Elimination reactions on the di- and trimesylated derivatives of N3-benzyluridine

Sasaki, Tadashi; Minamoto, Katsumaro; Suzuki, Hideaki

doi:10.1021/jo00943a041

Cited by 32 publications

(8 citation statements)

References 9 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The basic conditions were mild enough not to degrade the carborane cage. While alkylation at other positions may generally be possible under these reaction conditions, it has not been reported in the literature, , and selective alkylation of the N-3 position was confirmed by a correlation of the 13 C NMR chemical shifts of 29 − 32 with those of 3-methylthymidine and 4- O -methylthymidine 3 …”

Section: Resultsmentioning

confidence: 90%

See 1 more Smart Citation

Synthesis of 5-(Carboranylalkylmercapto)-2‘-deoxyuridines and 3-(Carboranylalkyl)thymidines and Their Evaluation as Substrates for Human Thymidine Kinases 1 and 2

et al. 1999

View full text Add to dashboard Cite

Derivatives of thymidine containing o-carboranylalkyl groups at the N-3 position and derivatives of 2'-deoxyuridine containing o-carboranylalkylmercapto groups at the C-5 position were synthesized. The alkyl spacers consist of 4-8 methylene units. The synthesis of the former compounds required 3-4 reaction steps in up to 75% overall yield and that of the latter 9-10 reaction steps with significantly lower overall yield. Derivatives of thymidine substituted with carboranylalkyl substituents at the N-3 position and short spacers were phosphorylated by both recombinant and purified cytosolic thymidine kinase (TK1) to a relatively high degree. None of the tested 2'-deoxyuridine derivatives possessing carboranyl substituents at the C-5 position were phosphorylated by either recombinant or purified TK1. The amounts of phosphorylation product detected for some of the C-5-substituted nucleosides with recombinant mitochondrial thymidine kinase (TK2) were low but significant and decreased with increasing lengths of the alkyl spacer. The data obtained in this study do not seem to support the tether concept applied in the synthesis of the new C-5- and N-3-substituted carboranyl nucleosides intended to reduce possible steric interference in the binding of carboranyl nucleosides with deoxynucleoside kinases. Instead, it appeared that a closer proximity of the bulky carborane moiety to the nucleoside scaffold resulted in better substrate characteristics.

show abstract

Section: Resultsmentioning

confidence: 90%

“…General Procedure for the N-3 Alkylation of Thd. Adapting a procedure described by Sasaki et al and Yamamoto et al, , Thd (1 equiv), K 2 CO 3 (2 equiv), and the corresponding alkylcarboranyl tosylates (1.1 equiv) were combined in 10 mL of anhydrous DMF/acetone (1/1). The mixtures were heated to 50 °C and stirred for 1−2 days.…”

Section: Methodsmentioning

confidence: 99%

Synthesis of 5-(Carboranylalkylmercapto)-2‘-deoxyuridines and 3-(Carboranylalkyl)thymidines and Their Evaluation as Substrates for Human Thymidine Kinases 1 and 2

et al. 1999

View full text Add to dashboard Cite

show abstract

“…Thus, when 15b (R = Ms or Ts) were treated with NaH in THF, mixtures of several unidentified products appeared. The 13 C-NMR spectra of those mixtures revealed the presence of several carbonyl signals around δ 206 …”

Section: Resultsmentioning

confidence: 99%

Synthesis of Purine and Pyrimidine 3‘-Amino-3‘-deoxy- and 3‘-Amino-2‘,3‘-dideoxyxylonucleosides

1996

View full text Add to dashboard Cite

A general procedure to obtain the 3'-aminoxylonucleosides 13a,b and 17a,b is presented. The synthetic scheme is based on the 5' directed intramolecular nucleophilic substitution at the 3'-activated position of the nucleoside. The approach of the incoming group to this position takes place regio- and stereoselectively from the most hindered face of the nucleoside. The methodology presented is applicable to ribonucleosides and 2'-deoxyribonucleosides, regardless of their nitrogenated base.

show abstract

“…17) Briefly, uridine (2 mmol) was dissolved in dimethylsulfoxide (DMSO) (3 ml) and acetone (3 ml) and was reacted with halogenated alkyls (3 mmol) in the presence of a base (K 2 CO 3 3 mmol). The product was purified by silica gel column chromatography with a solvent system of chloroform-ethyl acetate-methanol (5 : 4 : 1).…”

