[reaction: see text] A new synthesis of stereodefined aziridines and azetidines, starting from 4-(1- or 2-haloalkyl)azetidin-2-ones, is described. Treatment of the latter compounds with LiAlH(4) gave 1,2-fission of the beta-lactam, followed by an intramolecular nucleophilic substitution of the halogen, giving rise to the formation of 2-(1-alkoxy-2-hydroxyethyl)aziridines in the case of 4-(1-haloalkyl)azetidin-2-ones and of 2-(1-alkoxy-2-hydroxyethyl)azetidines in the case of 4-(2-haloalkyl)azetidin-2-ones. The resulting 2-(1-alkoxy-2-hydroxyethyl)aziridines were transformed into the corresponding trans-3,4-substituted oxolanes via an intramolecular nucleophilic ring opening, triggered by AlCl(3).
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/ol053015g | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Solvent Controlled Chemodivergent Sulfonyl Addition into Enynones: Synthesis of α-Furyl Sulfones and Stereodefined Vinyl Sulfones.
J Org Chem
January 2025
Department of Chemistry, National Institute of Technology, Tiruchirappalli 620015, Tamilnadu, India.
Sodium salt of aryl sulfinic acid reacts with enynone in a different manner, yielding α-furyl sulfone and stereodefined vinyl sulfone in toluene and EtOH respectively in the presence of ZnCl. The salient features of this protocol include chemoselectivity, broad substrate scope, high efficiency, high yield, and easy purification. The synthetic utilities of the products are demonstrated by cycloaddition and cis-trans photoisomerization reactions.
View Article and Find Full Text PDFGeneral Alkene 1,2--Cyano-Hydroxylation Procedure Via Electrochemical Activation of Isoxazoline Cycloadducts.
J Am Chem Soc
November 2024
Department of Chemistry, The University of Manchester, Oxford Road, Manchester M13 9PL, U.K.
Stereoselective alkene 1,2-difunctionalization is a privileged strategy to access three-dimensional C(sp)-rich chiral molecules from readily available "flat" carbon feedstocks. State-of-the-art approaches exploit chiral transition metal-catalysts to enable high levels of regio- and stereocontrol. However, this is often achieved at the expense of a limited alkene scope and reduced generality.
View Article and Find Full Text PDFPoly-Dha Sequences as -polypeptides: An Original Mechanistic Postulate Leads to the Discovery of a Long-Acting Vasodilator KU04212.
JACS Au
October 2024
Department of Medicinal Chemistry, University of Kansas, Lawrence, Kansas 66045, United States.
The construction of polypeptides was revolutionized by Merrifield's solid-phase synthesis more than half a century ago. Herein, we explore a completely different approach to making peptides. We test an original mechanistic postulate wherein a single peptide made entirely of dehydroalanine (Dha) residues can give rise to regio- and stereodefined peptides by iterative conjugate addition of one- or two-electron nucleophiles.
View Article and Find Full Text PDFP-Stereodefined morpholino dinucleoside 3',5'-phosphorothioates.
Org Biomol Chem
November 2024
Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department of Bioorganic Chemistry, Sienkiewicza 112, 90-363 Łódź, Poland.
Here, we present for the first time the synthesis of P-stereodefined morpholino phosphorothioate analogs by using a modified 1,3,2-oxathiaphospholane method (OTP method) and provide valuable structural insights into their stereochemistry. -(2-Thio-4,4-pentamethylene-1,3,2-oxathiaphospholane) derivatives of morpholino-type nucleosides (U-OTPs) were synthesized, separated into pure P-diastereomers and used to prepare P-stereodefined morpholino dinucleoside 3',5'-phosphorothioates.
View Article and Find Full Text PDFThe beauty of symmetry: siRNA phosphorodithioate modifications reduce stereocomplexity, ease analysis, and can improve potency.
Mol Ther Nucleic Acids
December 2024
Silence Therapeutics GmbH, Robert-Rössle-Street 10, 13125 Berlin, Germany.
Phosphorothioates (PSs) can be essential in stabilizing therapeutic oligonucleotides against enzymatic degradation. However, unless synthesis is performed with stereodefined amidites, each PS introduces a chemically undefined stereocenter, resulting in 2 unique molecules in the final product and affecting downstream analytics and purification. Replacing the second non-bridging oxygen with sulfur results in phosphorodithioate (PS2) linkages, thereby removing the stereocenter.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!