6943-87-9Relevant academic research and scientific papers
Sulfonyl-containing aldophosphamide analogues as novel anticancer prodrugs targeted against cyclophosphamide-resistant tumor cell lines
Jain, Monish,Fan, Junying,Baturay, Nesrine Z.,Kwon, Chul-Hoon
, p. 3843 - 3852 (2007/10/03)
A series of sulfonyl-group containing analogues of aldophosphamide (Aldo) were synthesized as potential anticancer prodrugs that liberate the cytotoxic phosphoramide mustards (PM, IPM, and tetrakis-PM) via β-elimination, a nonenzymatic activation mechanism. Kinetic studies demonstrated that all these compounds spontaneously liberate phosphoramide mustards with half-lives in the range of 0.08-15.2 h under model physiological conditions in 0.08 M phosphate buffer at pH 7.4 and 37 °C. Analogous to Aldo, the rates of β-elimination in all compounds was enhanced in reconstituted human plasma under same conditions. The compounds were more potent than the corresponding phosphoramide mustards against V-79 Chinese hamster lung fibroblasts in vitro (IC50 = 1.8-69.1 μM). Several compounds showed excellent in vivo antitumor activity in CD2F1 mice against both P388/0 (Wild) and P388/CPA (CP-resistant) tumor cell lines.
Reactivity of N-phenyl silylated ketenimines with electrophilic reagents
Fromont, Christophe,Masson, Serge
, p. 5405 - 5418 (2007/10/03)
We report the reactivity of new Cβ silylated ketenimines (4, 5, 6) and lithiated-silylated ketenimine 3 [easily generated from lithiated S-methyl- N-phenyl-trimethylsilylethanimidothioate 2] toward electrophilic reagents. Reactions of these ketenimines with strong electrophilic reagents such as sulfanyl chloride (PhSCl) gave access to new sulfanylated ketenimines. With less reactive species [benzenesulfinyl chloride (PhS(O)Cl), p-toluenesulfonyl chloride, trimethylhalosilanes, diisopropyl chlorophosphate, acetyl chloride and propylene oxide] and 3, the addition took place either on Cβ or on the nitrogen atom leading to relatively unstable functionalised ketenimines or new silylated ynamines respectively.
2-iminobenzothiazoline derivatives, their preparation and pharmaceutical compositions containing them
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, (2008/06/13)
Compounds of the formula: STR1 in which - R1 denotes a polyfluoroalkoxy or polyfluoroalkyl radical, and - R2 denotes either a chain --CH2 --(CH(R4))n --R3, in which R3 denotes a dialkylamino, piperidino, 1-pyrrolidinyl, mercapto, acylthio, alkylthio, alkylsulphinyl or alkylsulphonyl radical, R4 denotes a hydrogen atom or an alkyl radical and n is equal to 0 or 1, or a residue of formula: STR2 the said alkyl and alkoxy radicals and portions containing 1 to 4 carbon atoms each in a straight or branched chain and said the acyl portions containing 2 to 4 carbon atoms each, and the salts of these compounds, are useful in the treatment of diseases in which glutamate is implicated.
Simplified Method of Ascertaining Steric Effects in Electrophilic Addition Reactions. A Comparison of Bromination, Oxymercuration, and Hydroboration
Nelson, Donna J.,Cooper, Penny J.,Soundararajan, Raman
, p. 1414 - 1418 (2007/10/02)
Correlations of ionization potentials (IP's) versus relative reactivities of a variety of alkenes toward bromination, oxymercuration, and hydroboration show very good (r=0.83) to excellent (r=0.98) agreement.The use of alkenes having a broad range of steric requirements and electronic effects reveals that bromination is independent of steric effects while oxymercuration and hydroboration each exhibit a natural separation into sterically similar groups, within which alkene IP's correlate with relative reactivities.In hydroboration of allylic compounds, characteristicsof the HOMO influence the regioselectivity as well as the relative reactivity.The data indicate that the transition states of the rate-determining steps of oxymercuration and hydroboration are similar, but both are different from that of bromination.
β-Substituted Organolithium Compounds from Chlorohydrins: Application to the Direct Synthesis of Bifunctionalized Organic Cpmpounds
Barluenga, Jose,Florez, Josefa,Yus, Miguel
, p. 3019 - 3026 (2007/10/02)
The reaction of different chlorohydrins with n-butyl-lithium at -78 deg C followed by metallation wiht lithium naphthalenide at the same temperature leads to very reactive organolithium compounds bearing an alkoxide function at the β-position with respect to metal.The reaction of these intermediates with several electriphiles leads to mono- as well as bi-functionalized organic compounds.Thus, treatment of these dianions with deuterium oxide, oxygen, carbon dioxide, benzyl bromide, dimethyl disulphide, and carbonyl compounds, gave 2-deuterioalcohols, 1,2-diols, β-hydroxy-acids, 2-benzyl alcohols, 2-hydroxy-thioethers, and 1,3-diols respectively.The preparation of β-substituted organolithium derivatives can be alternatively carried out starting from α-chloroketones by the same procedure.When the lithium atom is linked to a secondary carbon atom the dianions are very unstable and decompose, even at -100 deg C, by β-elimination yielding the corresponding olefins.
