68-95-1Relevant articles and documents
n-Pentyl N-acetylprolinate. A new skin penetration enhancer
Harris,Tenjarla,Holbrook,Smith,Mead,Entrekin
, p. 640 - 642 (1995)
The activity of n-pentyl N-acetylprolinate (PNAP) as a transdermal penetration enhancer was investigated. PNAP was synthesized from L-proline by acetylation with acetic anhydride, followed by acid-catalyzed esterification with 1-pentanol. Structure confirmation was accomplished by IR and NMR spectroscopy and elemental analysis. Benzoic acid (BA) was used as a model drug, and the effect of PNAP on the flux of BA through human cadaver skin was evaluated. The central nervous system (CNS) toxicity of PNAP was evaluated by comparing the effects of intraperitoneal administration of PNAP to mice with those of laurocapram (Azone), a known penetration enhancer. Based on preliminary studies, PNAP appears to be an effective transdermal penetration enhancer, is nontoxic at tow doses, and exhibits dose-related CNS toxicity at higher doses.
Bacterial Alkaloids Prevent Amoebal Predation
Klapper, Martin,G?tze, Sebastian,Barnett, Robert,Willing, Karsten,Stallforth, Pierre
, p. 8944 - 8947 (2016)
Bacterial defense mechanisms have evolved to protect bacteria against predation by nematodes, predatory bacteria, or amoebae. We identified novel bacterial alkaloids (pyreudiones A–D) that protect the producer, Pseudomonas fluorescens HKI0770, against amoebal predation. Isolation, structure elucidation, total synthesis, and a proposed biosynthetic pathway for these structures are presented. The generation of P. fluorescens gene-deletion mutants unable to produce pyreudiones rendered the bacterium edible to a variety of soil-dwelling amoebae.
Bioinspired Synthesis of (?)-PF-1018
Houk, K. N.,Jamieson, Cooper S.,Quintela-Varela, Hugo,Shao, Qianzhen,Trauner, Dirk
supporting information, p. 5263 - 5267 (2020/02/11)
The combination of electrocyclizations and cycloadditions accounts for the formation of a range of fascinating natural products. Cascades consisting of 8π electrocyclizations followed by a 6π electrocyclization and a cycloaddition are relatively common. We now report the synthesis of the tetramic acid PF-1018 through an 8π electrocyclization, the product of which is immediately intercepted by a Diels–Alder cycloaddition. The success of this pericyclic cascade was critically dependent on the substitution pattern of the starting polyene and could be rationalized through DFT calculations. The completion of the synthesis required the instalment of a trisubstituted double bond by radical deoxygenation. An unexpected side product formed through 4-exo-trig radical cyclization could be recycled through an unprecedented triflation/fragmentation.
The effect of imidazolium salts with amino acids as counterions on the reactivity of 4-nitrophenyl acetate: A kinetic study
Figueroa, Roberto,Orth, Elisa,Pavez, Paulina,Rojas, Mabel,Santos, José G.
, (2020/04/29)
As a first approach to improve the “green character” of the surfactants based on imidazolium cations, three surfactants using 1-tetradecyl-3-methylimidazolium [C14mim]+ as cation and different amino acids (AA) as counterion, were syn
Synthesis method of L-prolinamide
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Paragraph 0030; 0031; 0035; 0036; 0040; 0041; 0045; 0046, (2019/01/16)
The invention belongs to the field of organic synthesis, and discloses a synthesis method of L-prolinamide. The method comprises steps of S1, dissolving an initial material, L-proline, in water and then reacting with acetic anhydride, after reaction, extracting and drying to prepare N-acetyl-L-proline; S2, in a solvent system, performing a reaction on a raw material, N-acetyl-L-proline prepared inS1 and thionyl chloride, then concentrating and drying to obtain a compound; S3, dripping aqueous ammonia in the compound prepared in S2 as a raw material so as to react, filtering and preparing 1-acetyl-2-pyrrolidinecarboxamide; and S4, dripping HC1 into the 1-acetyl-2-pyrrolidinecarboxamide prepared in S3 as a raw material, so as to react, then concentrating, filtering and drying to prepare L-prolinamide. In the reaction process of the synthesis method provided by the invention, common reagent raw materials are used, the costs are low, the reaction conditions are mild, the chiral purity ishigh, the yield is high, the environment pressure is low, and the synthesis method is suitable for large-scale production.
(4-HYDROXYPYRROLIDIN-2-YL)-HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF
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Paragraph 0710; 0711; 0712, (2019/05/15)
The present disclosure relates to bifunctional compounds of formula (I), which can be used as modulators of targeted ubiquitination. In particular, the present disclosure is directed to compounds which contain on one end a VHL ligand moiety, which binds to the VHL E3 ubiquitin ligase, and on the other end a moiety that binds a target protein such that degradation of the target protein/polypeptide is effectuated. Also disclosed are VHL ligands of formula (III).
