MeOH
3.96 MeOH
3.92 MeOH
o
o
o
o
27
34
57
12
331
331
4.68
4.72
241
222 [259] [273]
1.97 234 [256]
7.45 222 264
243
2.15 235 [258]
222 266
343 4.81 [4.15] [3.84]
339 4.37 [4.24]
348 4.45 4.28
304
4.15 4.20
4.20
4.19 [4.08] 10.0
4.06 4.14
[3.89] 4.12
[3.96] 4.12 MeOH
4.06 4.17
[3.91] 4.14
[3.99] 4.18 MeOH
0.0
7.0
+
o
341 [354]
305 341 4.33 [4.21]
[316] 353 4.39 4.21
[328] 354 4.45 4.26
306
4.59
−
+
o
38
63
0.0
5.0
220 266
o
1.73 239 [260]
221 267
346 4.36 [4.26]
0.0
5.0
+
[315] 354 4.43 4.25
[323] 355 4.43 4.30
o
221 267
o
28
29
58
14
[229] 240 [267] [320] 354 [4.62] 4.64 [4.28] [3.93] 4.10 MeOH
229 239 [266] [323] 355 4.61 4.61 [4.27] [3.92] 4.10 MeOH
o
o
o
226
268 [320] 357 4.79
4.30 [3.94] 4.14 MeOH
2.27 222 [240]
7.69 219 [247] 260
300
354 4.46 [4.19]
358 4.39 [4.06] 4.14
4.04 4.23
4.22
0.0
7.0
+
o
233
260
352 4.47
353 4.39 [4.16]
360 4.36 [4.09] 4.14
366 4.38 [4.12] 4.17
369 4.42 [4.13] 4.19
4.24
4.20
3.99 4.17
4.14
10.0
0.0
7.0
−
+
o
39
2.41 222 [241]
301
218 [249] 261
220 [246] 264
220 [246] 265
4.16
4.19 MeOH
4.20 MeOH
10.0
−
64
30
15
o
238
1.91 229
7.99 222
[268
366 4.53
[4.01]
o
[250] [320] 372 4.38
272
[4.29] [4.06] 4.40 −0.5
+
378 4.37
367
[316] 373 4.42 [4.32]
377 4.35
4.28
4.37
4.28
[3.97] 4.37
4.38
7.0
11.0
0.0
7.0
11.0
0.0
o
250
4.59
−
+
o
−
+
o
o
o
o
40
65
2.70 232 [242]
222
222
1.84 233
[220]
266
270
4.26
4.31
383 4.50
4.37
[263] [317] 375 4.28
271
272
[270]
270
[4.08] [3.98] 4.40
4.29
4.30
[4.33]
4.37
379 [4.35]
385 [4.50]
388 4.69
4.36
7.0
[220]
232
226
4.36 MeOH
4.37 MeOH
4.39 MeOH
31
59
19
387 4.79
2.80 220
8.32
235
2.88 220
291
315 [341] 4.31
4.03 3.97 [3.72] 0.0
4.11 [3.67] 4.03 [3.94] 5.0
4.04 [3.93] 13.0
+
250 [290] 334 [345]
330 [343] 4.38
320 [336] 4.32
o
−
+
o
20
41
291
4.11 3.98 [3.79] 0.0
8.39 218 243 [291] 326 [343] 4.37 4.07 [3.82] 4.02 [3.89] 5.0
231 326 [338] 4.41 4.08 [3.96] 13.0
248 [292] 329 4.09 [3.71] 3.93 MeOH
−
o

4-Amino-7(8H)pteridinone-N8-nucleosides
559
TABLE 1 UV-data of 4-amino-7(8H)pteridones and their nucleosides (Continued)
pKain
Compound H2O
UV-Absorption in λ
log ε
pH Form
max
32
35
22
241
240
333
329
293 [320]
245 [291] 331
4.66
4.68
3.96
3.94
MeOH
MeOH
0.0
5.0
13.0
MeOH
MeOH
0.0
4.0
8.0
o
o
2.96 220
8.59
4.35
4.14 [3.85]
4.08 [3.77] 4.03
4.41 [4.22] 4.12
4.08 [3.74] 3.95
+
o
232 [250]
327
−
o
o
42
33
43
250 [298] 333
241
333
315
332
4.66
3.96
4.08 3.99
4.01
2.16 220
290
4.37
4.43 4.07
346 4.24
+
5.23 217 248
219
o
281
282
270
263
299
301
267
258
289
290
293
293
272
269
302
302
305
305
303
306
260
4.14
4.18
−
o
49
44
241
333
4.65 4.03 4.15
MeOH
1.96 233
5.48 220
222
337 [344] 4.44
349 4.43
355 4.45
355
4.46 4.33 [4.17] 0.0
+
4.39
4.49
4.27
4.28
4.0
8.0
o
−
o
50
45
235
4.68 4.50
4.21
4.26 MeOH
2.22 221
5.31 220
222
345 4.36
360 4.35
371 4.31
372 4.33
374
4.25
4.24
4.25
0.0
4.0
8.0
+
4.26
4.40
4.44
o
−
o
o
222
4.27 MeOH
4.24 MeOH
4.21 MeOH
51
60
46
238
228
4.70 4.50
4.74 4.47
4.40
378
o
1.91 231
5.42 233
225
363 4.43
377 4.40
377 4.47
383 4.49
388
4.44
4.40
4.42
0.0
4.0
8.0
+
4.46
4.59
4.57
o
−
o
o
o
o
225
4.41 MeOH
4.38 MeOH
4.33 MeOH
4.37 MeOH
4.31 MeOH
0.0
52
53
54
61
47
237
235
237
227
4.72 4.62
4.69 4.57
4.74 4.62
4.75 4.53
386
379
390
o
2.80 220
307
4.17
4.19 4.20
+
5.82 230 255 [281] 314 [329] 4.03 4.07 [3.93] 4.09 [3.98] 4.0
o
217
238
278
281 [325] 336 4.64
309 4.15 4.19
342 4.19
4.22
4.30 [4.23] 4.24 MeOH
4.19 0.0
4.28
8.0
−
o
55
48
2.94 220 256
+
5.90 225 251 [283] 317 [331] 4.03 4.07 [3.93] 4.09 [3.98] 4.0
o
222
229
1.56 219
229
279
263
257
263
265
344 4.19
370 4.83
354 4.34
362 4.93
367 4.40
367 4.68
366 4.71
352 4.40
361 4.43
365 4.44
366 4.46
397 4.74
393 4.72
400 4.80
4.19
4.51
4.28
4.37
4.42
4.29
4.29 MeOH
8.0
−
o
71
72
4.22
4.25
4.28 MeOH
4.20 MeOH
4.23 MeOH
0.0
7.0
+
o
230
233
233
o
o
o
73
74
75
[260]
[260]
[4.43]
[4.38]
2.40 221
229
300
4.00 4.25
4.25
0.0
7.0
+
262
264
264
4.37
4.39
4.39
4.50
4.47
4.53
o
230
231
238
237
4.26 MeOH
4.26 MeOH
4.44 MeOH
4.42 MeOH
4.46 MeOH
o
o
o
o
76
77
78
79
302
302
303
228
o

560
O. Jungmann and W. Pfleiderer
The H-NMR-spectra (exper. part) are also in full agreement with the
1
proposed structures of the newly synthesized pteridine-nucleosides. The
assignments of the site of glycosylation was derived first from comparisons
of the signals of 39 and 75 as well as 64 and 72 indicating that, in the
N-1 nucleosides the H-C(2) is shifted to lower field compared to H-C(2)
in the N-8-analogs and the H-C(1ꢁ) shifted in the opposite direction to
higher field in the N-1-compared to the N-8 nucleosides. These shifts are
influenced by the sugar moiety in the first and by the 7-carbonyl function in
the second case. A confirmation of this assignment was also drawn from
the ROESY-spectra which showed no correlation peaks between H-C(2)
and the sugar protons in the N-8 nucleosides whereas the cross couplings
were detected in the N-1-nucleosides. These relations furthermore proved
the ß-configuration of the glycosidic linkage. The ß-configuration in the
2ꢁ-deoxynucleosides (27–33, 37–42, 49–55, 73 and 79) is based on the ꢀδ
shift difference[43] of the Hß-C(2ꢁ) and Hα-C(2ꢁ) in D6-DMSO in the order
of 0.63–1.01 ppm whereas the a-anomers (34–36, 54, 74, 76, and 78) show
in general no splitting of the signals.
EXPERIMENTAL
Melting points were taken on a Bu¨chi Melting Point B-545 apparatus and
are uncorrected. Products were dried under high vacuum. TLC: precoated
silica gel thin-layer sheets 60 F 254 from Merck (Darmstadt, Germany)
and cellulose sheets F 1440 LS 254 from Schleicher & Schuell. Column
chromatography (CC): silica gel 60 from Merck and flash chromatography
(FC): silica gel (30–60 µm) from Baker. UV/VIS: Perkin-Elmer Lambda 5;
λmax in nm (log ε). 1H-NMR: Bruker AC 250 and Bruker DRX 600; δ in ppm
rel. to SiMe4 or CDCl3 (DMSO-d6) as internal standard. The pKa-values were
determined by the spectrophotometric method.[42] Elemental analyses
were performed by the analytical lab of the Department of Chemistry,
Konstanz University.
4,6-Diaminopyrimidine-2-sulfinic acid (2)[44]
A solution of 4,6-diamino-2(1H)pyrimidinethione (1)[45] (50 g, 0.35
mol) in 2N NaOH (220 ml) was cooled by ice and then within 45 minutes
H2O2 (3%; 750 ml) was added dropwise with stirring. It was stirred at room
temperature for 30 minutes and thern acidified by glacial acetic acid. The
resulting precipitate was collected, washed with H2O and EtOH and dried at
60◦ to give 58.3 g (96%) of colorless crystals of m.p. 167–170◦C (decomp.).
UV (MeOH): 263 (3.89). Anal. For C4H6N4O2S (174.2) Calcd: C 27.58, H
3.47, N 32.17. Found: C 27.19, H 3.34, N 31.88.

