Benzyl Glycidyl Ether Research Articles

Selective cleavage of the linear ether bond in benzyl glycidyl ether and triphenylmethyl glycidyl ether by potassium alkalide as two-electron-transfer reagent

The linear ether bond was exclusively cleaved in benzyl glycidyl ether and triphenylmethyl glycidyl ether under the influence of K −, K +(15-crown-5) 2 ( 1), whereas the strongly strained three-membered oxacyclic ring remained undisturbed. Potassium glycidoxide and benzylpotassium were found as the primary reaction products of benzyl glycidyl ether with 1. Subsequently, benzylpotassium reacted with benzyl glycidyl ether giving the next potassium glycidoxide molecule and bibenzyl. Benzyl phenyl ether was used as a model compound to explain the mechanism of bibenzyl formation. The reaction of triphenylmethyl glycidyl ether with 1 resulted in potassium glycidoxide and stable triphenylmethylpotassium. After treating with a quenching agent a new glycidyl ether or glycidyl ester was obtained from potassium glycidoxide. These results were found when the reaction occurred at the excess of glycidyl ether. In another case, i.e. at the excess of 1 further reactions took place with the participation of potassium anions and various new compounds were observed in the reaction mixture after benzylation or methylation. Thus, the method of substrates delivery influences the course of studied processes in a decisive way.

Discovery and characterization of the potent, selective and orally bioavailable MMP inhibitor ABT-770

Modification of the biphenyl portion of MMP inhibitor 2a gave analogue 2i which is greater than 1000-fold selective against MMP-2 versus MMP-1. The stereospecific synthesis of both enantiomers of 2i was achieved beginning with ( S)- or ( R)-benzyl glycidyl ether. The ( S)-enantiomer, 11 (ABT-770), is orally bioavailable and efficacious in an in vivo model of tumor growth.

ChemInform Abstract: Total Synthesis of (+)-Prelaureatin and (+)-Laurallene.

The first total syntheses of (+)-prelaureatin and (+)-laurallene are described. An asymmetric glycolate aldol addition was followed by a ring-closing metathesis to close the eight-membered ring allowing construction of the oxocene core of (+)-prelaureatin and (+)-laurallene in seven synthetic steps from (R)-benzylglycidyl ether.

Total Synthesis of (+)-Prelaureatin and (+)-Laurallene

The first total syntheses of (+)-prelaureatin and (+)-laurallene are described. An asymmetric glycolate aldol addition was followed by a ring-closing metathesis to close the eight-membered ring allowing construction of the oxocene core of (+)-prelaureatin and (+)-laurallene in seven synthetic steps from (R)-benzylglycidyl ether.

Enantioselectivities of yeast epoxide hydrolases for 1,2-epoxides

Kinetic resolution of homologous series of unbranched 1,2-epoxyalkanes (C-4 to C-12), 1,2-epoxyalkenes (C-4, C-6 and C-8), a 2,2-dialkylsubstituted epoxide (2-methyl-1,2-epoxyheptane) and a benzyloxy-substituted epoxide (benzyl glycidyl ether) was investigated using resting cells of 10 different yeast strains. Biocatalysts with excellent enantioselectivity (E>100) and high initial reaction rates (>300 nmol/min/mg dry weight) were found for the 2-monosubstituted aliphatic epoxides C-6 to C-8. Yeast strains belonging to the genera Rhodotorula, Rhodosporidium and Trichosporon all preferentially hydrolyzed ( R)-1,2-epoxides with retention of configuration. The epoxide hydrolases of all the yeast strains are membrane-associated.

Epoxide hydrolase activity of Chryseomonas luteola for the asymmetric hydrolysis of aliphatic mono-substituted epoxides

Asymmetric hydrolysis of a homologous range of straight chain 1,2-epoxyalkanes was achieved using whole cells of Chryseomonas luteola. Depending on the chain length, hydrolyses of the racemic epoxides afforded optically active epoxides and diols with varying degrees of optical purity. In the case of 1,2-epoxyoctane, the enantiomeric excess of the remaining (S)-epoxide and formed (R)-diol was excellent (ees > 98% and eep = 86%). This is the first report of a bacterial epoxide hydrolase with such unusual enantioselectivity for terminal mono-substituted epoxides bearing no directing group on the chiral C-2 carbon. Benzyl glycidyl ether and the 2,2-disubstituted epoxide, 2-methyl-1,2-epoxyheptane, were hydrolysed, but no enantioselectivity was observed. © Rapid Science Ltd. 1998

Synthesis of Racemic 5-Substituted 1-(2,3-Dihydroxypropyl)-6-azauracils and Their Isosteric Isomers

Abstract Acyclic nucleoside analogues of antiviral DHPA and HPMPA have been prepared. Coupling of silylated 6-azauracils with benzyl glycidyl ether and stannic chloride followed by the deprotection with boron trichloride gave 1-(2,3-dihydroxypropyl)-6-azauracils (3) in good overall yields. Reaction of silylated 6-azauracil and epichlorohydrin with or without catalytic stannic chloride afforded 1-(2-chloro-3-hydroxypropyl)-6-azauracil (4a) and 1-(3-chloro-2-hydroxypropyl)-6-azauracil (6a) respectively. Coupling of silylated 6-azaisocytosine under the same reaction conditions provided 1-(2,3-dihydroxypropyl)-6-azaisocytosine (9) and 1-(2-chloro-3-hydroxypropyl)-6-azaisocytosine (10) respectively. None of the compounds exhibited significant antiviral activity against herpes simplex viruses.