Section: Synthesis Of N 3 -Substituted Uridine and Related Pyrimidinementioning

confidence: 99%

“…6 d), o-, mand p-xylyl (1-6 e-g), and phenacyl (1-4 h) substituted pyrimidine nucleosides were prepared according to the method of previously reported. [6][7][8][9][10][11][12][13][14][15][16][17] Other N 3 -substituted compounds also synthesized by the method of above mentioned. The analytical data of the novel derivatives in the present study prepared were as follows: 2H, m, 3Ј-H, 4Ј-H (3H, m, NCH 2 , 4Ј-H), 5.98-6.02 (1H, m, 1Ј-H), 7.28-7.38 (3H, m, C 6 H 3 Evaluation of Antinociceptive Effect Male std-ddY mice weighing 22 to 25 g were obtained from Sankyo Laboratories (Shizuoka, Japan).…”

Section: Synthesis Of N 3 -Substituted Uridine and Related Pyrimidinementioning

confidence: 99%

Synthesis of N3-Substituted Uridine and Related Pyrimidine Nucleosides and Their Antinociceptive Effects in Mice

Shimizu

Kimura

Funahashi

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

We were the first to report that N 3 -phenacyluridine (1h) (0.5 mmol/mouse) injected by i.c.v. exhibited antinociceptive effect by the tail pinch, hot plate and acetic-acid induced abdominal constriction method. 1) In connection with this finding, uridine is known to possess central nervous system (CNS) depressant effects such as anticonvulsant activity and decreasing spontaneous activities in mice.2,3) CNS depressant effects of uridine were partly explained through the action on the GABA receptor.4) In addition, uridine was reported to have the natural sleep-promoting effect by intracerebral infusion to rats, 5) and the potent sedative-hypnotic activity of N 3 -substituted uridine was also revealed in mice.6) Further studies have been conducted using thymidine, 2Ј-deoxyuridine, 6-azauridine, 2Ј,3Ј-O-isopropylideneuridine as lead compounds. The results indicated that 1h was the most potent hypnotic compound among derivatives tested. [7][8][9][10][11][12][13][14][15][16] Those N 3 -substituted pyrimidine nucleosides also possess certain pharmacological effects i.e., barbiturate-and/or benzodiazepineinduced sleep prolonging effects, motor incoordination, decreasing spontaneous activity, and so on. However, the antinociceptive effects of pyrimidine nucleosides and their derivatives have not been well investigated. Since 1h has the antinociceptive property, we, therefore, synthesized series of the derivatives of N 3 -phenacyl pyrimidine nucleosides in order to find more potent antinociceptive compounds than 1h.The present study evaluated the antinociceptive effects of N 3 -substituted derivatives synthesized from 6 kinds of pyrimidine nucleosides in mice. ChemistryThe structural modification was mainly carried out at the N 3 -position of the pyrimidine ring. Seventy eight of N 3 -substituted pyrimidine nucleosides, methyl (1-6 a), ethyl (1-6 b), allyl (1-6 c), benzyl (1-6 d), xylyl (methylbenzyl) (1-6 e, f, g), phenacyl (1-6 h), methoxyphenacyl (1-6 i, j, k) and dimethoxyphenacyl derivatives (1-6 l, m), were synthesized from uridine (1), thymidine (2), 2Ј-deoxyuridine (3), 6-azauridine (4), 2Ј,3Ј-O-isopropylideneuridine (5), and arabinofuranosyluracil (6) as lead compounds according to the method of reported previously. 6-17) Results and DiscussionThe antinociceptive effects of uridine (1) and its derivatives at the dose of 0.5 mmol/mouse by i.c.v. injection are summarized in Table 1. Uridine (1), the alkyl and allyl compounds 1a-c were inactive or only slightly active by the hot plate test, whereas benzyl and phenacyl substituted uridines (1d, h) possessed 22 and 16% of the activities, respectively. The results supported that 1h possessed the antinociception in mice reported previously.1) The other analogues, N 3 -o-, m-, and p-xylyl-(1e-g), and N -o, m, and p-methoxyphenacyl

show abstract

Elimination reactions on the di- and trimesylated derivatives of N3-benzyluridine

Cited by 32 publications

References 9 publications

Synthesis of 5-(Carboranylalkylmercapto)-2‘-deoxyuridines and 3-(Carboranylalkyl)thymidines and Their Evaluation as Substrates for Human Thymidine Kinases 1 and 2

Synthesis of 5-(Carboranylalkylmercapto)-2‘-deoxyuridines and 3-(Carboranylalkyl)thymidines and Their Evaluation as Substrates for Human Thymidine Kinases 1 and 2

Synthesis of Purine and Pyrimidine 3‘-Amino-3‘-deoxy- and 3‘-Amino-2‘,3‘-dideoxyxylonucleosides

Synthesis of N3-Substituted Uridine and Related Pyrimidine Nucleosides and Their Antinociceptive Effects in Mice

Contact Info

Product

Resources

About