4-Amino-7(8H)pteridinone-N8-nucleosides
561
4,6-Diaminopyrimidine Hydrochloride (3)[44]
Under vigorous stirring, compound 2 (40 g, 0.23 mol) was added in
small portions into conc. HCl (120 ml). After 30 minutes the precipitate was
collected, washed with acetone, and ether, and dried at 60◦ to give 32.4 g
(96%) of a colorless solid of compound 3 of m.p. 200–202◦C. UV (MeOH):
263 (3.62). Anal. For C4H6N4 × HCl (146.6) Calcd: C 32.78, H 4.13, N 38.22.
Found: C 32.66, H 3.95, N 37.78.
4,6-Diamino-5-nitrosopyrimidine (4)[44]
A solution of 3 (8.0 g, 55 mmol) in 2 N HCl (250 ml) was cooled
in ice and then NaNO2 (4.2 g, 62 mmol) in H2O (15 ml) was added
dropwise. Stirring was continued for 30 minutes at 0–5◦ and then 2 hours
at room temperature. The violet solution was neutralized with NaHCO3,
the resulting precipitate collected, suspended in H2O and heated to 80◦C,
filtered, washed with MeOH and dried to give 6.3 g (82%) of blue crystals of
4 of m.p. >350◦C. UV (MeOH): 224 (4.07), 346 (4.02), 643 (1.80). 1H-NMR
(DMSO-d6): 10.05 (s, 1H, NH2); 9.12 (s, 1H, NH2); 8.44 (s, 1H, NH2); 8.05
(s, 1H, NH2); 7.92 (s, H-C(2)). Anal. For C4H5N5O (139.1) Calcd: C 34.53,
H 3.62, N 50.34. Found: C 34.35, H 3.66, N 49.99.
4,5,6-Triaminopyrimidine (5)[46]
A solution of 4 (7.8 g, 56 mmol) in MeOH (200 ml) and 1 N NaOH
(10 ml), was reduced with H2 and Raney-nickel (1.2 g) in a shaking appa-
ratus. After uptake of the theoretical amount of H2 in 2 days, the catalyst
was filtered off, the filtrate evaporated, and the residue was recrystallyzed
from H2O (100 nl) and charcoal. On cooling, 6.78 g (97%) of colorless
crystals of 5 of m.p. 257◦C were obtained. UV (MeOH): 277 (3.94), 281
1
(4.00). H-NMR (DMSO-d6): 7.45 (s, H-C(2)); 5.57 (bs, 4H, 2 NH2); 3.75
(bs, H2N-C(5)). Anal. For C4H7N5 (125.1) Calcd: C 38.39, H 5.64, N 55.96.
Found: C 38.31, H 5.59, N 55.87.
4-Amino-7(8H)pteridone (6)[13]
To a solution of Na (10 g) in abs. MeOH (500 ml) 4,5,6-
triaminopyrimidine (12.5 g, 0.1 mol) was added and followed by ethyl
glyoxylate-ethyl-hemiacetal (30 ml). After stirring the soln for 18 hours at
room temperature, the solution was evaporated to half of the volume, then
H2O (500 ml) was added and acidified by AcOH to pH 5. The precipitate
was collected and recrystallized from DMF/H2O to give 11.29 g (69%) of
a colorless crystal powder of 6 of m.p. >350◦C. 1H-NMR (DMSO-d6): 12.65
(s, H-N(8)); 8.15 (s, H-C(2)); 7.90 (s, H-C(6)); 7.65 (bs, NH2). Anal. For

562
O. Jungmann and W. Pfleiderer
C6H5N5O (163.1) Calcd: C 44.17, H 3.09, N 42.93. Found: C 43.85, H 3.15,
N 42.92.
Evaporation of the filtrate and recrystallization of the residue gave 2.94 g
(18%) of 4-amino-6(5H)-pteridone (7). pKa: 3.39. UV (pH 0): 225 (4.52),
280 (4.31), [345 (3.20)], [360 (3.08)]. (pH 12): 255 (4.25), [277 (3.89)],
367 (3.86), [384 (3.76)].
Silver Salt of Isonitrosomalononitrile (8)
A solution of malononitrile (20 g, 0.3 mol) in AcOH (60 ml) + H2O (60
ml) was cooled in ice and then NaNO2 (23 g, 0.33 mol) in H2O (100 ml) was
dropwise added under stirring. The solution was kept at room temperature
in the dark overnight and then a solution of AgNO3 (46 g, 0.3 mol) in
H2O (100 ml) was added. The precipitate was collected,washed with H2O,
MeOH, and ether, and dried in high vacuum at 60◦C to give 57.6 g (95%)
of a yellow solid of 8 of m.p. >350◦C. UV (MeOH): 291 (4.07), 407 (1.90).
Anal. For C3AgN3O (201.9) Calcd: C 17.85, N 20.81. Found: C 17.45, N
20.66.
Benzamidine Salt of Isonitrosomalononitrile[33]
To a soln of benzamidine hydrochloride (9) (50.7 g, 0.32 mol) in MeOH
(320 ml) 8 was added in small portions (72.0 g, 0.36 mol) under stirring
at room temperature. After 1 hour the AgCl was filtered off, the filtrate
evaporated to dryness, and the residue was recrystallized from EtOAc (500
ml) to give 50.2 g (87%) of yellowish crystals of m.p. 146◦C. UV (MeOH):
228 (4.14), 290 (4.09). Anal. For C10H9N5O (215.2) Calcd: C 55.81, H 4.21,
N 32.54. Found: C 56.01, H 4.19, N 32.36.
4,6-Diamino-5-nitroso-2-phenylpyrimidine (10)[33]
A solution of the benzamidine salt of isonitrosomalononitrile (66.5 g,
0.31 mol) in 2-methylpyridine (330 ml) was heated in an oilbath to 160◦C
for 3 hours. After cooling to room temperature H2O (330 ml) was added
to separate a green precipitate which was washed with H2O and MeOH and
dried in vacuum at 80◦C to give 63.4 g (95%) of 10 of m.p. 235–237◦C. UV
(MeOH): 290 (4.13), 353 (4.30), 623 (1.74). 1H-NMR (DMSO-d6): 10.18 (s,
1H, NH2); 9.12 (s, 1H, NH2); 8.49 (s, 1H, NH2); 8.37 (m, 2H, arom. H); 8.10
(s, 1H, NH2); 7.49 (m, 3H, arom. H). Anal. For C10H9N5O (215.2) Calcd: C
55.81, H 4.21, N 32.54. Found: C 55.66, H 4.24, N 32.29.

4-Amino-7(8H)pteridinone-N8-nucleosides
563
4,5,6-Triamino-2-phenylpyrimidine (11)[33]
A suspension of 10 (14.0 g, 65 mmol) in MeOH (200 ml) was reduced
under H2 atmosphere in presence of Pd/C (150 mg, 5%) in a shaking
apparatus. The reaction solution was heated, the catalyst filtered off, and
the filtrate evaporated to dryness. The residue was recrystallized from H2O
(350 ml) with charcoal to give 10.2 g (78%) of brownish needles of 11 of
m.p. 186–188◦C. UV (MeOH): 223 (4.50), 290 (4.08). 1H-NMR (DMSO-d6):
8.14 (m, 2H, arom. H); 7.32 (m, 3H, arom. H); 5.67 (bs, 4H, 2 NH2); 3.96
(bs, 2H, H2N-C(5)). Anal. For C10H11N5 (201.2) Calcd: C 59.69, H 5.51, N
34.80. Found: C 59.49, H 5.61, N 34.90.
4-Amino-2-phenyl-7(8H)pteridone (12)[13]
a) To a solution of Na (2.5 g) in absolute MeOH (200 ml) 4,5,6-triamino-
2-phenylpyrimidine (11) (5 g, 25 mmol) was added and followed by ethyl
glyoxylate-ethylhemiacetal (15 ml). After stirring for 24 hours at room
temperature was evaporated to half of the volume, then H2O (300 ml)
and charcoal were added. The reaction mixture was heated, filtered hot,
and acidified by AcOH to pH 5. After cooling the precipitate was collected
and dried at 60◦C to give 3.59 g (60%) of a yellowish crystal powder of 12 of
m.p. 330–332◦C.
b) To a suspension of NaH (0.3 g, 12.5 mmol) in THF (100 ml) ethyl
2-(diethoxyphosphoryl)acetate (13) (2.5 ml, 12.5 mmol), dissolved in THF
(10 ml), was added dropwise under stirring. After 30 minutes, 10 (2.15 g,
10 mmol) was added and stirring continued for 1 hour. The resulting
precipitate was collected and recrystallized from DMF to give 2.1 g (87%)
1
yellowish powder of 12 of m.p. 331–332◦C. H-NMR (DMSO-d6): 12.70 (s,
H-N(8)); 7.66 (m, 2H, arom. H); 7.21 (s, H-C(6)); 6.98 (bs, NH2); 6.87 (m,
3H, arom. H). Anal. For C12H9N5O (239.2) Calcd: C 60.25, H 3.79, N 29.27.
Found: C 60.11, H 3.88, N 28.95.
4-Amino-6-phenyl-7(8H)pteridone (14)[13]
A mixture of 4 (8.0 g, 58 mmol) and ethyl phenylacetate (11.1 ml, 70
mmol), in a solution of Na (3.0 g, 130 mmol) in absolute EtOH (250 ml),
was heated under reflux for 3 h. The precipitate was collected after cooling.
then dissolved in hot H2O (300 ml), and acidified with 2 N HCl to pH 3. The
precipitate was collected after cooling and recrystallized from DMF to give
8.6 g (62%) of a yellowish powder of 14 of m.p. >350◦C. 1H-NMR (DMSO-
d6): 12.82 (s, H-N(8)); 8.47 (m, 2H, arom. H); 8.18 (s, H-C(2)); 7.77 (bs,
NH2); 7.46 (m, 3H, arom. H). Anal. For C12H9N5O (239.2) Calcd: C 60.25,
H 3.79, N 29.27. Found: C 59.91, H 3.86, N 28.87.

