The development of a multigram synthesis of 3--isopropylbicyclo[2.2.1]heptan-2--amine hydrochloride () (also known as BRD4780 and AGN-192403) is described. The process involves protection of the amine as 4-nitrobenzyl carbamate, pNZ, which enables chiral SFC chromatography. The absolute configuration (AC) of the individual enantiomers has been determined by Mosher's amide method, VCD spectroscopy, and X-ray crystallography. We highlight the VCD approach as a rapid and effective means of AC determination that can be deployed directly on the target compounds.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.joc.0c02520 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Multigram Synthesis of 3,3-Spiro-α-prolines.
J Org Chem
December 2024
Enamine Ltd., 78 Winston Churchill Street, 02094 Kyiv, Ukraine.
A series of novel spirocyclic α-proline building blocks with a spiro conjunction in position 3 of the pyrrolidine ring was prepared to employ two convenient and practical synthetic approaches. Both alternative routes utilize simple and readily available starting materials─cyclic ketones and esters─and comprise 6 and 7 steps, respectively. The methodologies feature distinct advantages, using routine organic chemistry transformations, and are suitable for producing multigram amounts of the target prolines.
View Article and Find Full Text PDFA flexible and scalable synthesis of 4'-thionucleosides.
Chem Sci
December 2024
Department of Chemistry, Simon Fraser University Burnaby British Columbia V5A 1S6 Canada
4'-Thionucleosides (thNAs) are synthetic nucleoside analogues that have attracted attention as leads for drug discovery in oncology and virology. Here we report a thNA synthesis that relies on a scalable α-fluorination and aldol reaction of α-heteroaryl acetaldehydes followed by a streamlined process involving carbonyl reduction, mesylate formation and a double displacement reaction using NaSH. We demonstrate the multigram preparation of 4'-thio-5-methyluridine and highlight the production of purine and pyrimidine thNAs as well as C2'-modified thNAs.
View Article and Find Full Text PDF4-Azaspiro[2.3]hexane, an Overlooked Piperidine Isostere: Multigram Synthesis and Physicochemical and Structural Evaluation.
J Org Chem
December 2024
Enamine Ltd., Winston Churchill Street 78, Kyïv 02094, Ukraine.
An expedient approach to the synthesis of 4-azaspiro[2.3]hexane derivatives is described. The synthetic scheme consists of Tebbe olefination of -Boc-protected 2-azetidinone (including the first use of the deuterated Petasis reagent CpTi(CD) in the building block preparation) and cyclopropanation of the resulting intermediate.
View Article and Find Full Text PDFAdvanced enzymatic multigram-scale production of nucleotide sugars in a continuous fed-batch membrane reactor.
J Biotechnol
November 2024
Laboratory for Biomaterials, Institute of Biotechnology, and Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Pauwelsstraße 20, Aachen 52074, Germany. Electronic address:
Enzymatic production of nucleotide sugars on a multigram scale presents a challenge, as only a few processes have been reported for large-scale nucleotide sugar production. They rely primarily on batch synthesis and employ exceptional amounts of enzymes. This study introduces a novel approach for the multigram-scale production of nucleotide sugars with a continuous fed-batch membrane reactor.
View Article and Find Full Text PDFTriptycene derivatives are used extensively in supramolecular and materials chemistry, however, most are prepared using a multi-step synthesis involving the generation of a benzyne intermediate, which hinders production on a large scale. Inspired by the ease of the synthesis of resorcinarenes, we report the rapid and efficient preparation of triptycene-like 1,6,2',7'-tetrahydroxynaphthopleiadene directly from 2,7-dihydroxynaphthalene and phthalaldehyde. Structural characterisation confirms the novel bridged bicyclic framework, within which the planes of the single benzene ring and two naphthalene units are fixed at an angle of ∼120° relative to each other.
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!