[(η5‐C5R5)TiCl2(η5‐C5H4SiMe2)]2O·nCH2Cl2

The first title metallocene, 1,3‐bis(dichlorotitanocene)‐1,1,3,3‐tetramethyldisiloxane dichloromethane solvate, [(η⁵‐C₅H₅)­TiCl₂­(η⁵‐C₅H₄­Si­Me₂)]₂O·­CH₂Cl₂, (I), crystallizes in space group P2₁/c. Compound (I) represents the first crystal structure of a bimetallic siloxy‐bridged titanocene. The geometric parameters of (I) are similar to those of the parent titanocene; however, the disiloxane substituents adopt an unexpected eclipsed conformation. The second title metallocene, 1,3‐bis­[(penta­methyl­cyclo­penta­dienyl)­(cyclo­penta­dien­yl)­titanium dichloride]‐1,1,3,3‐tetra­methyl­disiloxane, [(η⁵‐C₅‐Me₅)­TiCl₂­(η⁵‐C₅H₄­Si­Me₂)]₂O, (II), represents the second crystal structure of a bimetallic siloxy‐bridged titanocene and crystallizes in the space group P2₁/n. Compound (I) possesses non‐crystallographic twofold molecular symmetry and both metal centers adopt pseudo‐tetrahedral geometries. The geometric parameters of (II) are similar to those of the mixed titanocene Cp*CpTiCl₂ (Cp* = C₅Me₅) and the disiloxane substituents adopt a staggered conformation.     

Synthesis of 2′-Deoxyisoguanosine 5′-Triphosphate and 2′-Deoxy-5-methylisocytidine 5′-Triphosphate

The syntheses of the 5′-triphosphates of 2′-deoxyisoguanosine (=p₃isoG_d) and 2′-deoxy-5-methylisocytidine (=p₃me⁵isoC_d), two new bases for the genetic alphabet, are described. The triphosphates were synthesized from the corresponding nucleosides using a transient-protection procedure. The introduction of a methyl group at the 5-position of 2′-deoxyisocytidine remarkably improved the stability of the triphosphate. Characterization of the triphosphates included enzymatic incorporation opposite the complementary base in a template oligonucleotide.     

Regio‐ and Chemoselective Metalation of Chloropyrimidine Derivatives with TMPMgCl⋅LiCl and TMP2Zn⋅2 MgCl2⋅2 LiCl

Efficient zincation and magnesiation of chlorinated pyrimidines can be performed at convenient temperatures (e.g., 25 and 55 °C) by using TMPMgCl?LiCl and TMP₂Zn?2 M gCl₂?2 LiCl (TMP=2,2,6,6‐tetramethylpiperidyl) as effective bases. Quenching of the resulting zincated or magnesiated pyrimidines with various electrophiles furnishes highly functionalized pyrimidines in 51–93 % yield. Oxidative aminations were carried out, thus leading to aminated pyrimidines. By using this methodology, we have also prepared pharmaceutically relevant pyrazolopyrimidines and the fungicide Mepanipyrim.     

[Co(g5‐Me5C5)(g3‐tBu2PPCH–CH3)] aus [Co(g5‐Me5C5)(g2‐C2H4)2] und tBu2P–P=P(Me)tBu2

Coordination Chemistry of P‐rich Phosphanes and Silylphosphanes. XVII [1] [Co(g⁵‐Me₅C₅)(g³‐^tBu₂PPCH–CH₃)] from [Co(g⁵‐Me₅C₅)(g²‐C₂H₄)₂] and ^tBu₂P–P=P(Me)^tBu₂ [Co(η⁵‐Me₅C₅)(η³‐^tBu₂PPCH–CH₃)] 1 is formed in the reaction of [Co(η⁵‐Me₅C₅)(η²‐C₂H₄)₂] 2 with ^tBu₂P–P 4 (generated from ^tBu₂P–P=P(Me)^tBu₂ 3 ) by elimination of one C₂H₄ ligand and coupling of the phosphinophosphinidene with the second one. The structure of 1 is proven by ³¹P, ¹³C, ¹H NMR spectra and the X‐ray structure analysis. Within the ligand ^tBu₂P¹P²C¹H–CH₃ in 1 , the angle P1–P2–C1 amounts to 90°. The Co, P1, P2, C1 atoms in 1 look like a „butterfly”︁. The reaction of 2 with a mixture of ^tBu₂P–P=P(Me)^tBu₂ 3 and ^tBu–C?P 5 yields [Co(η⁵‐Me₅C₅){η⁴‐(^tBuCP)₂}] 6 and 1 . While 6 is spontaneously formed, 1 appears only after complete consumption of 5 .     