564
O. Jungmann and W. Pfleiderer
4-Amino-2,6-diphenyl-7(8H)pteridone (15)[13]
a) A mixture of 10 (2.15 g, 10 mmol) and ethyl phenylacetate (1.91
ml, 12 mmol) in a solution of Na (0.28 g, 12 mmol) in absolute EtOH
(100 ml), was heated under reflux for 3 hours. The yellow precipitate was
collected after cooling. suspended in H2O (100 ml) and acidified by AcOH
to pH 5. The solid was collected, dried at 100◦C to give 2.68 g (85%) of a
chromatographically pure yellow powder of 15 of m.p. >350◦C.
b) A mixture of 11 (2.0 g, 10 mmol) and ethyl phenylglyoxylate (2.0 ml
12 mmol) was heated in EtOH (50 ml) for 2 hours under reflux. After
cooling the precipitate was collected and recrystallized from DMF/H2O
2:1 to give 2.81 g (89%) of a yellow crystal powder of 15 of m.p. >350◦C.
1H-NMR (DMSO-d6): 12.80 (s, H-N(8)); 8.54 (m, 2H, arom. H); 8.36 (m,
2H, arom. H); 7.73 (bs, NH2); 7.48 (m, 6H, arom. H). Anal. For C18H13N5O
(315.3) Calcd: C 68.56, H 4.16, N 22.21. Found: C 68.23, H 4.21, N 21.97.
Acetamidine Salt of Isonitrosomalononitrile[33]
To a solution of acetamidine hydrochloride (16) (15.0 g, 0.157 mol) in
MeOH (150 ml), was added in small portions 8 (35.0 g, 0.173 mol) under
stirring at room temperature. After 1 hour, the AgCl was filtered off, the
filtrate was evaporated to dryness, and the residue was recrystallized from
EtOAc (1.3 l) to give 20.8 g (87%) of yellowish crystals of m.p. 138–140◦C.
UV (MeOH): 290 (4.07). Anal. For C5H7N5O (153.1) Calcd: C 39.22, H
4.61, N 45.73. Found: C 39.39, H 4.61, N 45.77.
4,6-Diamino-5-nitroso-2-methylpyrimidine (17)[33]
A solution of the acetamidine salt of isonitrosomalononitrile (14.43 g,
94 mmol) in 5-ethyl-2-methylpyridine (72 ml) was heated in an oilbath to
180◦C for 20 minute. After cooling to room temperature, EtOH (100 ml)
was added and the green precipitate was collected, washed with EtOH and
ether, and dried in vacuum at 80◦C to give 13.62 g (95%) of a green crystal
powder of 17 of m.p. 306◦C (decomp.). UV (MeOH): [225 (4.17)], 343
1
(4.10), 622 (1.74). H-NMR (DMSO-d6): 10.02 (s, 1H, NH2); 8.94 (s, 1H,
NH2); 8.33 (s, 1H, NH2); 7.94 (s, 1H, NH2); 2.19 (s, H3C-C(2)). Anal. For
C5H7N5O (153.1) Calcd: C 39.22, H 4.61, N 45.73. Found: C 39.61, H 4.56,
N 45.56.
4,5,6-Triamino-2-methylpyrimidine (18)
A suspension of 17 (12.0 g, 13.1 mmol) in MeOH (250 ml) was reduced
under H2 atmosphere in presence of Pd/C (1.0 g, 10%) in a shaking
apparatus for 6 hours. The mixture was heated, charcoal was added, the

4-Amino-7(8H)pteridinone-N8-nucleosides
565
hot solution was filtered and the filtrate was evaporated to dryness. The
residue was dissolved in hot MeOH (60 ml), toluene (150 ml) was added
and the solution was then stored in the icebox over night. The precipitate
was collected and gave after drying 9.25 g (85%) of a brownish solid of 18 of
m.p. 240–242◦C. The substance can be sublimed at 190◦C/0.001 bar to give
1
a colorless solid. UV (MeOH): 279 (3.91). H-NMR (DMSO-d6): 5.54 (bs,
4H, 2 NH2); 3.54 (bs, 2H, H2NC(5)); 2.06 (s, H3C-C(2)). Anal. For C5H9N5
(139.2) Calcd: C 43.15, H 6,52, N 50.33. Found: C 43.33, H 6.54, N 50.71.
4-Amino-2-methyl-7(8H)pteridone (19)
To a solution of Na (1.0 g, 43 mmol) in abs. MeOH (50 ml), 4,5,6-
triamino-2-methylpyrimidine (18) (2.5 g, 18 mol) was added and followed
by ethyl glyoxylate-ethylhemiacetal (5.33 g, 136 mmol). After stirring for 12
hours at room temperature, H2O (150 ml) was added, heated with charcoal,
filtered, and acidified by AcOH to pH 5. After cooling, the precipitate was
collected, recrystallized from DMF (350 ml) + H2O (250 ml) and dried at
60◦C to give 1.13 g (37%) of a colorless crystal powder of 19 of m.p. >300◦C
1
(decomp.). H-NMR (DMSO-d6): 12.58 (s, H-N(8)); 7.85 (s, H-C(6)); 7.60
(bs, NH2); 2.32 (s, H3C-C(2)). Anal. For C7H7N5O (177.2) Calcd: C 47.46,
H 3.98, N 39.53. Found: C 47.25, H 4.17, N 39.76.
4-Amino-6-methyl-7(8H)pteridone (20)
a) To a solution of 5 (2.0 g, 16 mmol) in AcOH (20 ml) was added ethyl
pyruvate (2.2 ml, 19 mmol) and then heated under reflux for 2 hours. After
cooling the precipitate was collected, recrystallized from DMF/H2O (1:1,
350 ml) and dried at 60◦C to give 1.25 g (44%) of a colorless solid of 20 of
m.p. >360◦C (decomp.).
b) A solution of 21 (2.2 g, 8.8 mmol) in 1 N HCl (70 ml) was heated
in an oilbath to 120◦C for 1.5 hours. Charcoal was added, filtered hot, and
the filtrate buffered by NaHCO3 to pH 5. The precipitate was collected and
recrystallized from DMF/H2O (1:1, 250 ml) to give 1.0 g (64%) of a colorless
1
solid of 20 of m.p. >360◦C (decomp.). H-NMR (DMSO-d6): 12.56 (s, H-
N(8)); 8.12 (s, H-C(2)); 7.85 (s, H-C(6)); 7.45 (bs, 1H, NH2); 7.35 (bs, 1H,
NH2); 2.34 (s, H3C-C(6)). Anal. For C7H7N5O (177.2) Calcd: C 47.46, H
3.98, N 39.53. Found: C 47.10, H 4.17, N 39.29.
4-Amino-6-ethoxycarbonylmethyl-7(8H)pteridone (21)
A solution of 5 (1.46 g, 12 mmol) in AcOH (20 ml) was treated with
sodium diethyl oxalylacetate (3.0 g, 14 mmol) in an oilbath at 100◦C for
1 hour. The suspension was treated with H2O (40 ml) and after cooling the
precipitate collected and recrystallized from AcOH (20 ml) with charcoal to

566
O. Jungmann and W. Pfleiderer
give 1.94 g (65%) of a colorless solid of 21 of m.p. >230◦C (decomp.). 1H-
NMR (DMSO-d6): 12.78 (s, H-N(8)); 8.17 (s, H-C(2)); 7.71 (bs, 1H, NH2);
7.50 (bs, 1H, NH2); 3.74 (s, 2H, CH2CO); 3.10 (q, 2H, OCH2CH3); 1,16
(t, 3H, CH3CH2). Anal. For C10H11N5O3 (249.2) Calcd: C 48.19, H 4.45, N
28.10. Found: C 48.14, H 4.47, N 27.73.
4-Amino-2,6-dimethyl-7(8H)pteridone (22)
a) To a solution of 18 (0.5 g, 3.6 mmol) in AcOH (10 ml) was added
ethyl pyruvate (1.0 ml, 9 mmol) and then heated under reflux for 1 hour.
After cooling the precipitate was collected, recrystallized from DMF/H2O
(1:1, 90 ml) with charcoal and dried at 60◦C to give 0.372 g (54%) of a
colorless solid of 22 of m.p. >300◦C (decomp.).
b) A solution of 23 (1.31 g, 5 mmol) in 1 N HCl (50 ml) was heated
in an oilbath to 120◦C for 1.5 hours. Charcoal was added, filtered hot, and
the filtrate was buffered by NaHCO3 to pH 5. The precipitate was collected
and recrystallized from DMF/H2O (1:1, 160 ml) to give 0.64 g (65%) of a
colorless solid of 22 of m.p. >360◦C (decomp.). 1H-NMR (DMSO-d6): 12.43
(s, H-N(8)); 7.42 (bs, 1H, NH2); 7.32 (bs, 1H, NH2); 2.34 (s, 6H, H3C-C(6),
H3C-C(2)). Anal. For C8H9N5O (191.2) Calcd: C 50.26, H 4.74, N 36.63.
Found: C 50.15, H 4.82, N 36.35.
4-Amino-6-ethoxycarbonylmethyl-2-methyl-7(8H)pteridone (23)
A solution of 18 (3.0 g, 22 mmol) in AcOH (20 ml) was treated with
sodium diethyl oxalylacetate (5.09 g, 22 mmol) in an oilbath at 100◦C for 2
hours. The suspension was diluted with H2O (40 ml), heated with charcoal,
and filtered hot. After cooling the precipitate was collected, dried to give
3.72 g (64%) of a colorless solid of 23 of m.p. >230◦C (decomp.). 1H-NMR
(DMSO-d6): 12.66 (s, H-N(8)); 7.65 (bs, 1H, NH2); 7.35 (bs, 1H, NH2); 3.71
(s, 2H, CH2CO); 3.10 (q, 2H, OCH2CH3); 2.33 (s, H3C-C(2)); 1,16 (t, 3H,
CH3CH2). Anal. For C11H13N5O3 (263.3) Calcd: C 50.19, H 4.98, N 26.60.
Found: C 49.97, H 5.00, N 26.90.
4-Amino-8-(3,5-di-O-4-chlorobenzoyl-2-deoxy-ß-D-erythro-
pentofuranosyl)-7(8H)pteridone (27) and α-Anomer 34
A suspension of 6 (1.63 g, 10 mmol) in dry CH3CN (100 ml) was
treated at room temperature with DBU (1.49 ml, 10 mmol) for 30 minutes.
Then 3,5-di-O-4-chlorobenzoyl-2-deoxy-ß-D-erythro-pentofuranosyl chloride
(25) (4.73 g, 11 mmol) was added and stirring continued for 2.5 hours.
The mixture was evaporated to dryness, the residue d´ıssolved in CH2Cl2
(100 ml), and then extracted twice with H2O (40 ml) and saturated NaCl