Reactivity of α-Amino Acids in the Reaction with Esters in Aqueous–1,4-Dioxane Media
Kochetova,Kustova,Kuritsyn
, p. 80 - 85 (2018/03/09)
The kinetics of the reaction of a series of α-amino acids with 4-nitrophenyl acetate, 4-nitrophenyl benzoate, and 2,4,6-trinitrophenyl benzoate in aqueous 1,4-dioxane medium has been studied. Kinetics of the reactions involving 4-nitrophenyl acetate and 2,4,6-trinitrophenyl benzoate has complied with the Br?nsted dependence and revealed linear correlation between rate constant logarithm and the energy difference of the frontier orbitals of α-amino acids anions.
Cinnamic acid derivative with aldose reductase inhibitory activity as well as preparation method and application thereof
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Paragraph 0087; 0091, (2017/09/01)
The invention discloses a cinnamic acid derivative with aldose reductase inhibitory activity, a preparation method thereof and an application of the cinnamic acid derivative in preparation of a medicine used for treating diabetic complications and diseases caused by oxidative stress. The structure of the compound is shown in a formula I. The preparation method comprises the following steps: firstly reacting substituted benzaldehyde with substituted acetic acid or acid anhydride thereof to obtain substituted cinnamic acid, then reacting with a diamine compound protected by N-tertiary butoxy acyl to obtain substituted cinnamoyl diamide protected by N-tertiary butoxy acyl; and carrying out tertiary butoxy acyl deprotection on the substituted cinnamoyl diamide protected by N-tertiary butoxy acyl, and then reacting with natural or non-natural N-acyl alpha-amino acid, so that the cinnamic acid derivative is obtained. The cinnamic acid derivative compound disclosed by the invention has excellent inhibitory activity on aldose reductase and excellent antioxidant activity and can be applied to preparation of a medicine used for treating the diabetic complications, especially diabetic retinopathy, senile dementia due to diabetes and nerve ending disturbance, as well as diseases caused by the oxidative stress.
Modulating hydrogen-bond basicity within the context of protein-ligand binding: A case study with thrombin inhibitors that?reveals a dominating role for desolvation
Nasief, Nader N.,Said, Ahmed M.,Hangauer, David
, p. 975 - 991 (2016/11/11)
Understanding subtle aspects of hydrogen bonding is a challenging but crucial task to improve our ability to design ligands with high affinity for protein hosts. To gain a deeper understanding of these aspects, we investigated a series of thrombin inhibitors in which the basicity of the ligand's group that accepts an H-bond from Gly216 was modulated via bioisosterism; e.g., a C=O acceptor was made electron deficient or rich via bioisosteric replacements of the adjacent moiety. Although the ligand's binding affinity was anticipated to improve when the H-bond basicity is increased (due to stronger H-bonding with the protein), we herein present data that unexpectedly revealed an opposite trend. This trend was attributed to a dominating role played by desolvation in determining the relative binding affinity. For example, a decrease in the H-bond basicity reduces the desolvation penalty and, as experimentally observed, improves the binding affinity, given that the reduction in the desolvation penalty dominates the change in the net contribution of the ligand's interactions with the protein. The current study, therefore, reveals that desolvation can be a major underlying cause for the apparently counterintuitive structure-activity relationship (SAR) outcomes, and indicates that understanding this factor can improve our ability to predict binding affinity and to design more potent ligands.
Energetic contribution to both acidity and conformational stability in peptide models
Kubyshkin, Vladimir,Durkin, Patrick,Budisa, Nediljko
supporting information, p. 5209 - 5220 (2016/07/06)
The acidity of N-acyl amino acids is dependent upon the rotameric state of the amide bond. In this work we systematically investigated the acidity difference of the rotamers (ΔpKa) in the frames of various acetylated amino acids. Our results indicated a mutual interaction of two carbonyl groups of an attractive type. We observed conservative ΔpKas for acyclic amino acids (2.2-3.0 kJ mol-1), whereas in the case of alicyclic amino acids, the experimental values revealed a strong dependency on the structural context (1.5-4.4 kJ mol-1). In homologous amino acids (α-, β-, γ-, etc.), the strength of the attraction decays in an exponential fashion. Furthermore, the interaction can accumulate through a chain of amide bonds in a cascade fashion, as demonstrated by an Ac-Pro-Pro dipeptide. As a result, we demonstrate that ΔpKa is an experimental parameter to estimate increments in the carbonyl-carbonyl alignment, as determined by the amino acid or peptidyl context. This parameter is also important in understanding the roles of amino acids in both protein folding and translation in biological systems as well as their evolutionary appearance in the genetic code.