Regiochemistry and reactivity in the chlorination of sulfides
Hancock, James Reid,Hardstaff, William Rayne,Johns, Paul Alan,Langler, Richard Francis,Mantle, William Stanley
, p. 1472 - 1480 (2007/10/02)
Huheey's original method for the calculation of substituent electronegativities is modified so that isomeric groups have different electronegativities.The modified form of Huheey's method is then employed to show that our previously published method for anticipating regiochemistry in asymmetric sulfide chlorination, i.e., ΔXP calculations for the α and α' substituents in the sulfide substrates, is successful in all fifty known cases.A new reactivity function (RP) is defined, for the sulfenium ion intermediates, which permits one to anticipate when substrates become inert to chlorine in exhaustive chlorinations conducted in aprotic media.
β-Substituted Organolithium Compounds; Direct Preparation and Reactivity
Barluenga, Jose,Florez, Josefa,Yus, Miguel
, p. 1153 - 1154 (2007/10/02)
Very reactive organolithium compounds bearing an alkoxide function at the β-position with respect to the metal are obtained by direct metallation with lithium naphthalenide at low temperature of the corresponding lithium chlorohydrin salt; the reaction of these dianions with different electrophilic agents leads to the corresponding mono- and bi-functionalized compounds.
β-Substituted Organolithium Compounds. Reaction with Alkyl Halides, Dimethyl Disulfide, and Imines
Barluenga, Jose,Fananas, Francisco J.,Villamana, Jorge,Yus, Miguel
, p. 1560 - 1564 (2007/10/02)
The reaction of β-substituted organolithium derivatives with several electrophiles leads to mono- as well as bifunctionalized organic compounds.Thus, by treatment of these dianions with alkyl halides a direct attack on the carbanionic carbon atom is performed, giving as a result substituted amines.When dimethyl disulfide is used, β-amino and β-hydroxy thioethers are obtained.Finally, on reaction with imines, 1-amino-3-hydroxy compounds and 1,3-diamines are obtained.Since these dianions are easily preparated by mercury-lithium transmetalation from β-substituted organomercurials resulting from the addition of mercury(II) salts to olefins, this whole process gives an appropriate way of functionalizing olefins.
Solvomercuration-Demercuration. 9. Oxymercuration-Demercuration of Chloro-, Epoxy-, and Thiomethyl-Substituted Alkenes
Brown, Herbert C.,Lynch, Gary J.
, p. 930 - 939 (2007/10/02)
The oxymercuration-demercuration (OM-DM) of allyl, crotyl, 3-buten-1-yl, 4-penten-1-yl, and 5-hexen-1-yl chlorides and methyl sulfides as well as 3,4-epoxy-1-butene, 4,5-epoxy-1-pentene, and 5,6-epoxy-1-hexene has been studied.Allyl chloride undergoes a slow but normal OM to give the Markovnikov oxymarcurial.However, in situ demercuration under the standard conditions (NaOH, NaBH4) gives only allyl alcohol.Fortunately, demercuration with an ethanolic solution of sodium borohydride results in high yields of the chlorohydrin accompanied by small amounts of propylene oxide.In contrast, crotyl chloride fails to give any products resulting from the OM-DM sequence.Thus, 3-buten-2-yl chloride underwent only solvolytic reaction while 2-methylallyl chloride underwent exclusive OM to give, upon DM, the expected Markovnikov chlorohydrin.Similarly, 3-buten-1-yl chloride underwent exclusive hydration under the standard OM-DM conditions.In the case of 4-penten-1-yl chloride, the C1-C5 neighboring-group participation was seen during OM.However, 5-hexen-1-yl chloride showed exclusive hydration to give a 94percent yield of the Markovnikov chlorohydrin.The approximate rates of solvolysis of a series of representative alkyl halides have been determined under the OM conditions.The OM-DM of 3,4-epoxy-1-butene proceeded to give hydrated products although the yield was low, ca. 60percent.On the other hand, 4,5-epoxy-2-pentene gave products arising only from participation of the epoxide ring in the OM stage.Moreover, the yields of these products are very low, only ca. 15percent.By contrast, the OM-DM of 4,5-epoxy-1-pentene proceeds cleanly, giving a 96percent yield of the Markovnikov epoxy alcohol.In the case of 5,6-epoxy-1-hexene, ca. 80percent of the products arise from epoxide participation in the OM stage.With the exception of the crotyl derivative, the (methylthio)alkenes undergo hydration cleanly, although slowly, to give approximately 70-80percent yields of the thio alcohols.The crotyl alkene gave 3-butene-2-ol in only ca. 20percent yield.