4-Amino-7(8H)pteridinone-N8-nucleosides
567
solution (40 ml). The organic layer was separated, dried over Na2SO4,
evaporated, the residue dissolved in little toluene, and put onto a silica-gel
column (20 × 5 cm). Chromatography with toluene/EtOAc (2:1, 1.5 l) gave
a main fraction of 2.28 g (41%) of the a/ß-mixture (1:5).
Fractional crystallization from CHCl3 (25 ml) and MeOH (15 ml) gave
as a first fraction 1.89 g (34%) of 27 as colorless crystals of m.p. 210–211◦C.
From the filtrate were obtained 0.28 g (5%) of 34 as colorless crystals of m.p.
178–180◦C.
1
27: H-NMR (DMSO-d6): 8.26 (s, H-C(2)); 8.00 (s, H-C(6)); 7.78–7.98
(m, 6H, NH2, 4 arom. H); 7,53 (d, 2H, arom. H); 7.45 (d, 2H, arom. H); 7.27
(m, H-C(1ꢁ)); 5.87 (m, H-C(3ꢁ)); 4.68 (m, H-C(4ꢁ)); 4.48 (m, 2 H-C(5ꢁ)); 3.21
(m, Hß-C(2ꢁ)); 2.55 (m, Hα-C(2ꢁ)). Anal. For C25H19Cl2N5O6 (556.4) Calcd:
C 53.97, H 3.44, N 12.59. Found: C 53.66, H 3.53, N 12.31.
1
34: H-NMR (DMSO-d6): 7.95 (m, 5H, H-C(6), 4 arom. H); 7.83 (bs,
NH2); 7.59 (d, 2H, arom. H); 7.53 (d, 2H, arom. H); 7.27 (m, H-C(1ꢁ)); 5.69
(m, H-C(3ꢁ)); 5.06 (m, H-C(4ꢁ)); 4.52 (m, 2 H-C(5ꢁ)); 2.92 (m, Hß-C(2ꢁ), Hα-
C(2ꢁ)). Anal. For C25H19Cl2N5O6 (556.4) Calcd: C 53.97, H 3.44, N 12.59.
Found: C 53.87, H 3.53, N 12.54.
4-Amino-2-phenyl-8-(3,5-di-O-toluoyl-2-deoxy-ß-D-erythro-
pentofuranosyl)-7(8H)pteridone (28)
a) A suspension of 12 (4.5 g, 19 mmol) in dry CH3CN (250 ml) was
treated with DBU (2.8 ml, 19 mmol) at room temperature for 30 minutes,
then 26 (8.04 g, 2.1 mmol) was added and stirring was continued for 2
hours. The dark reaction solution was evaporated in vacuum, the residue
dissolved in CH2Cl2 (150 ml), extracted twice with H2O (60 ml) and then
the organic layer dried over Na2SO4. After evaporation the residue was
dissolved in little toluene, put on a silica-gel column (15 × 5 cm) and eluted
by toluene/EtOAc (9:1, 1.2 l). The main fraction was collected, evaporated
and the residue recrystallized from CHCl3/MeOH to give 5.5 g (49%) of a
colorless solid of 28 of m.p. 196–198◦C.
b) A suspension of 12 (0.12 g, 0.5 mmol) in dry DMF (10 ml) and
1,2-dimethoxyethane 80.1 ml) was treated with KOH (56 mg, 1 mmol) to
achieve solution. Little KOH was filtered of and to the filtrate, 26 (0.233 g,
0.6 mmol) was added. After stirring at room temperature for 2 hours, the
soln was evaporated, the residue dissolved in CH2Cl2 (5 ml) and the solution
put onto a preparative silica-gel plate (40 × 20 ml) for chromatography with
toluene/EtOAc (7:3). The main band (Rf 0.50) was cut out, eluted with
CHCl3(MeOH (2:1, 20 ml) to give after drying in vacuum 0.165 g (52%)
of a colorless solid of 28 of m.p. 196–198◦C. 1H-NMR (DMSO-d6): 8.40 (m,
2H, arom. H); 7.99 (s, H-C(6)); 7.85 (m, 6H, NH2, 4 arom. H); 7.68 (m,
H-C(1ꢁ)); 7.49 (m, 3H, arom H); 7.34 (d, 2 arom. H); 7,21 (d, 2 arom.
H); 5.89 (m, H-C(3ꢁ)); 4.49–4.66 (m, H-C(4ꢁ), H-C(5ꢁ)); 3.21 (m, Hß-C(2ꢁ));

568
O. Jungmann and W. Pfleiderer
2.39 (m, Hα-C(2ꢁ)); 2.31 (s, 2 CH3). Anal. For C33H29N5O6 (591.6) Calcd: C
67.00, H 4.94, N 11.84. Found: C 67.09, H 4.95, N 11.90.
4-Amino-2-phenyl-8-(3,5-di-O-(4-chlorobenzoyl)-
2-deoxy-ß-D-erythro-pentofuranosyl)-7(8H)pteridone (29)
Analogous to the preceding procedure a) with 12 (4.5 g, 19 mmol) and
25 (8.2 g, 19 mmol) to give 6.0 g (50%) of colorless crystals of 29 of m.p.
1
>120◦C (slow decomp.). H-NMR (DMSO-d6): 8.38 (m, 3H, 2 arom. H,
H-C(6)); 7.89 (dd, H-C(1ꢁ)); 7.85 (2d, 6H, NH2, 4 arom. H); 7.61 (m, 2
arom. H); 7.53 (m, 5H, arom H); 5.90 (m, H-C(3ꢁ)); 4.54–4.65 (m, H-C(4ꢁ),
H-C(5ꢁ)); 3.21 (m, Hß-C(2ꢁ)); 2.40 (s, CH3); 2.33 (s, CH3); 2.20 (m, Hα-
C(2ꢁ)). Anal. For C31H23N5O6 (632.5) Calcd: C 58.87, H 3.67, N 11.07.
Found: C 58.79, H 3.65, N 11.00.
4-Amino-6-phenyl-8-(3,5-di-O-(4-chlorobenzoyl)-
2-deoxy-ß-D-erythro-pentofuranosyl)-7(8H)pteridone (30)
A suspension of 14 (0.5 g, 2.1 mmol) in dry CH3CN (15 ml) was treated
with DBU (313 µl, 2.1 mmol) at room temperature for 30 minutes, then
25 (1.1 g, 2.5 mmol) was added and stirring was continued for 1 hour. The
solution was evaporated in vacuum, the residue dissolved in CH2Cl2 (50 ml),
extracted twice with H2O (20 ml), and then the organic phase was dried over
Na2SO4. After evaporation the residue was dissolved in little toluene, put on
a silica-gel column (8 × 2.5 cm), and eluted by toluene/EtOAc (3:1, 250
ml). The main fraction was collected and evaporated to give 0.6 g (45%) of
1
a yellowish amorphous solid of 30. H-NMR (DMSO-d6): 8.34 (m, 2 arom.
H); 8.29 (s, H-C(6)); 7.93 (m, 6H, NH2, 4 arom. H); 7.42–7.63 (m, 8H,
NH2, H-C(1ꢁ), 6 arom. H); 5.98 (m, H-C(3ꢁ)); 4.72 (m, H-C(4ꢁ)); 4.56 (m,
2 H-C(5ꢁ)); 3.25 (m, Hß-C(2ꢁ)); 2.59 (m, Hα-C(2ꢁ)). Anal. For C31H23N5O6
(632.5) Calcd: C 58.87, H 3.67, N 11.07. Found: C 58.56, H 3.80, N 11.13.
4-Amino-2,6-diphenyl-8-(3,5-di-O-(4-chlorobenzoyl)-
2-deoxy-ß-D-erythro-pentofuranosyl)-7(8H)pteridone (31)
A suspension of 15 (0.5 g, 1.6 mmol) in dry CH3CN (25 ml) was treated
with DBU (240 µl, 2.1 mmol) at room temperature for 30 minutes, then 25
(0.82 g, 1.9 mmol) added and stirring was continued for 30 minutes. The
resulting precipitate was collected and recrystallized from CHCl3/MeOH
(2:1, 45 ml) to give 0.61 g (54%) of yellow crystals of 31 of m.p. 224–226◦C.
1H-NMR (DMSO-d6): 8.41 (m, 4 arom. H); 7.93 (2d, 6H, NH2, 4 arom. H);
7.75 (m, H-C(1ꢁ)); 7.62 (m, 2 arom. H); 7.50 (m, 4 arom. H); 6.04 (m, H-
C(3ꢁ)); 4.75 (m, H-C(4ꢁ)); 4.61 (m, 2 H-C(5ꢁ)); 3.31 (m, Hß-C(2ꢁ)); 2.69 (m,

