Jack C. Kim

The operation of H-atom and TMS-group transfer processes in the photochemistry of silylamidoalkyl- and silylalkyl-ketones and -phthalimides

Abstract Photoreactions of silylamidoalkyl- and silylalkyl-ketones and N-silylethylphthalimide operate by competitive H-atom and TMS-group transfer routes and whose relative efficiencies are influenced by side-chain and carbonyl substituents, and solvent.

A novel azomethine ylid forming photoreaction of N-trimethylsilylmethylphthalimides

Abstract Irradiation of N-trimethylsilylmethylphthalimide and its 1,8-naphthalimide analog leads to generation of azomethine ylids by C to O TMS -transfer processes.

Preparation of N′-substituted anilino-N-methyl-N′nitrosoureas as candidate antitumor agents

Various N′-substituted anilino-N-methyl-N′-nitrosoureas(2a-n) were easily prepared from the reaction of substituted phenylhydrazines (3-, 4-CH3, 3-, 4-OCH3, 3-, 4-F, 3-, 4-Cl, 4-Br, 2-, 3-, 4-NO2, 2, 4-(NO2)2 with methyl isocyanate, followed by the nitrosation with 99% HCOOH and dry sodium nitrite powder. Surprisingly, of these series of analogus, the anilino-nitrosoureas substituted with eletron-withdrawing nitro groups (2k-n) showed significantly low ED50 values of 1.4≈3.4μg/ml. In addtion, none of these compounds subtituted with electron-donating groups exhibited cytotoxicities.

Synthesis and evaluation of antitumor activity of a homologous series of 1-(ω-cyanoalkyl)-and 1,3-bis (ω-cyanoalkyl)uracil nucleoside analogues

Acyclonucleoside homologues of 1-(ω-cyanoalkyl)-and 1,3-bis (ω-cyanoalkyl) uracils were synthesized by the series of alkylation reactions of uracil with the ω-chloroalkyl nitrile (Cl-(CH2)n-CN; n=1, 2, 3, 4) in DMSO under 50∼75°C temperature. The 1-(ω-cyanoalkyl)-and 1,3-bis(ω-cyanoalkyl) uracils were separated either by the fractional crystallization or column chromatography. The antitumor activities for these synthesized compounds were determined against four cell lines (J-82 cell, P388 cell, FM-3A cell and U-937 cell lines). These compounds failed to exhibit any significant antitumor activity.

Synthesis and primary screening for growth inhibitors of L1210 cells of cholesterylp-[3-(2-chloroethyl)-3-nitrosoureido] phenylthioacetate

Cholesterylp-[3-(2-chloroethyl)-3-nitrosoureido] phenylthioacetate (2) was synthesizedian intermediate,p-[3-(2-chloroethyl)-3-nitrosoureido] phenylthioacetic acid (1) is a congener of an antitumor chlorambucil which both the-CH2CH2-linkage and-N(CH2CH2Cl)2 group of chlorambucil molecule is doubly modified into the respective-S-linkage and-NH−CO−NNO−CH2CH2Cl group. The attackment of cholesterol moiety as a carrier group top-[3-(2-chloroethyl)-3-nitrosoureido] phenylthioacetic acid was accomplished through the esterification of cholesterol withp-[3-(2-chloroethyl)-3-nitrosoureido] phenylthioacetyl chloride which was obtained from the treatment ofp-[3-(2-chloroethyl)-3-nitrosoureido] phenylthioaceticacid with SOCl2.p-[3-(2-chloroethyl)ureido]-phenylthioacetic acid was nitrosated with NaNO2 in 98≈100% HCOOH to give exclusivelyp-[3-(2-chloroethyl)-3-nitrosoureido]phenylthioacetic acid. Antitumor evaluation of compounds, 1 and 2 on L 1210 leukemia did show significant activity (ED40:I. 14μg/ml and 8.4μg/ml. respectively). Further studies were subjected.

A high yield conversion of n-norapomorphine from apomorphine

A rapid, high yield of N-norapomorphine from apomorphine was accomplished by allowing it to react with phenyl chloroformate without isolating and purifying the intermediate carbamate, and have found that the crude carbamate can be easily cleaved in situ with a 1∶1 mixture of 64% and 95% hydrazine to afford analytically pure N-norapomorphine, in 81% overall yields. Previously, various other methods gave an untoward ring opening reactitions and scission of the hydropyridine ring in the apomorphine series.

Synthesis and antitumor evaluation of acyclic 1-[ω-(N′-2-chloroethyl-N′-nitrosoureido)alkyl]thymidine nucleoside analogues

In the preparation of acyclic thymidine nucleoside analogues, K2CO3 (or NaH) treated thymine in DMSO was alkylated with ω-chloroalkyl nitrite (Cl-(CH2)n-CN; n=1, 2, 3, 4) to provide an isomeric mixture of 1-(ω-cyanoalkyl)thymine (2a-d) and 1,3-bis(ω-cyanoalkyl)thymine in approximately 5∶1 ratios. Reduction of the cyano function2a-d with NaBH4/CoCl2·6H2O gave the corresponding 1-(ω-aminoalkyl)thymine (3a-d). The newly formed primary amino function in3a-d was directly reacted with 2-chloroethylisocyanate to afford the 1-[ω-(N′2-chloroethy-lureido) alkyl]thymine (4a-d) in good yields. Nitrosation of 1-[5-(N′-2-chloroethylureido)pentyl] thymine (4d) with glacial acetic acid and dry NaNO2 powder in anhydrous CH2Cl2 gave two types of regioisomeric nitrosoureas, 1-[5-(N′-2-chloroethyl-N′-nitrosoureido)pentyl]thymine (5d) and 1-[5-(N′-2-chloroethyl-N-nitrosoureido)pentyl]thymine in approximately 5∶1 ratios. The in vitro cytotoxicity of the synthesized compounds (2a-d, 3a-d, 4a-d and5a-d) against three cell lines (K-562, P-388 and FM-3A) are measured as IC50 values. Compounds3d and4c showed moderate activities against all three cell lines, and all other compounds were found to be not active.

Transformation of 5,6-dimethoxy-2-amino-1-tetralol hydrochloride into 5,6-dimethoxy-2-tetralone

The reduction procedure of 5,6-dimethoxy-2-amino-1-tetralone with sodium bis-(2-methoxy)-aluminum hydride, followed by palladium on charcoal in the presence of HClO4 gave a major reduction product of 5,6-dimethoxy-2-amino-tetralin, along with a small amount of a transformed 5,6-dimethoxy-2-tetralone. The isolated intermediate, 5,6-dimethoxy-2-amino-1-tetralol hydrochloride yielded exclusively 5,6-dimethoxy-2-tetralone under catalytic acidic conditions (acid treatment). The unusual rearangement was verified on the basis of IR, NMR and the result of elemental analysis. A plausible mechanism for the rearrangement is discussed.