1. Efficient Fmoc-Protected Amino Ester Hydrolysis Using Green Calcium(II) Iodide as a Protective Agent
Renaud Binette, Michael Desgagné, Camille Theaud, Pierre-Luc Boudreault Molecules. 2022 Apr 27;27(9):2788. doi: 10.3390/molecules27092788.
In order to modify amino acids, the C-terminus carboxylic acid usually needs to be protected, typically as a methyl ester. However, standard cleavage of methyl esters requires either highly basic or acidic conditions, which are not compatible with Fmoc or acid-labile protecting groups. This highlights the need for orthogonal conditions that permit selective deprotection of esters to create SPPS-ready amino acids. Herein, mild orthogonal ester hydrolysis conditions are systematically explored using calcium(II) iodide as a protective agent for the Fmoc protecting group and optimized for a broad scope of amino esters. Our optimized reaction improved on the already known trimethyltin hydroxide, as it produced better yields with greener, inexpensive chemicals and a less extensive energy expenditure.
2. A Ketone Ester Drink Lowers Human Ghrelin and Appetite
Brianna J Stubbs, Pete J Cox, Rhys D Evans, Malgorzata Cyranka, Kieran Clarke, Heidi de Wet Obesity (Silver Spring). 2018 Feb;26(2):269-273. doi: 10.1002/oby.22051. Epub 2017 Nov 6.
Objective: The ketones d-β-hydroxybutyrate (BHB) and acetoacetate are elevated during prolonged fasting or during a "ketogenic" diet. Although weight loss on a ketogenic diet may be associated with decreased appetite and altered gut hormone levels, it is unknown whether such changes are caused by elevated blood ketones. This study investigated the effects of an exogenous ketone ester (KE) on appetite. Methods: Following an overnight fast, subjects with normal weight (n = 15) consumed 1.9 kcal/kg of KE, or isocaloric dextrose (DEXT), in drinks matched for volume, taste, tonicity, and color. Blood samples were analyzed for BHB, glucose, insulin, ghrelin, glucagon-like peptide 1 (GLP-1), and peptide tyrosine tyrosine (PYY), and a three-measure visual analogue scale was used to measure hunger, fullness, and desire to eat. Results: KE consumption increased blood BHB levels from 0.2 to 3.3 mM after 60 minutes. DEXT consumption increased plasma glucose levels between 30 and 60 minutes. Postprandial plasma insulin, ghrelin, GLP-1, and PYY levels were significantly lower 2 to 4 hours after KE consumption, compared with DEXT consumption. Temporally related to the observed suppression of ghrelin, reported hunger and desire to eat were also significantly suppressed 1.5 hours after consumption of KE, compared with consumption of DEXT. Conclusions: Increased blood ketone levels may directly suppress appetite, as KE drinks lowered plasma ghrelin levels, perceived hunger, and desire to eat.
3. Palladium-Catalyzed Tandem Ester Dance/Decarbonylative Coupling Reactions
Masayuki Kubo, Naomi Inayama, Eisuke Ota, Junichiro Yamaguchi Org Lett. 2022 Jun 3;24(21):3855-3860. doi: 10.1021/acs.orglett.2c01432. Epub 2022 May 23.
"Dance reaction" on the aromatic ring is a powerful method in organic chemistry to translocate functional groups on arene scaffolds. Notably, dance reactions of halides and pseudohalides offer a unique platform for the divergent synthesis of substituted (hetero)aromatic compounds when combined with transition-metal-catalyzed coupling reactions. Herein, we report a tandem reaction of ester dance and decarbonylative coupling enabled by palladium catalysis. In this reaction, 1,2-translocation of the ester moiety on the aromatic ring is followed by decarbonylative coupling with nucleophiles to enable the installation of a variety of nucleophiles at the position adjacent to the ester in the starting material.