4-Amino-7(8H)pteridinone-N8-nucleosides
569
1
Hα-C(2ꢁ)). H-NMR (CDCl3): 8.41 (m, 2 arom. H); 8.18 (m, 2 arom. H);
7.97 (2d, 4H, pClbz); 7.81 (m, H-C(1ꢁ)); 7.47 (m, 8H, arom. H); 7.23 (d,2H,
pClbz); 6.12 (m, 3H, NH2, H-C(3ꢁ)); 4.83 (m, H-C(4ꢁ)); 4.73 (m, 1H, H-
C(5ꢁ)); 4.57 (m, 1H, H-C(5ꢁ)); 3.45 (m, Hß-C(2ꢁ)); 2.62 (m, Hα-C(2ꢁ)). Anal.
For C37H27Cl2N5O6 (708.6) Calcd: C 62.72, H 3.84, N 9.88. Found: C 62.62,
H 3.88, N 9.81.
4-Amino-6-methyl-8-(3,5-di-O-(4-chlorobenzoyl)-
2-deoxy-ß-D-erythro-pentofuranosyl)-7(8H)pteridone (32)
and α-Anomer 35
A suspension of 20 (1.54 g, 9 mmol) in dry CH3CN (100 ml) was treated
with DBU (1.34 ml, 9 mmol) at room temperature for 30 minutes, then
25 (4.46 g, 10.8 mmol) was added and stirring continued for 2 hours. It
was evaporated, the residue dissolved in CH2Cl2 (60 ml), extracted twice
with saturated NaCl solution (30 ml) and after separation, the organic layer
was dried over Na2SO4. After another evaporation the crude product was
dissolved in toluene (10 ml) and put onto a silica-gel column (11 × 5 cm)
for chromatography with toluene/EtOAc (2:1, 600 ml) followed by (1:1,
400 ml). The product fractions were evaporated and the residue crystallized
from CHCl3/MeOH to give 0.85 g (17%) of 32, 0.34 g (7%) of 35 and 1.71 g
(33%) of the anomeric mixture 1:1.
1
32: Colorless crystals of m.p. 187–189◦C. H-NMR (DMSO-d6): 8.22 (s,
H-C(2)); 7.93 (2d, 4 arom. H); 7.79 (bs, NH2); 7.59 (d, 2 arom. H); 7.51 (d,
2 arom. H); 7.34 (m, H-C(1ꢁ)); 5.94 (m, H-C(3ꢁ)); 4.69 (m, H-C(4ꢁ)); 4.53
(m, 2 H-C(5ꢁ)); 3.18 (m, Hß-C(2ꢁ)); 2.55 (m, Hα-C(2ꢁ)); 2.38 (s, H3C-C(6)).
Anal. For C26H21Cl2N5O6 (570.4) Calcd: C 54.75, H 3.71, N 12.28. Found:
C 54.52, H 3.80, N 12.28.
1
35: Colorless crystals of m.p. 135–136◦C. H-NMR (DMSO-d6): 8.23 (s,
H-C(2)); 7.95 (2d, 4 arom. H); 7.70 (bs, NH2); 7.59 (d, 2 arom. H); 7.52 (d,
2 arom. H); 7.29 (m, H-C(1ꢁ)); 5.64 (m, H-C(3ꢁ)); 5.08 (m, H-C(4ꢁ)); 4.52
(m, 2 H-C(5ꢁ)); 2.92 (m, 2H, Hß-C(2ꢁ), Hα-C(2ꢁ)); 2.39 (s, H3C-C(6)). Anal.
For C26H21Cl2N5O6 × 0.5 H2O (579.4) Calcd: C 53.90, H 3.83, N 12.09.
Found: C 54.15, H 3.85, N 12.06.
4-Amino-2,6-dimethyl-8-(3,5-di-O-(4-chlorobenzoyl)-
2-deoxy-ß-D-erythro-pentofuranosyl)-7(8H)pteridone (33)
A suspension of 22 (0.79 g, 4.1 mmol) in dry CH3CN (30 ml) was treated
with DBU (615 µl, 4.1 mmol) at room temperature for 15 minutes, then
25 (2.1 g, 5 mmol) added, and stirring was continued for 2 hours. The
precipitate was collected and recrystallized from CHCl3/MeOH (1:2, 45 ml)
to give 0.96 g (40%) of colorless crystals of 33 of m.p. 218–220◦C (decomp.).
The filtrate yielded 0.39 g (16%) of the anomeric mixture 33/36 (2:1).

570
O. Jungmann and W. Pfleiderer
1H-NMR (DMSO-d6): 7.96 (d, 2 arom. H); 7.89 (d, 2 arom. H); 7.50 (d,
2 arom. H); 7.42 (bs, NH2); 7.30 (m, H-C(1ꢁ)); 6.00 (m, H-C(3ꢁ)); 4.69 (m,
H-C(4ꢁ)); 4.53 (m, 2 HC(5ꢁ)); 3.17 (m, Hß-C(2ꢁ)); 2.57 (m, Hα-C(2ꢁ)); 2.40
(s, H3C-C(6)); 2.36 (s, H3C-C(2)). Anal. For C27H23Cl2N5O6 (584.4) Calcd:
C 55.49, H 3.97, N 11.98. Found:C 55.57, H 4.09, N 11.53.
4-Amino-8-(2-deoxy-ß-D-erythro-pentofuranosyl)-7(8H)pteridone
(37)
NaOCH3 (0.22 g, 4 mmol) was dissolved in dry MeOH (80 ml) and then
27 (2.24 g, 4 mmol) was added and the mixture stirred for 2 days at room
temperature. The suspension was neutralized by AcOH and the precipitate
was collected. Drying in vacuum at 80◦C yielded 0.96 g (86%) of a colorless
1
powder of 37 of m.p. >180◦C (decomp.). H-NMR (DMSO-d6): 8.24 (s, H-
C(2)); 7.95 (s, H-C(6)); 7.83 (bs, NH2); 7.12 (m, H-C(1ꢁ)); 5.20 (d, HO-
C(3ꢁ)); 4.71 (d, HO-C(5ꢁ)); 4.43 (m, H-C(3ꢁ)); 3.76 (m, H-C(4ꢁ)); 3.65 (m, 1
H-C(5ꢁ)); 3.54 (m, 1 H-C(5ꢁ)); 2.89 (m, Hß-C(2ꢁ)); 2.02 (m, Hα-C(2ꢁ)). Anal.
For C11H13Cl2N5O4 (279.3) Calcd: C 47.31, H 4.69, N 25.08. Found: C 47.31,
H 4.72, N 25.05.
4-Amino-8-(2-deoxy-ß-D-erythro-pentofuranosyl)-2-phenyl-
7(8H)pteridone (38)
Either 28 (0.592 g, 1 mmol) or 29 (0.632 g, 1 mmol) was stirred in dry
MeOH (20 ml) in presence of NaOCH3 (54 mg, 1 mmol) for 2 days at room
temperature. The suspension was neutralized by AcOH, the precipitate was
collected and dried in vacuum at 80◦C to give 0.306 g (86%) of a colorless
1
powder of 38 of m.p. >260◦C (decomp.). H-NMR (DMSO-d6): 8.35 (m,
2 arom. H); 7.93 (s, H-C(6)); 7.78 + 7.87 (2 bs, NH2); 7.52 (m, 3 arom.
H); 7.44 (dd, H-C(1ꢁ)); 5.21 (d, HO-C(3ꢁ)); 4.62 (d, HO-C(5ꢁ)); 4.46 (m,
H-C(3ꢁ)); 3.81 (m, H-C(4ꢁ)); 3.67 (m, 1 H-C(5ꢁ)); 3.52 (m, 1 H-C(5ꢁ)); 2.94
(m, Hß-C(2ꢁ)); 2.11 (m, Hα-C(2ꢁ)). Anal. For C17H17N5O4 × H2O (364.4)
Calcd: C 56.04, H 4.98, N 19.22. Found: C 55.82, H 4.88, N 18.80.
4-Amino-8-(2-deoxy-ß-D-erythro-pentofuranosyl)-6-phenyl-
7(8H)pteridone (39)
A suspension of 4-N,N-dimethylaminomethyleneimino-6-phenyl-8-[(3,5-
di-O-(4-chlorobenzoyl) -2 -deoxy -ß -D-erythro -pentofuranosyl] -7 (8H) pteri-
done (51) (0.65 g, 1 mmol) in MeOH was treated with K2CO3 (70 mg,
0.5 mmol) and conc. NH3 (0.7 ml) under stirring for 2 days at room
temperature. It was evaporated to half of the volumn, then neutralized
by AcOH, and the precipiate was collected. Recrystallization from MeOH
gave 0.3.16 g (89%) of yellow crystals of 39 of m.p. >165◦C (decomp.).

