Academic literature on the topic '3–(trans–2–aminocyclopropyl)alanine'

The effects of amino acid sidechain length, substituent position and c chirality on amino acid/K+ symport have been examined in rapid filtration experiments on brush-border membrane vesicles prepared from larval Manduca sexta midgut. Cis-inhibition and trans-stimulation protocols were used to examine the effects of amino acid analogs on the uptake of alanine, phenylalanine, leucine and lysine, which are cotransported with K+ by a zwitterionic symporter at the high pH characteristic of the midgut in vivo. The symporter was found to translocate both L- and D-stereoisomers of alanine, leucine and lysine, but only the L-form of phenylalanine. Alterations to substrate structure that leave the charge distribution unchanged do not affect symport. Thus, moving the methyl group from C-3 to C-5 in the sequence isoleucine, leucine and norleucine has no effect on their ability to inhibit leucine symport. Increasing sidechain length among alanine homologs has little effect on their ability to inhibit alanine uptake, but increasing the sidechain length of lysine homologs from 1 to 3 methylene groups enhances cis-inhibition and trans-stimulation of lysine symport. The substantial difference in molecular charge distribution among aminobutanoic acid isomers has a large impact on alanine symport with only alpha- (or 2-) aminobutanoic acid functioning as an alanine analog. Only those changes in substrate structure that are coupled to the molecular charge distribution seem to affect symport. The tolerance of the symporter may reflect a balance mandated by the conflicting demands of selectivity and throughput.

Phytochemical investigation of the chloroform fraction obtained from Scrophularia hypericifolia aerial parts led to the isolation of nine acylated iridoid glycosides. The new compounds were identified as 6-O-α-L(2″-acetyl, 3″,4″-di-O-trans-cinnamoyl) rhamnopyranosyl-6′-acetyl catalpol (6′-acetyl hypericifolin A) (1), 6-O-α-L(2″, 4″-diacetyl, 3″-O-trans-cinnamoyl) rhamnopyranosyl-6′-acetyl catalpol (6′-acetyl hypericifolin B) (2), 6-O-α-L(2″-acetyl, 3″,4″-di-O-trans-cinnamoyl) rhamnopyranosyl catalpol (hypericifolin A) (3) and 6-O-α-L(2″, 4″-diacetyl, 3″-O-trans-cinnamoyl) rhamnopyranosyl catalpol (hypericifolin B) (4). Previously reported compounds were identified as laterioside (5), 8-O-acetylharpagide (6), 6-O-α-L(4′-O-trans-cinnamoyl) rhamnopyranosyl catalpol (7), lagotisoside D (8) and harpagoside (9). Identification achieved via analyses of physical and spectral data including 1D, 2D NMR and High Resolution Electrospray Ionization Mass spectroscopy (HRESIMS). Compounds 2–4 and 6 were subjected to biological evaluation against paracetamol-induced toxicity. The biochemical parameters aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) as well as total bilirubin were used to access the liver condition. Measurement of serum levels of urea, creatinine, sodium and potassium cations were indicators for kidney condition. Liver and kidney samples were subjected to histopathological study. The best protection was found in the group treated with 3 followed by 4 and 6, while 2 was almost inactive.

The reaction of the N-(diphenylmethylene) Schiff base from glycyl-L-prolyl-L-alanine methyl ester 1 with tetrachloropalladate in the presence of sodium acetate affords the orthopalladated bicyclic C ,N ,O chelate 2. Complex 2 was characterized by X-ray diffraction. Remarkably, the unit cell contains two independent molecules, the cis isomer 2a and the trans isomer 2b (referring to the peptide bond). 2 reacts with PPh3 by substitution of the carbonyl oxygen atom to give the C,N chelate 3.

