Esterification of N-protected .alpha.-amino acids with alcohol/carbodiimide/4-(dimethylamino)pyridine. Racemization of aspartic and glutamic acid derivatives

Dhaon, Madhup K.; Olsen, Richard K.; Ramasamy, K.

doi:10.1021/jo00349a028

Cited by 202 publications

(78 citation statements)

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“…ii 97% CL anomer) and Tri uoroethanol, N,N'-Ald!rich.. "A;1 th h die clohe lcarbodiimide (DCCI), 4-(dimethylamino)pyridine (DMAP) were from o er c emicals and solvents in this work were of the highest purity commercially available. Lipases from Candida cylindracea (CCL) and porcine pancreas (PPL) were 'obtained from Sigma Chemical Co. Lipozyme (Dhaon et al, 1982 The reaction and the cation were monitored with thin layer chromate v ra hy pe rf) sihca gel coated glass sheets (Darmstadt, Germany .…”

Section: Methodsmentioning

confidence: 99%

Enzymatic transesterification of monosaccharides and amino acid esters in organic solvents

Park

Yang

1996

Biotechnol Lett

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Lipases and proteases from different sources were screened for their ability to catalyze the transesterification of glucose and activated N-blocked phen fs lalanine. A commercial 8 rotease from Bacillus licheniformis was found to be most e ective for this purpose.n a basis of "C-NMR analysis, .glucose was acylated at the C-6 position. The enzyme showed a broad substrate specificity toward various monosaccharides.

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Section: Methodsmentioning

confidence: 99%

Enzymatic transesterification of monosaccharides and amino acid esters in organic solvents

Park

Yang

1996

Biotechnol Lett

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“…The desired α-cyanoesters were synthesized by first coupling commercially available carboxylic acids to 2-hydroxy-2-(2-methoxynaphthalen-6-yl)-acetonitrile using the wellknown coupling agent 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) [32] (Scheme 1, route B). Subsequent epoxidation of the resulting α-cyanoester was accomplished with m-CPBA.…”

Section: Design and Synthesismentioning

confidence: 99%

Fluorescent substrates for soluble epoxide hydrolase and application to inhibition studies

Jones

Wolf

Morisseau

et al. 2005

Analytical Biochemistry

149

233

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Inhibition of the mammalian soluble epoxide hydrolase (sEH) is a promising new therapy in the treatment of disorders resulting from hypertension and vascular inflammation. A spectrophotometric assay (4-nitrophenyl-trans-2,3-epoxy-3-phenylpropyl carbonate, NEPC) is currently used to screen libraries of chemicals; however this assay lacks the required sensitivity to differentiate the most potent inhibitors. A series of fluorescent α-cyanoester and α-cyanocarbonate epoxides that produce a strong fluorescent signal on epoxide hydrolysis by both human and murine sEH were designed as potential substrates for an in vitro inhibition assay. The murine enzyme showed a broad range of specificities, whereas the human enzyme showed the highest specificity for cyano(6-methoxynaphthalen-2-yl)methyl trans- [(3-phenyloxiran-2-yl) methyl] carbonate. An in vitro inhibition assay was developed using this substrate and recombinant enzyme. The utility of the fluorescent assay was confirmed by determining the IC 50 values for a series of known inhibitors. The new IC 50 values were compared with those determined by spectrophotometric NEPC and radioactive tDPPO assays. The fluorescent assay ranked these inhibitors on the basis of IC 50 values, whereas the NEPC assay did not. The ranking of inhibitor potency generally agreed with that determined using the tDPPO assay. These results show that the fluorescence-based assay is a valuable tool in the development of sEH inhibitors by revealing structure-activity relationships that previously were seen only by using the costly and labor-intensive radioactive tDPPO assay. KeywordsSoluble epoxide hydrolase; α-Cyanoester; α-Cyanocarbonate; Kinetic assay; Fluorescent substrateThe soluble epoxide hydrolase (sEH, EC 3.3.2.3) 1 is a member of the α/β-hydrolase fold family of enzymes [1] and catalyzes the hydrolysis of an epoxide to its corresponding diol through the catalytic addition of a water molecule [2]. The endogenous substrates for the sEH include epoxides of arachidonic acid [3,4] and linoleic acid [5,6]. Arachidonic acid epoxides (epoxyeicosatrienoic acid epoxides, EETs) are known modulators of blood pressure [7,8] and vascular permeability [9,10]. It has been shown that sEH inhibition not only lowers blood * Corresponding author. Fax: +1 530 752 1537. E-mail address:bdhammock@ucdavis.edu (B.D. Hammock).. 1 Abbreviations used: sEH, soluble epoxide hydrolase; EET, epoxyeicosatrienoic acid epoxides; NEPC, 4-nitrophenyl-trans-2,3-epoxy-3-phenylpropyl carbonate; TEA, triethylamine; TLC, thin-layer chromatography; TMS, tetramethylsilane; ppm, parts per million; oa-TOF, orthogonal acceleration time-of-flight; THF, tetrahydrofuran; m-CPBA, m-chloroperbenzoic acid; BSA, bovine serum albumin; RFU, relative fluorescent units; OD, optical density; DMSO, dimethyl sulfoxide; EDCI, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; tDPPO, [ 3 H] pressure in rodent models but also offers protection against hypertension-related renal damage [4,11,12].For the past 6 years, we have investi...

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“…For the N-acylation of sphingosine, various means of carboxyl activation were evaluated, including N-hydroxysuccinimide, carbodiimides, 4-nitrophenyl esters, ethylchloroformate and dimethylsulfamoyl chloride. The best yields and easiest purification were achieved with succinimidyl esters of the correspondent carboxylic acids [32] , except for ceramide 12/2, which was synthesized via carbodiimide coupling [33] . The synthetic scheme and the list of the prepared compounds are shown in figure 1 .…”

Section: Synthesismentioning

confidence: 99%

Short-Chain Ceramides Decrease Skin Barrier Properties

Novotný¹,

Janůšová²,

Novotný³

et al. 2008

Skin Pharmacol Physiol

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Stratum corneum ceramides are major determinants of skin barrier function. Although their physiological and pathological role has been widely investigated, to date no structure-activity relationships have been established. In this study, a series of short-chain ceramide analogues with polar head structure identical to ceramide NS, a sphingosine length of 12 carbons and an acyl chain length of 2–12 carbons was synthesized. Their effect on skin permeability was evaluated using porcine skin and two model drugs, theophylline and indomethacin, and compared to that of a physiological ceramide NS. The results showed that the ceramide chain length was crucial for their barrier properties. Ceramides with a 4- to 8-carbon acyl chain were able to increase skin permeability for both drugs up to 10.8 times with maximum effect at a 6-carbon acyl chain. No increase in permeability was found for ceramide analogues with 2- and 12-carbon acyl chains and ceramide NS. The same relationships were obtained for skin concentrations of the model drugs. The relationship between ceramide acyl chain length and its ability to perturb skin barrier showed striking similarity to the behavior of short-chain ceramides in sphingomyelin/phospholipid membranes and confirmed that short-chain ceramides do not act as natural ceramides and their use as experimental tools should be cautious.

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Esterification of N-protected .alpha.-amino acids with alcohol/carbodiimide/4-(dimethylamino)pyridine. Racemization of aspartic and glutamic acid derivatives

Cited by 202 publications

References 0 publications

Enzymatic transesterification of monosaccharides and amino acid esters in organic solvents

Enzymatic transesterification of monosaccharides and amino acid esters in organic solvents

Fluorescent substrates for soluble epoxide hydrolase and application to inhibition studies

Short-Chain Ceramides Decrease Skin Barrier Properties

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