92645-20-0Relevant academic research and scientific papers
Backbone amide linker (BAL) strategy for N(α)-9- fluorenylmethoxycarbonyl (Fmoc) solid-phase synthesis of unprotected peptide p-nitroanilides and thioesters
Alsina, Jordi,Yokum, T. Scott,Albericio, Fernando,Barany, George
, p. 8761 - 8769 (1999)
A novel and general backbone amide linker (BAL) strategy has been devised for preparation of C-terminal modified peptides containing hindered, unreactive, and/or sensitive moieties, in concert with N(α)-9- fluorenylmethoxycarbonyl (Fmoc) solid-phase synthesis protocols. This strategy comprises (i) start of peptide synthesis by anchoring the penultimate residue, with its carboxyl group orthogonally protected, through the backbone nitrogen, (ii) continuation with standard protocols for peptide chain elongation in the C→N direction, (iii) selective orthogonal removal of the carboxyl protecting group, (iv) solid-phase activation of the pendant carboxyl and coupling with the desired C-terminal residue, and (v) final cleavage/deprotection to release the free peptide product into solution. To illustrate this approach, several model peptide p-nitroanilides and thioesters have been prepared in excellent yields and purifies, with minimal racemization. Such compounds are very difficult to prepare by standard Fmoc chemistry, including the BAL strategy as originally envisaged.
Ynamide-Mediated Thioester Synthesis
Wang, Xuewei,Zhao, Yongli,Yang, Jinhua,Li, Yanxi,Luo, Ying,Xu, Mengyao,Zhao, Junfeng
, p. 18265 - 18277 (2021/12/17)
A novel ynamide-mediated thioester synthesis strategy was developed. Importantly, no detectable racemization was observed for the thioesterifications of carboxylic acids containing an α-chiral center, enabling it to be useful for the synthesis of peptide thioester, which is the key component of native chemical ligation. It is worth mentioning that amino acid side chain functional groups such as -OH and indole -NH are compatible with the reaction conditions, rendering their protection unnecessary. Moreover, this method was also amenable to selenoesters.
Application of dehydroalanine as a building block for the synthesis of selenocysteine-containing peptides
Reddy, Kishorkumar M.,Mugesh, Govindasamy
, p. 34 - 43 (2019/01/16)
Selenocysteine (Sec), the 21st proteinogenic amino acid, is inserted co-translationally into number of natural proteins. It is coded by a dual function stop codon UGA (opal). It is a redox active amino acid found at the active sites of several
Enantioselective Synthesis of Quaternary Δ4- and Δ5-Dehydroprolines Based on a Two-Step Formal [3+2] Cycloaddition of α-Aryl and α-Alkyl Isocyano(thio)acetates with Vinyl Ketones
Odriozola, Amaiur,Oiarbide, Mikel,Palomo, Claudio
supporting information, p. 12758 - 12762 (2017/09/25)
A divergent synthesis of optically active quaternary Δ4- and Δ5-dehydro prolines is developed based on the first catalytic enantioselective conjugate addition of α-substituted isocyano(thio)acetates to vinyl ketones that is general for both α-aryl and α-alkyl isocyano(thio)acetates. The new tetrasubstituted C?N stereocenter is formed without the need of any metal salt due to a bifunctional tertiary amine/squaramide catalyst, featuring a bulky polyaryl sidearm and an unusually short squaramide diamide H???H interatomic distance in the solid state.
Visible-Light-Mediated Selective Arylation of Cysteine in Batch and Flow
Bottecchia, Cecilia,Rubens, Maarten,Gunnoo, Smita B.,Hessel, Volker,Madder, Annemieke,No?l, Timothy
supporting information, p. 12702 - 12707 (2017/09/08)
A mild visible-light-mediated strategy for cysteine arylation is presented. The method relies on the use of eosin Y as a metal-free photocatalyst and aryldiazonium salts as arylating agents. The reaction can be significantly accelerated in a microflow reactor, whilst allowing the in situ formation of the required diazonium salts. The batch and flow protocol described herein can be applied to obtain a broad series of arylated cysteine derivatives and arylated cysteine-containing dipeptides. Moreover, the method was applied to the chemoselective arylation of a model peptide in biocompatible reaction conditions (room temperature, phosphate-buffered saline (PBS) buffer) within a short reaction time.
Native chemical ligation, thiol-ene click: A methodology for the synthesis of functionalized peptides
Markey, Lyn,Giordani, Silvia,Scanlan, Eoin M.
, p. 4270 - 4277 (2013/06/27)
The sequential combination of native chemical ligation and thiol-ene radical chemistry (NCL-TEC) on the resulting cysteine thiol has been investigated as a methodology for rapidly accessing functionalized peptides. Three sequential cycles of native chemical ligation and subsequent thiyl radical reactions (including a free-radical-mediated desulfurization reaction) were carried out on a peptide backbone demonstrating the iterative nature of this process. The versatility of the thiyl radical reaction at cysteine was demonstrated through the introduction of a number of different side chains including an amino acid derivative, a carbohydrate group, and an alkyl azide. Conditions were developed that allowed the sequential NCL-TEC process to proceed in high yield.
Novel synthesis and biological evaluation of enigmols as therapeutic agents for treating prostate cancer
Garnier-Amblard, Ethel C.,Mays, Suzanne G.,Arrendale, Richard F.,Baillie, Mark T.,Bushnev, Anatoliy S.,Culver, Deborah G.,Evers, Taylor J.,Holt, Jason J.,Howard, Randy B.,Liebeskind, Lanny S.,Menaldino, David S.,Natchus, Michael G.,Petros, John A.,Ramaraju, Harsha,Reddy, G. Prabhakar,Liotta, Dennis C.
supporting information; experimental part, p. 438 - 443 (2011/08/06)
Enigmol is a synthetic, orally active 1-deoxysphingoid base analogue that has demonstrated promising activity against prostate cancer. In these studies, the pharmacologic roles of stereochemistry and N-methylation in the structure of enigmols were examined. A novel enantioselective synthesis of all four possible 2S-diastereoisomers of enigmol (2-aminooctadecane-3,5-diols) from l-alanine is reported, which features a Liebeskind-Srogl cross-coupling reaction between l-alanine thiol ester and (E)-pentadec-1-enylboronic acid as the key step. In vitro biological evaluation of the four enigmol diastereoisomers and 2S,3S,5S-N-methylenigmol against two prostate cancer cell lines (PC-3 and LNCaP) indicates that all but one diastereomer demonstrate potent oncolytic activity. In nude mouse xenograft models of human prostate cancer, enigmol was equally effective as standard prostate cancer therapies (androgen deprivation or docetaxel), and two of the enigmol diastereomers, 2S,3S,5R-enigmol and 2S,3R,5S-enigmol, also caused statistically significant inhibition of tumor growth. A pharmacokinetic profile of enigmol and N-methylenigmol is also presented.
METHODS OF PREPARING 1-DEOXY-SPHINGOID BASES AND DERIVATIVES THEREOF
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Page/Page column 18, (2010/08/08)
Novel methods of synthesizing 1-deoxy-sphingoid bases and derivatives are disclosed. The synthesis is achieved from commercially available and inexpensive starting materials. The process includes thioesterification, cross-coupling, and reduction. The proc
