41088-89-5Relevant articles and documents
Primary amino acid derivatives: Compounds with anticonvulsant and neuropathic pain protection activities
King, Amber M.,Salomé, Christophe,Dinsmore, Jason,Salomé-Grosjean, Elise,De Ryck, Marc,Kaminski, Rafal,Valade, Anne,Kohn, Harold
supporting information; experimental part, p. 4815 - 4830 (2011/10/01)
Pharmacological management remains the primary method to treat epilepsy and neuropathic pain. We have advanced a novel class of anticonvulsants termed functionalized amino acids (FAAs). In this study, we examine FAA derivatives from which the terminal acetyl moiety was removed and termed these compounds primary amino acid derivatives (PAADs). Twenty-seven PAADs were prepared; the central C(2) R-substituent was varied, including C(2) stereochemistry, and the compounds were tested in rodent models of seizures and neuropathic pain. C(2)-Hydrocarbon N-benzylamide PAADs were potent anticonvulsants and excellent anticonvulsant activity (mice, ip; rat, po) was observed for C(2) R-substituted PAADs in which the R group was ethyl, isopropyl, or tert-butyl, and the C(2) stereochemistry conformed to the d-amino acid configuration ((R)-stereoisomer). These values surpassed the activities of several clinical antiepileptic drugs. The C(2) (R)-ethyl and C(2) (R)-isopropyl PAADs also displayed excellent activities in the mouse (ip) formalin neuropathic pain model. Significantly, unlike the FAA structure-activity relationship, PAAD anticonvulsant activity increased upon substitution of a methylene unit for a heteroatom in the R-substituent that was one atom removed from the C(2) site, suggesting that these PAADs function by a different pathway than FAAs.
Cyclic hydroxamates, especially multiply substituted [1,2]oxazinan-3-ones
Wolfe, Saul,Wilson, Marie-Claire,Cheng, Ming-Huei,Shustov, Gennady V.,Akuche, Christiana I.
, p. 937 - 960 (2007/10/03)
Routes to putative N-acyl-D-ala-D-ala surrogates, beginning with the conversion of 4-, 5-, and 6-membered lactones into 5-, 6-, and 7-membered cyclic hydroxamates, are reported. The key step of the synthesis is trimethylaluminium-promoted cyclization of an ω-aminooxyester. The 7-membered cyclic hydroxamate crystallizes in a chair conformation. Extension of the reaction sequence to homoserine or homoserine lactone leads to cyclocanaline and N-acylated cyclocanalines. The 4-phenylacetamido derivative of cyclocanaline crystallizes in a boat conformation. The attachment of a 2-carboxypropyl substituent to the ring nitrogen of a 4-acylaminocyclocanaline has been effected, prior to cyclization, by coupling of the acyclic aminooxyester precursor to the triflate of benzyl lactate or, after cyclization, by coupling to tert-butyl α-bromopropionate in the presence of potassium fluoride - alumina, followed by removal of the protecting group in each case. A six-membered homolog of the antibiotic lactivicin has been synthesized by the reaction of 4-phenylacetamidocyclocanaline with benzyl 2-oxoglutarate in the presence of carbodiimide, followed by hydrogenolysis. Starting with methyl 2,4-dibromo-2,4-dideoxy-L-erythronate, which is available in two steps from L-ascorbic acid, these reaction sequences have been applied to the stereospecific synthesis of a D-alanine derivative whose nitrogen atom is enclosed within a 3,4-disubstituted [1,2]oxazinan-3-one.
Insecticidal Properties of Some Derivatives of L-Canavanine
Rosenthal, Gerald A.,Dahlman, D. L.,Crooks, Peter A.,Phuket, Supinan Na,Trifonov, L. S.
, p. 2728 - 2734 (2007/10/03)
The canavanine derivatives D-canavanine and L-homocanavanine as well as the 1-methyl and 1-ethyl esters of L-canavanine were synthesized and evaluated for biological activity in fifth instar larvae of the tobacco hornworm, Manduca sexta .While L-homocanavanine did not increase intrinsic toxicity, it was as deleterious as L-canavanine.D-Canavanine was biologically active, as demonstrated by its ability to cause larval edema, but the D-enantiomer had little ability to elicit the larval growth inhibition and pupal deformity which are hallmarks of canavanine toxicosis and was postulated to be linked to aberrant protein production.The 1-methyl and 1-ethyl esters of L-canavanine were synthesized to determine if enhancing canavanine's hydrophobicity might increase its bioavailability.Our experiments revealed that these esters are less toxic than canavanine; the ethyl ester disrupted larval growth more than did the methyl analogue. - Keywords: L-Canavanine; D-canavanine; L-homocanavanine; 1-methyl-L-canavanine; 1-ethyl-L-canavanine; Manduca sexta