4-Amino-7(8H)pteridinone-N8-nucleosides
571
1H-NMR (DMSO-d6): 8.32 (m, 2 arom. H); 8.20 (s, H-C(2)); 7.81 + 7.88 (2
bs, NH2); 7.47 (m, 3 arom. H); 7.22 (dd, H-C(1ꢁ)); 5.17 (d, HO-C(3ꢁ)); 4.71
(d, HO-C(5ꢁ)); 4.48 (m, H-C(3ꢁ)); 3.79 (m, H-C(4ꢁ)); 3.69 (m, 1 H-C(5ꢁ));
3.55 (m, 1 H-C(5ꢁ)); 2.95 (m, Hß-C(2ꢁ)); 2.06 (m, Hα-C(2ꢁ)). Anal. For
C17H17N5O4 (355.4) Calcd: C 57.46, H 4.82, N 19.71. Found: C 57.30, H
4.91, N 19.48.
4-Amino-8-(2-deoxy-ß-D-erythro-pentofuranosyl)-2,6-diphenyl-
7(8H)pteridone (40)
To a solution of NaOCH3 (19 mg, 0.35 mmol) in dry MeOH (15 ml) was
added 31 (0.25 g, 0.35 mmol) and the mixture was stirred for 12 hours. It
was neutralized by AcOH, the precipitate was collected, and dried in vacuum
at 80◦C to give 0.145 g (96%) of a yellow powder of 40 of m.p. >220◦C
(decomp.). 1H-NMR (DMSO-d6): 8.39 (m, 4 arom. H); 7.90 (bs, NH2); 7.50
(m, 7H, H-C(1ꢁ), 6 arom. H); 5.24 (d, HO-C(3ꢁ)); 4.65 (d, HO-C(5ꢁ)); 4.51
(m, H-C(3ꢁ)); 3.82 (m, H-C(4ꢁ)); 3.65 (m, 1 H-C(5ꢁ)); 3.56 (m, 1 H-C(5ꢁ));
2.98 (m, Hß-C(2ꢁ)); 2.17 (m, Hα-C(2ꢁ)). Anal. For C23H21N5O4 (431.5)
Calcd: C 64.03, H 4.91, N 16.23. Found: C 63.91, H 5.05, N 15.90.
4-Amino-8-(2-deoxy-ß-D-erythro-pentofuranosyl)-6-methyl-
7(8H)pteridone (41)
a) To a solution of sodium (20 mg, 0.88 mmol) in dry MeOH (20 ml)
was added 32 (0.5 g, 0.88 mmol) and the mixture was stirred for 12 hours.
It was neutralized by AcOH, concentrated to 10 ml, and the precipitate was
collected and dried in vacuum at 80◦C to give 0.16 g (62%) of a colorless
powder of 41 of m.p. >190◦C (decomp.).
b) A suspension of 4-N,N-dimethylaminomethyleneimino-6-methyl-8-
[(3,5-di-O-(4-chlorobenzoyl)-2-deoxy -ß-D -erythro -pentofuranosyl]- 7(8H)
pteridone (55) (2.0 g, 3.2 mmol) in MeOH was treated with K2CO3 (0.44
g, 3.2 mmol) and conc. NH3 (5 ml) under stirring for 2 days at room
temperature. It was evaporated to half of the volumn, then neutralized by
AcOH and the precipiate was collected and dried in vacuum at 80◦C to
give 0.76 g (81%) of colorless crystals of 41 of m.p. >190◦C (decomp.).
1H-NMR (DMSO-d6): 8.20 (s, H-C(2));); 7.52+7.70 (2 bs, NH2); 7.15 (dd,
H-C(1ꢁ)); 5.17 (d, HO-C(3ꢁ)); 4.72 (d, HO-C(5ꢁ)); 4.44 (m, H-C(3ꢁ)); 3.67
(m, H-C(4ꢁ)); 3.60 (m, 1 H-C(5ꢁ)); 3.54 (m, 1 H-C(5ꢁ)); 2.88 (m, Hß-C(2ꢁ));
2.36 (s, H3C-C(6)); 2.01 (m, Hα-C(2ꢁ)). Anal. For C12H15N5O4 (293.3)
Calcd: C 49.13, H 5.16, N 23.88. Found: C 49.13, H 5.03, N 23.73.

572
O. Jungmann and W. Pfleiderer
4-Amino-8-(2-deoxy-ß-D-erythro-pentofuranosyl)-2,6-dimethyl-
7(8H)pteridone (42)
a) To a solution of sodium (30 mg, 1.33 mmol) in dry MeOH (20 ml) was
added 33 (0.78 g, 1.33 mmol) and the mixture was stirred for 12 hours. It was
neutralized by AcOH, concentrated to 10 ml, the precipitate was collected,
washed with MeOH, and dried in vacuum at 80◦C to give 0.38 g (93%) of
1
a colorless solid of 42 of m.p. >180◦C (decomp.). H-NMR (DMSO-d6):);
7.38 + 7.57 (2 bs, NH2); 7.14 (dd, H-C(1ꢁ)); 5.16 (d, HO-C(3ꢁ)); 4.66 (d,
HO-C(5ꢁ)); 4.45 (m, H-C(3ꢁ)); 3.74 (m, H-C(4ꢁ)); 3.65 (m, 1 H-C(5ꢁ)); 3.53
(m, 1 H-C(5ꢁ)); 2.88 (m, Hß-C(2ꢁ)); 2.37 (s, H3C-C(6)); 2.34 (s, H3C-C(2));
1.99 (m, Hα-C(2ꢁ)). Anal. For C13H17N5O4 (307.3) Calcd: C 50.81, H 5.58,
N 22.79. Found: C 50.34, H 5.80, N 23.08.
4-N,N-Dimethylaminomethyleneimino-7(8H)pteridone (43)
A suspension of 4-amino-7(8H)-pteridone (6) (1.63 g, 10 mmol) in
dry DMF (20 ml) was treated with N,N-dimethylformamide-diethylacetal
(2.6 ml, 15 mmol) at 60◦C in an oilbath for 5 hours. After cooling, the
precipitate was collected, washed with EtOH and dried in vacuum at 80◦C.
The reaction filtrate was evaporated in vacuum to dryness and the residue
was recrystallized from EtOH to give a total of 1.99 g (91%) of a colorless
solid of 43 of m.p. 289–291◦C. 1H-NMR (DMSOd6): 12.78 (s, H-N(8)); 8.76
(s, N CH-N); 8.42 (s, H-C(2)); 8.04 (s, H-C(6)); 3.20 (s, 3H, NCH3Me); 3.12
(s. 3H, NCH3Me). Anal. For C9H10N6O (218.2) Calcd: C 49.54, H 5.62, N
38.51. Found: C 49.52, H 4.68, N 38.77.
4-N,N-Dimethylaminomethyleneimino-2-phenyl-7(8H)pteridone
(44)
Analogous to the preceding procedure with 12 (2.39 g, 10 mmol) to give
2.47 g (84%) of a colorless solid of 44 of m.p. 257–260◦C. Recrystallization
1
from isopropanol gave colorless crystals. H-NMR (DMSO-d6): 12.74 (s,
H-N(8)); 8.94 (s, N CH-N); 8.44 (m, 2 arom. H); 8.02 (s, H-C(6)); 7.51
(m, 3 arom. H); 3.33 (s, 3H, NCH3Me); 3.26, s. 3H, NCH3Me). Anal. For
C15H14N6O (294.3) Calcd: C 61.21, H 4.79, N 28.55. Found: C 61.12, H 4.86,
N 28.77.
4-N,N-Dimethylaminomethyleneimino-6-phenyl-7(8H)pteridone
(45)
Analogous to the preceding procedure with 14 (2.39 g, 10 mmol) to give
2.59 g (88%) of a colorless solid of 45 of m.p. 257–260◦C. Recrystallization
1
from EtOH gave colorless crystals. H-NMR (DMSOd6): 12.89 (s, H-N(8));
8.43 (s, N CH-N); 8.38 (s, H-C(2)); 8.26 (m, 2 arom. H); 7.48 (m, 3 arom.

4-Amino-7(8H)pteridinone-N8-nucleosides
573
H); 3.22 (s, 3H, NCH3Me); 3.17 (s. 3H, NCH3Me). Anal. For C15H14N6O
(294.3) Calcd: C 61.21, H 4.79, N 28.55. Found: C 60.88, H 5.00, N 28.15.
4-N,N-Dimethylaminomethyleneimino-2,6-diphenyl-
7(8H)pteridone (46)
Analogous to the preceding procedure with 15 (3.15 g, 10 mmol) to
give 3.14 g (85%) of a colorless solid of 46 of m.p. 269–270◦C. Recrystalliza-
1
tion from isopropanol gave colorless crystals. H-NMR (DMSO-d6): 12.89
(s, H-N(8)); 8.93 (s, N CH-N); 8.42 (m, 2 arom. H); 8.31 (m, 2 arom. H);
7.50 (m, 6 arom. H); 3.28 (s, 3H, NCH3Me); 3.21 (s. 3H, NCH3Me). Anal.
For C21H18N6O (370.4) Calcd: C 68.10, H 4.90, N 22.69. Found: C 67.86, H
4.98, N 22.86.
4-N,N-Dimethylaminomethyleneimino-6-methyl-7(8H)pteridone
(47)
A suspension of 19 (1.0 g, 5.6 mmol) in dry DMF (15 ml) was treated
with N,N-dimethylformamide-diethylacetal (1.45 ml, 8.4 mmol) at 60◦C
in an oilbath for 1.5 hours. After cooling, the precipitate was collected,
washed with EtOH and dried in vacuum at 80◦C. The reaction filtrate was
evaporated in vacuum to dryness, the residue was treated with ether and
dried to give a total of 1.13 g (87%) of a colorless solid of 47 of m.p. >220◦C
1
(decomp.). H-NMR (DMSO-d6): 12.82 (s, H-N(8)); 8.70 (s, N CH-N);
8.38 (s, H-C(2)); 3.20 (s, 3H, NCH3Me); 3.13 (s. 3H, NCH3Me); 2.38 (s,
H3C-C(6)). Anal. For C10H12N6O × 0.5 H2O (236.7) Calcd: C 50.73, H 5.32,
N 35.50. Found: C 50.56, H 5.39, N 35.09.
4-N,N-Dimethylaminomethyleneimino-2,6-dimethyl-
7(8H)pteridone (48)
A suspension of 22 (2.24 g, 11.7 mmol) in dry DMF (20 ml) was treated
with N,N-dimethylformamidediethylacetal (3.0 ml, 17.5 mmol) at room
temperature for 3 hours. The precipitate was collected, washed with EtOH
and dried in vacuum at 80◦C. The reaction filtrate was evaporated in vacuum
to dryness, the residue was treated with EtOH and ether and dried to give a
total of 2.59 g (90%) of a colorless solid of 48 of m.p. 220◦C (decomp.).
1H-NMR (DMSO-d6): 12.49 (s, H-N(8)); 8.61 (s, N CH-N); 3.18 (s, 3H,
NCH3Me); 3.11 (s. 3H, NCH3Me); 2.42 (s, H3CC(6)); 2.33 (s, H3C-C(2)).
Anal. For C11H14N6O (246.3) Calcd: C 53.65, H 5.73, N 34.13. Found: C
53.81, H 5.79, N 34.19.