Synthesis of 1‐[(3‐Halo‐1‐Hydroxy‐2‐Propoxy)methyl]uracil and Thymine as Potential Antiviral Agents

Abstract3′‐Halogen acyclonucleoside analogs have been prepared. The starting material, benzyl glycidyl ether (5), prepared from eplchlorohydrin and sodium benzyloxidc, underwent ring opening by soft halogen ions to give l‐benzyloxy‐3‐fluoro‐2‐propanol (6), l‐bcnzyloxy‐3‐chloro‐2‐propanol (7), and l‐benzyloxy‐3‐ bromo‐2‐propanol (8) respectively. The treatment of 5 with lithium iodide in the presence of acetic acid provided 1‐benzyloxy‐3‐iodo‐2‐propanol (9). The treatment of 8 with sodium iodide in anhydrous acetone also produced l‐benzyloxy‐3‐iodo‐2‐propanol (9). Chloromethylation of these halohydrins 6‐9 using paraformaldehyde and hydrogen chloride gas produced the chloromcthyl ethers 10‐13. These chloromethyl ethers without further purification were allowed to react with the silylated bases 16‐17, previously prepared by silylating the bases 14‐15 with HMDS in the presence of ammonium sulfate to give 1‐ [(l‐benzyloxy‐3‐halogen‐2‐propoxy)methyl]uracils and thymines 19‐25. The target compounds 26‐33 were obtained respectively after the debcnzylation of 18‐25. Compounds 26, 27, 30 and 31 had no significant cell toxicity in the range of concentrations 0.001‐20 mM. Compounds 26, 27, 28 and 29 have no significant activity against HSV II (for less than 2 mM there is a cytopathic effect). Compounds 30, 31, 32 and 33 show no activity against HSV II virus even at the level 20 mM.

Synthesis and Absolute Configuration of a Cytotoxic Fatty Acid Isolated from the Mushroom,Hericium erinaceum

The naturally occurring (–)-enantiomer of a fatty acid isolated from the mushroom (Hericium erinaceum) was synthesized from (R)-(–)-benzyl glycidyl ether in 8 steps. A comparison of the specific rotation of the synthetic sample with that of the natural compound established the absolute configuration of the latter.

ChemInform Abstract: A Two‐Step Synthesis of (R)‐ and (S)‐Benzyl Glycidyl Ether.

ChemInform Abstract: A Two‐Step Synthesis of (R)‐ and (S)‐Benzyl Glycidyl Ether.

A two-step synthesis of ( R)- and ( S)-benzylglycidyl ether

Ring opening of ( R)- and ( S)-glycidyl tosylates with benzyl alcohol, followed by treatment with K 2CO 3/MeOH gave ( S)-(+)- and ( R)-(-)-benzylglycidyl ether in 90% overall yield.

Mutagenicities of glycidyl ethers for Salmonella typhimurium: Relationship between mutagenic potencies and chemical reactivity

The lethal and mutagenic effects of ethyl, benzyl, 1-naphthylmethyl, 2-naphthylmethyl, 1-naphthylethyl, 2-naphthylethyl and 9-anthrylmethyl glycidyl ethers on Salmonella typhimurium (TA100, TA1535, TA98 and TA1538) were investigated. LD 30-value became smaller with an increase in compound hydrophobicity. The mutagenicities of these compounds in TA100 increased in the order: 1-naphthylethyl glycidyl ether<2-naphthylethyl glycidyl ether<benzyl glycidyl ether<2-naphthylmethyl glycidyl ether<1-naphthylmethyl glycidyl ether<9-anthrylmethyl glycidyl ether. 1-Naphthylmethyl and 2-naphthylmethyl glycidyl ethers were mutagenic toward TA1535. In TA98, 1-naphthylmethyl and 9-anthrylmethyl glycidyl ethers showed mutagenic activity and 9-anthrylmethyl glycidyl ether was more mutagenic than 1-naphthylmethyl glycidyl ether. 9-Anthrylmethyl glycidyl ether was also active in TA1538. In the reaction of glycidyl ethers with deoxyguanosine and related compounds, glycidyl ethers attacked at only N-7 of guanine. The alkylation rates of glycidyl ethers toward guanine residues in DNA were determined and the exciplex-formation ability of 7-substituted guanines was studied. The reactivity of glycidyl ethers with guanine residues in DNA has not provided a sufficient explanation for the variation in mutagenic potencies of glycidyl ethers.