5a-Carba-β-D-, 5a-Carba-β-L- and 5-Thio-β-L-xylopyranosides as New Orally Active Venous Antithrombotic Agents

Mitsunobu displacement of (−)-(1S,4R,5S,6S)-4,5,6-tris{[(tert-butyl)dimethylsilyl]oxy}cyclohex-2-en-1-ol ((−)- 12 ; a (−)-conduritol-F derivative) with 4-ethyl-7-hydroxy-2H-1-benzopyran-2-one ( 16 ) provided a 5a-carba-β-D -pyranoside (+)- 17 that was converted into (+)-4-ethyl-7-[(1′R,4′R,5′S,6′R)-4′,5′,6′-trihydroxycyclohex-2′-en-1′-yloxy]-2H-1-benzopyran-2-one ((+)- 5 ) and (+)-4-ethyl-7-[(1′R,2′R,3′S,4′R)-2′,3′,4′-trihydroxycyclohexyloxy]-2H-1-benzopyran-2-one ((+)- 6 ). The 5a-carba-β-D -xyloside (+)- 6 was an orally active antithrombotic agent in the rat (venous Wessler's test), but less active than racemic carba-β-xylosides (±)- 5 and (±)- 6 . The 5a-carba-β-L -xyloside (−)- 6 was derived from the enantiomer (+)- 12 and found to be at least 4 times as active as (+)- 6 . (+)-4-Cyanophenyl 5-thio-β-L -xylopyranoside ((+)- 3 ) was synthesized from L -xylose and found to maintain ca. 50% of the antithrombotic activity of its D -enantiomer. Compounds (±)- 5 , (±)- 6 , and (−)- 6 are in vitro substrates for galactosyltransferase 1.     

Syntheses of 5′-amino-2′,5′-dideoxy-2′,2′-difluorocytidine derivatives as novel anticancer nucleoside analogs

A novel class of 5′-amino-2′,5′-dideoxy-2′,2′-difluorocytidine derivatives has been synthesized in order to identify anticancer nucleoside analogs. Several synthetic routes were devised and implemented which relied upon either S_N2 displacement or reductive amination to provide the desired derivatives.     

5‐Methyl‐2‐thiouracil

The molecular structure of the title compound, also known as 2‐thio­thymine [systematic name: 2,3‐di­hydro‐5‐methyl‐2‐thioxopyrimidin‐4(1H)‐one], C₅H₆N₂OS, is similar to that of thymine, with only small changes in the ring structure, apart from a significant difference at the substitution site [S=C = 1.674 (1) Å]. The mol­ecules are connected by hydrogen bonds, with N—H?O = 2.755 (2) Å and N—H?S = 3.352 (1) Å. The hydrogen‐bond network is different from that in thymine, since it involves all the donor and acceptor atoms.     

Concise synthesis of 5-methyl-, 5-formyl,and 5-carboxy analogues of 2′-deoxycytidine-5′-triphosphate

We describe a concise and efficient synthesis of 5-methyl-, 5-formyl-, and 5-carboxy-analogues of 2′-deoxycytidine-5′-triphosphate which are well known for their various biological applications. A protection-free one-pot synthesis was used to convert 5-methyl-2′-deoxycytidine into 5-methyl-2′-deoxycytidine-5′-triphosphate in high yield. 5-Formyl-2′-deoxycytidine-5′-triphosphate was obtained upon photosensitized oxidation (UV-A irradiation, λ ∼365 nm) of an aerated aqueous solution of 5-methyl-2′-deoxycytidine-5′-triphosphate with the use of menadione as the photosensitizer. 5-Formyl-2′-deoxycytidine-5′-triphosphate was converted into 5-carboxy-2′-deoxycytidine-5′-triphosphate by using biphasic TEMPO/BAIB oxidation method in high yield.     

Synthesis of 2′-amino-2′-deoxy-5-fluorocytidine

Acetylation of 2′-deoxy-5-fluoro-2′-trifluoroacetamidouridine with acetic anhydride in pyridine, followed by treatment with phosphorus pentasulfide in refluxing dioxane afforded 3′,5′-di-O-acetyl-2′-deoxy-5-fluoro-2′-trifluorothioacetamido-4-thiouridine ( 3 ). Treatment of 3 with methanolic sodium methoxide furnished 2′-deoxy-2′-trifluorothioacetamido-4-thiouridine ( 4 ), whereas its treatment with methanolic ammonia gave 2′-amino-2′-deoxy-5-fluorocytidine ( 5 ). An alternative approach for the preparation of this compound proceeding from 2′-trifluoroacetamidocytidine was unsuccessful, since the use of acetic anhydride in pyridine led to the replacement of the trifluoroacetyl function by an acetyl group, yielding an intermediate unsuitable for obtaining the target compound. The title compound was inactive at 1 × 10^?4 M concentration against HeLa and leukemia L1210 cells in vitro, but inhibited the in vitro growth of E. coli cells at a concentration of 1 × 10^?7 M. It was also found to be a substrate for CR/dCR deaminase partially purified from human liver, with a Km of 128 μM.     

Syntheses and Anti—inflammatory Actiobn of （η—C5H5）2Ti （Cin）2 and （η—C5H5）2Ti（Tzea）2

Two new Complexes(Cp)2Ti(Cin)2and (CP2)Ti(Tzea)2(CP=Cyclopentadienyl η^5-C5H5)have been synthesized in THF by the reaction of HCin(Cincofen,2-phenylquinoline-4-carboxylic acid)or HTzea(5-phenyltetrazolyl-2-ethanoic acid)with(Cp)2TiCl2,and characterized by elemental analyses,IR,1H NMR and 13C NMR,UV spectra,molar conductivity,TGDTA.In the complexes the carboxyl groups are coordinated to Ti(IV)in a monodentate manner,The inhibitory actions of the complexes on mice ear tumefaction caused by croton oil and the rat foot granulation growth produced by cotton wool are higher than those of the corresponding ligands HCin,HTzea and [(Cp)2TiCl2],while their toxicities are lower than those of the free ligands.ηη