• Archives of Pharmacal Research
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• 제21권4호
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• pp.465-469
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• 1998

The search for platinum (II)-based compounds with improved therapeutic properties was prompted to design and synthesize a new family of water-soluble, third generation cis-diaminedichloroplatinum (II) complexes linked to uracil and uridine. Six heretofore unreported uracil and uridine-platinum (II) complexes are; [N-(uracil-5-yl-methyl)ethane-1,2-di-amine]dichloroplatinum (II) (3a), [N-(uracil-6-yl-methyl)ethane-1,2-diaminel dichloroplatinum (II) (3b), t[N-($2^1$, $3^1$,$5^1$-tri-O-acetyl)uridine-5-yl-methyl] ethane-1,2-diamineldichloroplatinum (II) (6a), {[N-($2^1$,$3^1$, $5^1$-tri-O-acetyl) uridine-6-yl-methyl]ethane-1,2-diamine)dichloroplatinum (II) (6b),[N-(uridine- 5-yl-methyl)ethane-1,2-diamine]dichloroplatinum (II) (7a), [N-(uridine-6-yl- methyl)ethane-1,2-diamine]dichloroplatinum (II) (7b). These analogues were prepared from the key starting materials, 5-chloromethyluracil (1a) and 6-chloromethyluracil (1b) which were reacted with ethylenediamine to afford the respective 5-[(2-aminoethyl)aminol methyluracil (2a) and 6-[(2-aminoethyl)amino]methyluracil (2b). The cis-platin complexes 3a and 3b were obtained through the reaction of the respective 2a and 2b with potassium tetrachloroplatinate (II). The heterocyclic nucleic acid bases 1a and 1b were efficiently introduced on the .betha.-D-ribose ring via a Vorbruggen-type nucleoside coupling procedure with hexamethyldisilazane, trimethylchlorosilane and stannic chloride under anhydrous acetonitrile to yield the stereospecific .betha.-anomeric 5-chloromethyl- $2^1$,$3^1$,$5^1$-tri-O-acetyluridine (4a) and 6-chloromethyl-$2^1$,$3^1$,$5^1$-tri-O-acetyluridine (4b), respectively. The nucleosides 4a and 4b were coupled with ethylenediamine to provide the respective 5-[(amino-ethyl)aminolmethyl-$2^1$,$3^1$,$5^1$-tri-O-acetyluridine (5a) and 6-[(aminoethyl)amino] methyl-$2^1$,$3^1$,$5^1$-tri-O-acetyluridine (5b). The diamino-uridines 5a and 5b were reacted with potassium tetrachloroplatinate (II) to give the novel nucleoside complexes, 6a and 6b, respectively which were deacetylated into the free nucleosides, 7a and 7b by the treatment with CH$_{3}$ONa. The cytotoxic activities were evaluated against three cell lines (FM-3A, P-388 and J-82) and none of the synthesized compounds showed any significant activity.

• 대한화학회지
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• 제39권9호
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• pp.715-721
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• 1995

Trans-$[Co(py)_4/Ci_2]^+(py=pyridine)$과 L-proline 및 diimine(=2,2'-bipyridine,1,10-phenanthroline)과의 반응에서 $[Co(L-pro)_2/(bipy)]^+$(L-pro=bipy=2,2'-bipyridine)과 $[Co(L-pro)_2(phen)]^+$(phen=1,10-phenathroline)이 각각 생성되었다. 관 크로마토그래피상에서 입체특이성을 가지는 L-prolinato의 입체선택성으로 인하여 $[Co(L-pro)_2(bipy)]^+$에서는 $Lambda$-trans(N)만이 얻어졌고 $[Co(L-pro)_2(bipy)]^+$에서는 ${\Delta}$-trans(N)과 $Lambda$-cis(O)cis(N)이 얻어졌다. 결정구조 연구의 결과는 다음과 같다: $Lambda$-trans(N)-$[Co(L-pro)_2(bipy)]CIO_4{\cdot}2H_2O$ (1): monoclinic, space group $P2_1(#4)$, a = 9.807(3), b = 10.421(1), c = 12.778(2)${\AA}$, ${\beta}=109.90(2)^{\circ}$, V = 1227.8(5)${\AA}^3$, Z = 2; 1571 data(I>3.0${\sigma}$(I)) R = 0.060 and $R_W = 0.067$; ${\Delta}$-trans(N)-$[Co(L-pro)_2(phen)]Cl{\cdot}_3H_2O$ (2): monoclinic, space group $P2_1(#4)$, a = 9.838(2), b = 12.892(2), c = 10.747(2)${\AA}$, ${\beta}=113.79(2)^{\circ}$, V = 1247.2(4)${\AA}^3$, Z = 2; 2433 data(I>3.0${\sigma}$(I)) R = 0.043 and $R_W = 0.050$.