574
O. Jungmann and W. Pfleiderer
4-N,N-Dimethylaminomethyleneimino-8-(3,5-di-O-4-
chlorobenzoyl- 2-deoxy-ß-D-erythro-pentofuranosyl)-
7(8H)pteridone (49)
A suspension of 4-N,N-dimethylaminomethyleneimino-7(8H)pteridone
(43) (2.18 g, 10 mmol) in dry CH3CN (150 ml) was treated with DBU
(1.49 ml, 10 mmol) and stirred at room temperature for 30 minutes. After
addition of 25 (4.73 g, 11 mmol) the mixture was stirred for another
2.5 hours, filtered, and the filtrate evaporated to dryness. The residue
was dissolved in CH2Cl2 (100 ml), extracted twice with H2O (40 ml),
the organic layer was separated, dried over Na2SO4, evaporated, and the
residue put onto a silica-gel column (20 × 5 cm) for chromatography with
n-hexane/acetone (1:1, 1.5 l). The first fraction (Rf 0.71) consisted of 27
(0.78 g, 14%) and the second fraction (Rf 0.45) gave after evaporation 1.28
1
g (21%) of 49 of m.p. 152–155◦C. H-NMR (DMSO-d6): 8.73 (s, N CHN);
8.51 (s, H-C(2)); 8.17 (s, H-C(6)); 7.45 (m, 4 arom. H); 7.29–7.48 (2 d,
5H, HC(1ꢁ), 4 arom. H); 5.99 (m, H-C(3ꢁ)); 4.77 (m, H-C(4ꢁ)); 4.68 (m,
H-C(5ꢁ)); 5.52 (m, H-C(5ꢁ)); 3.42 (m, Hß-C(2ꢁ)); 3.28 (s, N-CH3); 3.22 (s,
N-CH3); 2.50 (m, Hα-C(2ꢁ)). Anal. For C28H24Cl2N6O6 (611.4) Calcd: C
55.00, H 3.96, N 13.75. Found: C 54.86, H 3.92, N 13.92.
4-N,N-Dimethylaminomethyleneimino-2-phenyl-8-(3,5-di-O-
toluoyl -2-deoxy-ß-D-erythro-pentofuranosyl)-7(8H)pteridone
(50)
A suspension of 44 (1.0 g, 3.4 mmol) in dry CH3CN (60 ml) was treated
with DBU (506 µl, 3.4 mmol) and stirred at room temperature for 20
minutes. After addition of 26 (1.45 g, 3.7 mmol) the mixture was stirred for
another 1.5 hours, filtered, and the filtrate was evaporated to dryness. The
residue was dissolved in CH2Cl2 (100 ml), shaken twice with H2O (40 ml),
the organic layer was separated, dried over Na2SO4, evaporated, and the
residue put onto a silica-gel column (15 × 3 cm) for chromatography with
CH2Cl2/acetone (9:1, 750 ml). The first fraction consisted of 28 (0.663 g,
33%) and the second fraction (Rf 0.31) gave after evaporation 0.835 g
(38%) of 50. Recrystallization from CHCl3/MeOH gave 0.374 g (17%) of
1
yellowish crystals of of 50 of m.p. 171–173◦C. HNMR (DMSO-d6): 8.91 (s,
N CHN); 8.45 (m, 2 arom. H); 8.14 (s, H-C(6)); 7.93 (m, 4 arom. H);
7.80 (m, H-C(1ꢁ)); 7.46 (m, 3 arom. H); 7.23 (m, 2 arom. H); 7.12 (m, 2
arom. H); 5.99 (m, H-C(3ꢁ)); 4.60–4.76 (m, 3H, H-C(4ꢁ), H-C(5ꢁ)); 3.44 (m,
Hß-C(2ꢁ)); 3.31 (s, N-CH3); 3.26 (s, N-CH3); 2.33 (m, Hα-C(2ꢁ)). Anal. For
C36H34N6O6 (646.7) Calcd: C 66.86, H 5.30, N 13.00. Found: C 66.71, H
5.28, N 12.90.

4-Amino-7(8H)pteridinone-N8-nucleosides
575
4-N,N-Dimethylaminomethyleneimino-6-phenyl-8-(3,5-di-O-4-
chlorobenzoyl-2-deoxy-ß-D-erythro-pentofuranosyl)-
7(8H)pteridone (51)
A suspension of 45 (2.94 g, 10 mmol) in dry CH3CN (60 ml) was treated
with DBU (1.49 ml, 10 mmol) and stirred at room temperature for 20
minutes to give a clear solution. After addition of 25 (4.72 g, 11 mmol) the
reaction mixture was stirred for another 1 hour and the resulting precipitate
was collected, washed with ether, and dried in vacuum at 40◦C to give 4.13 g
1
(60%) of a yellow powder of 51 of m.p. 225–227◦C. H-NMR (DMSO-d6):
8.74 (s, N CHN); 8.54 (s, H-C(2)); 8.27 (m, 2 arom. H); 7.98 (m, 4 arom.
H); 7.61 (m, H-C(1ꢁ)); 7.44 (m, 3 arom. H); 7.26 (d, 2 arom. H); 7.12 (m,
2 arom. H); 6.12 (m, H-C(3ꢁ)); 4.82 (m, H-C(4ꢁ)); 4.75 (m, H-C(5ꢁ)); 4.53
(m, H-C(5ꢁ)); 3.46 (m, Hß-C(2ꢁ)); 3.31 (s, N-CH3); 3.22 (s, N-CH3); 2.55
(m, Hα-C(2ꢁ)). Anal. For C34H28Cl2N6O6 (687.5) Calcd: C 59.40, H 4.10, N
12.22. Found: C 59.35, H 4.14, N 11.97.
4-N,N-Dimethylaminomethyleneimino-2,6-diphenyl-8-(3,5-di-O-4-
chlorobenzoyl-2deoxy-ß-D-erythro-pentofuranosyl)-
7(8H)pteridone (52)
A suspension of 46 (3.7 g, 10 mmol) in dry CH3CN (80 ml) was treated
with DBU (1.49 ml, 10 mmol) and stirred at room temperature for 20
minutes to give a clear solution. After addition of 25 (4.72 g, 11 mmol) the
reaction mixture was stirred for another 1 hour, the resulting precipitate
was collected and recrystallized from CHCl3/MeOH and dried in vacuum
at 40◦C to give 4.2 g (55%) of a yellow powder of 52 of m.p. 225–227◦C.
1H-NMR (DMSO-d6): 8.90 (s, N CHN); 8.48 (m, 2 arom. H); 8.29 (m, 2
arom. H); 7.96 (m, 5H, H-C(1ꢁ), 4 arom. H); 7.45 (m, 8 arom. H); 7.23 (d,
2 arom. H); 6.15 (m, H-C(3ꢁ)); 4.58–4.81 (m, H-C(4ꢁ), 2 H-C(5ꢁ)); 3.45 (m,
Hß-C(2ꢁ)); 3.32 (s, N-CH3); 3.25 (s, N-CH3); 2.58 (m, Hα-C(2ꢁ)). Anal. For
C40H32Cl2N6O6 (763.6) Calcd: C 62.91, H 4.22, N 11.01. Found: C 62.92, H
4.29, N 10.69.
4-N,N-Dimethylaminomethyleneimino-2,6-diphenyl-8-(3,5-di-O-
toluoyl-2-deoxy-ß-D-erythro-pentofuranosyl)-7(8H)pteridone
(53)
A suspension of 46 (3.7 g, 10 mmol) in dry CH3CN (80 ml) was
treated with DBU (1.49 ml, 10 mmol) and stirred at room temperature for
20 minutes to give a clear solution. After addition of 26 (4.28 g, 11 mmol)
the reaction mixture was stirred for another 1 hour, the resulting precipitate
was collected and recrystallized from CHCl3/MeOH and dried in vacuum
at 40◦C to give 5.17 g (71%) of a yellow powder of 53 of m.p. 218–220◦C.

576
O. Jungmann and W. Pfleiderer
From the filtrate an α/ß-anomeric mixture (53/54) 1.52 g (21%) could be
1
isolate but all attempts to get pure 54 failed. H-NMR (DMSO-d6): 8.89 (s,
N CHN); 8.48 (m, 2 arom. H); 8.33 (m, 2 arom. H); 7.93 (m, H-C(1ꢁ)); 7.45
(m, 6 arom. H); 7.23 (d, 2 arom. H); 7.08 (d, 2 arom. H); 6.11 (m, H-C(3ꢁ));
4.60–4.85 (m, H-C(4ꢁ), 2 H-C(5ꢁ)); 3.46 (m, HßC(2ꢁ)); 3.32 (s, N-CH3); 3.25
(s, N-CH3); 2.60 (m, Hα-C(2ꢁ)); 2.41 (s, H3C-C); 2.32 (s, H3CC). Anal. For
C42H38N6O6 (722.8) Calcd: C 69.79, H 5.30, N 11.63. Found: C 69.51, H
5.30, N 11.42.
4-N,N-Dimethylaminomethyleneimino-6-methyl-8-(3,5-di-O-4-
chlorobenzoyl-2-deoxy-ß-D-erythro-pentofuranosyl)-
7(8H)pteridone (55)
A suspension of 47 (2.16 g, 9.3 mmol) in dry CH3CN (40 ml) was treated
with DBU (1.39 ml, 9.3 mmol) and stirred at room temperature for 20
minutes. After addition of 25 (4.8 g, 11.1 mmol) the reaction mixture was
stirred for another 1 hour, the precipitate was filtered off and recrystallized
from CHCl3/MeOH (1:1, 30 ml) to give 2.2 g (38%) and from the filtrate
0.44 g (7%) of colorless crystals of 55 of m.p. 171–174◦C. 1H-NMR (CDCl3):
8.75 (s, N CHN); 8.52 (s, H-C(2)); 7.99 (2 d, 4 arom. H); 7.52 (dd, H-C(1ꢁ));
7.43 (d, 2 arom. H); 7.34 (d, 2 arom. H); 6.08 (m, H-C(3ꢁ)); 4.68 (m,
1 H-C(5ꢁ)); 4.58 (m, H-C(4ꢁ)); 3.42 (m, Hß-C(2ꢁ)); 3.31 (s, N-CH3); 3.23
(s, N-CH3); 2.58 (s, H3C-C(6)); 2.53 (m, Hα-C(2ꢁ)). Anal. For C36H34N6O6
(646.7) Calcd: C 66.86, H 5.30, N 13.00. Found: C 66.71, H 5.28, N 12.90.
4-Amino-8-(2,3,5-tri-O-benzoyl-ß-D-erythro-pentofuranosyl)-
7(8H)pteridone (57)
a) A suspension of compound 6 (1.0 g, 6.1 mmol) in dry CH3CN (100
ml) and dry DMF (50 ml) was treated with DBU (0.9 ml, 6.1 mmol) and
stirred at room temperature for 15 minutes. After addition of 2,3,5-tri-
O-benzoyl-1-bromo-α-D-erythro-pentofuranose (56) (3.86 g, 7.4 mmol), the
reaction mixture was stirred for another 2.5 hours, then evaporated to
dryness, the residue was dissolved in CH2Cl2 (50 ml), and extracted twice
with saturated NaCl solution (30 ml). The organic phase was separated,
dried over Na2SO4, evaporated again, and the residue dissolved in little
toluene and put onto to a silica-gel column (10 × 5 cm) for chromatography
with toluene/EtOAc(1:1, 500 ml) and followed by toluene/EtOAc (2:1, 500
ml). The main fraction was collected, evaporated and the solid recrystallized
from isopropanol to give 0.8 g (22%) of a colorless powder of 57 of m.p.
>105◦C (decomp.).
b) A mixture of compound 6 (1.64 g, 10 mmol) and a few crystals of
(NH4)2SO4 in HMDS (30 ml) was heated under reflux for 2 hours. The
excess of HMDS was evaporated in vacuum and the resulting oily mixture