Concentrative transfer of amino acids from mother to fetus is affected by transport across both microvillous (maternal-facing) and basal (fetal-facing) plasma membranes of the human placental syncytiotrophoblast. Isolated basal plasma membrane vesicles were used to elucidate transport systems for neutral amino acids across this membrane. The concentration dependence and inhibition of zero-trans-alanine uptake were studied and four pathways for alanine uptake were defined as follows: 1) a sodium-dependent system shared by methylaminoisobutyric acid, which has the characteristics of an A system; 2) a sodium-dependent system resistant to inhibition by methylaminoisobutyric acid, which has the characteristics of an ASC system; 3) a sodium-independent system which may resemble an L system; 4) nonsaturable uptake. The microvillous membrane of the syncytiotrophoblast possesses systems similar to 1 and 3, but system 2 is unique to the basal plasma membrane. Active and passive transport of amino acids across both microvillous and basal plasma membranes may contribute to trophoblast amino acid uptake and nutrition and to the transfer of amino acids to the fetus.

Ce mémoire présente trois approches différentes vers la synthèse du 3–(trans–2–nitrocyclopropyl)alanine, un intermédiaire synthétique de la hormaomycine. Cette molécule naturelle démontre d’intéressantes activités biologiques et pharmacologiques. Il est intéressant de souligner que ce dérivé donne facilement accès au 3–(trans–2–aminocyclopropyl)alanine, unité centrale de la bélactosine A. Ce composé naturel possédant lui aussi d’intéressantes propriétés biologiques, plusieurs études relationnelles structures-activités menant à des dérivés plus actifs de cette molécule ont été entreprises, démontrant l’intérêt toujours présent de synthétiser de façon efficace et optimale ces dérivés cyclopropaniques. Une méthodologie développée au sein de notre groupe de recherche et basée sur une réaction de cyclopropanation intramoléculaire diastéréosélective sera mise à profit afin d’élaborer une nouvelle voie de synthèse aussi élégante qu’efficace à la construction du 3–(trans–2–nitrocyclopropyl) alanine. En utilisant un carbène de rhodium généré soit par la dégradation d’un dérivé diazoïque, soit par la formation d’un réactif de type ylure d’iodonium, une réaction de cyclopropanation diastéréosélective permettra la formation de deux autres centres contigus et ce, sans même utiliser d’auxiliaire ou de catalyseur énantioenrichis. Ensuite, un réarrangement intramoléculaire précédant deux réactions synchronisées d’ouverture de cycle et de décarboxylation permettront l’obtention du composé d’intérêt avec un rendement global convenable et en relativement peu d’étapes. De cette manière, la synthèse formelle de la bélactosine A et de l’hormaomycine a été effectuée. Cette synthèse se démarque des autres par l’utilisation d’une seule transformation catalytique énantiosélective.
This master’s thesis presents three different approaches toward the synthesis of 3–(trans–2–nitrocyclopropyl)alanine, a key constituent of the natural product hormaomycin. This unusual compound demonstrates interesting biological and pharmaceutical activity. It is noteworthy that this unique amino acid can be readily converted to the corresponding 3–(trans–2–aminocyclopropyl)alanine, the central core of belactosin A, a natural compound exhibiting interesting biological properties. Efficient syntheses of these aminocyclopropane derivatives are of current interest since several structure-activity relationships in syntheses of belactosin A and hormaomycin analogues are currently under study in an effort to discover enhanced biological activity. A methodology developed in our research group based on a diastereoselective intramolecular cyclopropanation reaction will be used to elaborate a unique and elegant pathway to the synthesis of the 3–(trans–2–nitrocyclopropyl)alanine. By using a rhodium carbene generated either by the degradation of a diazoic derivative or by the formation of the corresponding iodonium ylide, a diastereoselective cyclopropanation reaction can be applied in the concerted elaboration of two chiral centers needed in the desired aminocyclopropanes, avoiding in this way the utilisation of chiral reagents. Following this key sequence, an intramolecular rearrangement followed by synchronous ring–opening/decarboxylation reactions will permit a convenient formation of the desired product in an acceptable overall yield and in few ensuing steps. In this manner, the formal synthesis of the hormaomycin and the belactosin A can be achieved. This synthesis is unique since it involves only one asymmetric step in the whole synthetic process.