Benzyl formate is found in coffee and coffee products
Peptides containing C-terminal esters are an important class of bioactive molecules that includes a-factor, a farnesylated dodecapeptide, involved in the mating of Saccharomyces cerevisiae. Here, results that expand the scope of solid-phase peptide synthetic methodology that uses trityl side-chain anchoring for the preparation of peptides with C-terminal cysteine alkyl esters are described. In this method, Fmoc-protected C-terminal cysteine esters are anchored to trityl chloride resin and extended by standard solid-phase procedures followed by acidolytic cleavage and HPLC purification. Analysis using a Gly-Phe-Cys-OMe model tripeptide revealed minimal epimerization of the C-terminal cysteine residue under basic conditions used for Fmoc deprotection. 1H NMR analysis of the unfarnesylated a-factor precursor peptide confirmed the absence of epimerization. The side-chain anchoring method was used to produce wild-type a-factor that contains a C-terminal methyl ester along with ethyl-, isopropyl-, and benzyl-ester analogs in good yield. Activity assays using a yeast-mating assay demonstrate that while the ethyl and isopropyl esters manifest near-wild-type activity, the benzyl ester-containing analog is ca. 100-fold less active. This simple method opens the door to the synthesis of a variety of C-terminal ester-modified peptides that should be useful in studies of protein prenylation and other structurally related biological processes.
Benzyl formate occurs in essential oils
T1 - Synthesis and structure-activity studies of benzyl ester meperidine and normeperidine derivatives as selective serotonin transporter ligands
We examined the hydrolysis of dibenzyl ether, benzyl -butyl ether, methyl -butyl ether, methylbenzoate, and diphenylcarbonate in high-temperature liquid water, both with and without added acid or base. The apparent reaction order for H+ did not exceed 0.2 for any of the compounds investigated. This result indicates that hydrolysis of these compounds in high-temperature water (HTW) does not follow the kinetics expected for specific acid catalysis (H+ reaction order = 1.0), as does the hydrolysis at ambient temperatures. Rather, the greater thermal energy in the HTW system allows protonation by water molecules to become faster than protonation by H+ at near-neutral conditions. Because the water-catalyzed path is faster, the occurrence of these acid-catalyzed reactions in HTW with no added acid is not due to the elevated value of w, the ion product. This finding contradicts the conventional wisdom in this field.
Recommendation for benzyl bromoacetate flavor ..
Our efforts to develop novel molecular scaffolds targeting monoamine transporter systems have led to the development of several classes of selective DAT ligands and selective SERT ligands.- Previously, we have reported on a series of derivatives of meperidine (1) that exhibited modest potency and selectivity for the SERT ()., However, unlike the prototypical SSRIs fluoxetine and paroxetine, the meperidine analogues 2 lack a secondary amine and two aromatic moieties common to the SERT pharmacophore., In light of these deficiencies it was of interest to examine this class of meperidine-based SERT ligands to determine if SERT potency could be improved and the monoamine transporter selectivity influenced by the addition of a second strategically placed aryl ring system. To this end, we envisaged a series of benzyl ester normeperidine derivatives 3 that would be similar to the SERT pharmacophore. As illustrated in , the alignment of predicted favorable solvated conformers of benzyl normeperidine 3, fluoxetine and paroxetine suggested that appropriately substituted normeperidine benzyl esters should exhibit high affinity for the SERT. A normeperidine benzyl ester 3 that exhibited potent SERT affinity could then be evaluated at other monoamine transporters or serotonin receptors to determine the potential focus for medication development (e.g. SSRI, TUI, duel SSRI/5-HT1A antagonists). Herein we report the synthesis and monoamine transporter affinity of novel benzyl ester meperidine and normeperidine derivatives.
Synthesis of carnitine benzyl esters as prodrugs | …
Based upon previous structure-activity studies of meperidine analogues, we focused on four 4-aryl (Ar1) piperidine scaffolds (Ar1 = 3,4-dichlorophenyl, 4-Ph-Ph, 4-I-Ph, 2-naphthyl). Previous studies had shown these aryl groups to contribute to the high potency and selectivity at SERT observed for the meperidine ethyl ester derivatives 2a-d () as well as a variety of piperidine and tropane derivatives.- As illustrated in , an initial series of normeperidine derivatives 4 were prepared from the corresponding ethyl esters 2 using 1-chloroethyl chloroformate (ACE-Cl). This two-step one-pot processs typically afforded the normeperidine derivatives 4 in 59% - 73% yield. The benzyl ester derivatives were prepared from the corresponding nitriles 5 () that were readily available using synthetic methods previously reported from our laboratory. Hydrolysis of the nitrile moiety of 5 was achieved in a methanolic solution of sodium hydroxide (25% wt) at reflux, followed by an acidic work-up (2N HCl) to afford the carboxylic acids 6 as the hydrochloride salts in >90% yield. Without purification, the carboxylic acids 6 were converted into the acid chlorides 7 with thionyl chloride and then treated with the appropriately substituted benzyl alcohol under phase-transfer conditions. This furnished the benzyl esters 8-11 in 25-62% yield for the two-step process. The normeperidine analogues 12-15 were then prepared in 70-85% yield using ACE-CI procedure described above.