4-Amino-7(8H)pteridinone-N8-nucleosides
577
(66) dissolved in dry CHCl3 (50 ml). After addition of 70 (5.05 g, 10 mmol)
followed by BF3-etherate (10 ml, 80 mmol), the reaction mixture was stirred
at room temperature for 12 hours. The soln was poured into H2O (100 ml),
neutralized with NaHCO3, the organic phase was separated and dried over
Na2SO4. It was again evaporated, the residue dissoloved in little toluene
and put onto a silica-gel column (12 × 5 cm) for chromatography with
toluene/EtOAc (3:1, 1.8 l). The product fraction eluted late, was evaporated
to give 4.2 g (69%) of a colorless foam of 57 of m.p. >105◦C (decomp.).
1H-NMR (DMSO-d6): 8.26 (s,HC(2)); 8.10 (s, H-C(6)); 7.92 (m, 6H, NH2,
4 arom. H); 7.81 (d, 2 arom. H); 7.61 (m, 3 arom. H); 7.39 (m, 6 arom.
H); 7.12 (bs, H-C(1ꢁ)); 6.31 (m, 2H, H-C(2ꢁ), H-C(3ꢁ)); 4.75 (m, 1 HC(5ꢁ),
H-C(4ꢁ)); 4.58 (m, 1 H-C(5ꢁ)). Anal. For C32H25N5O8 (607.6) Calcd: C 63.26,
H 4.14, N 11.53. Found: C 63.18, H 4.19, N 11.39.
4-Amino-2-phenyl-8-(2,3,5-tri-O-benzoyl-ß-D-erythro-
pentofuranosyl)-7(8H)pteridone (58)
a) A suspension of 12 (1.0 g, 4.24 mmol) in dry CH3CN (80 ml) was
treated with DBU (0.62 ml, 6.1 mmol) and stirred at room temperature
for 30 minutes. After addition of 2,3,5-tri-Obenzoyl-1-bromo-α-D-erythro-
pentofuranose (56) (3.62 g, 5.0 mmol), the reaction mixture was stirred
for another 2 hours, then evaporated to dryness, the residue was dissolved
in CH2Cl2 (50 ml) and extracted twice with saturated NaCl solution (30 ml).
The organic phase was separated, dried over Na2SO4, evaporated again, the
residue dissolved in toluene (15 ml) and put onto to a silica-gel column (7
× 5 cm) for chromatography with toluene/EtOAc(3:1, 600 ml). The main
fraction was collected, evaporated and the solid recrystallized from MeOH
(200 ml) to give 0.97 g (34%) of a colorless solid of 58 of m.p. 157–158◦C.
b) A mixture of 12 (2.37 g, 9.9 mmol) and a few crystals of (NH4)2SO4
was heated in hexamethyldisilazane (HMDS) (50 ml) under reflux and
exclusion of moisture for 5 hours. The HMDS was removed in vacuum and
the residue of 67 dissolved in dry CH2Cl2 (60 ml). Then compound 70 (5.0
g, 9.9 mmol) was added, followed by BF3-etherate (8.9 ml, 70 mmol) and the
mixture stirred for 3 hours at room temperature. The solution was poured
into H2O (120 ml), neutralized with NaHCO3 and extracted with CH2Cl2.
The organic phase was separated, dried over Na2SO4, filtered, evaporated
again, the residue dissolved in toluene (30 ml), and put onto a silica-gel
column (15 × 5 cm) for chromatography with toluene/EtOAc (3:1, 1000
ml). The main fraction was collected, evaporated, the residue dissolved in
CH2Cl2 (10 ml), and this solution was added dropwise under stirring into
MeOH (150 ml). Cooling over night in the icebox (−20◦C) yielded 3.48 g
(51%) of 58 and from the filtrate another 0.3 g (5%) of a colorless solid
1
of 58 of m.p. 156–158◦C. H-NMR (DMSO-d6): 8.32 (m, 2 arom. H); 8.08
(s, H-C(6)); 7.91 (m, 8H, NH2, 6 arom. H); 7.63 (m, 3 arom. H); 7.47 (m,

578
O. Jungmann and W. Pfleiderer
H-C(1ꢁ), 9 arom. H); 6.27 (m, 2H, H-C(2ꢁ), H-C(3ꢁ)); 4.84 (m, H-C(4ꢁ)); 4.72
(m, 1 H-C(5ꢁ)); 4.58 (m, 1 H-C(5ꢁ)). Anal. For C38H29N5O8 (683.7) Calcd:
C 66.76, H 4.28, N 10.24. Found: C 67.04, H 4.33, N 10.32.
4-Amino-2,6-diphenyl-8-(2,3,5-tri-O-benzoyl-ß-D-erythro-
pentofuranosyl)7(8H)pteridone (59)
a) A suspension of 15 (1.0 g, 3.17 mmol) in dry CH3CN (50
ml) was treated with DBU (0.47 ml, 3.17 mmol) and stirred at room
temperature for 30 minutes. After addition of 2,3,5-tri-O-benzoyl-1-bromo-
α-D-erythro-pentofuranose (56) (1.87 g, 3.49 mmol), the reaction mixture
was stirred for another 1 hour, the yellow precipitate was collected, heated
with CHCl3/MeOH (1:1, 100 ml) and the insoluble educt filtered off. On
cooling, yellow needles precipitated to give 0.795 g (33%) of 59 of m.p.
241–243◦C.
b) A mixture of 15 (2.1 g, 6.7 mmol) and a few crystals of (NH4)2SO4
was heated in hexamethyldisilazane (HMDS) (80 ml) under reflux and
exclusion of moisture for 24 hours. The HMDS was removed in vacuum and
the residue of 69 was dissolved in dry CH2Cl2 (100 ml). Then compound 70
(3.8 g, 7.5 mmol) was added, followed by BF3-etherate (20 ml, 160 mmol)
and the mixture stirred for 24 hours at room temperature. The soln was
evaporated to half of its volume, the precipitate was collected, the filtrate
was diluted with n-hexane (50 ml), and the second crop again collected.
The solids were combined and heated in CHCl3/MeOH (1:1, 200 ml), the
insoluble educt filtered off. Cooling over night in the icebox yielded 1.6 g
(31%) of yellow needles of 59 of m.p. 240–243◦C. 1H-NMR (DMSO-d6): 8.43
(m, 2 arom. H); 8.35 (m, 2 arom. H); 8.08 (s, H-C(6)); 7.97 (m, 6H, NH2,
4 arom. H); 7.86 (d, 2 arom. H); 7.63 (m, 4 arom. H); 7.47 (m, H-C(1ꢁ),
11 arom. H); 6.43 (m, 2H, H-C(2ꢁ), H-C(3ꢁ)); 4.84 (m, H-C(4ꢁ)); 4.78 (m,
1 H-C(5ꢁ)); 4.60 (m, 1 H-C(5ꢁ)). Anal. For C44H33N5O8 (759.8) Calcd: C
69.55, H 4.38, N 9.22. Found: C 69.62, H 4.49, N 9.22.
4-N,N-Dimethylaminomethyleneimino-6-phenyl-8-(2,3,5-tri-O-
benzoyl-ß-D-erythro-pentofuranosyl)-7(8H)pteridone (60)
A suspension of 45 (2.0 g, 6.8 mmol) in dry CH3CN (100 ml) was
treated with DBU (1.0 ml, 6.8 mmol) and stirred at room temperature for 15
minutes to give a clear solution. After addition of 56 (3.93 g, 7.5 mmol), the
reaction mixture was stirred for another 2 hours and then evaporated, The
residue was dissolved in CH2Cl2 ((50 ml), shaken twice with saturated NaCl
solution (30 ml), the organic phase was separated, dried over Na2SO4 and
again evaporated. The residue was dissolved in toluene (20 ml) and put onto
a silica-gel column (14 × 6 cm) for chromatography with toluene/EtOAc
(1:1, 800 ml) and followed by toluene/EtOAc (2:1, 1000 ml) eluting the
product fraction. Evaporation and drying in high vacuum gave 2.6 g (52%)