This manuscript describes the development and implementation of a scalable additive system, consisting of a lanthanide salt and a solubilizing quaternary ammonium salt, to improve the yield and robustness of the addition of an organomagnesium reagent to a ribonolactone en route to remdesivir. This system was found to be generally applicable in enhancing other challenging organomagnesium additions to enolizable and hindered carbonyl-containing compounds.

The utility of 1,5,7-triazabicyclo[4.4.0]dec-5-ene as a reagent to facilitate efficient amide formation by reaction of an amine with an unactivated ester was demonstrated on pilot-plant scale as a key step in the synthesis of an H-PGDS inhibitor.

An enantiospecific 1,2-amine migration process through an aziridinium intermediate involving ring-opening with potassium phthalimide derivatives to produce precursors to drug candidates was developed. The precursor amine derivatives were readily available by epoxide opening of simple glycidyl ether derivatives. The regioselectivity of the process was shown to provide approximately 85% of the desired rearranged product with subsequent conversion to the desired drug candidate occurring with excellent purity. An alternative approach using the same glycidyl ether derivatives as starting materials that overcame this regiochemical limitation was subsequently demonstrated.

The synthesis and NMR characterizations of 1,2,3,6-tetra-O-benzoyl-4-deoxy-4-fluoro-β-d-galactopyranoside, the 4-deoxy-4-fluoro epimer of an intermediate in the synthesis of a drug substance, needed for use as a potential impurity standard and to confirm the stereoselectivity of a key fluorination step, are described.

Route selection, process development and large-scale preparation of selectively benzoylated and fluorinated D-glucopyranoses, required as glycosyl donors for the synthesis of the SGLT inhibitor SAR7226, are discussed.

The syn thesis of high specific activity tritium-labeled 4-(acetoxymethylnitro-samino)-1-(3-pyridyl)-1-butanone is reported. This compound was prepared by tritiation of 4-(acetoxymethylnitrosamino)-1-[3-(5-bromo)-pyridyl]-1-butanone (5-BrNNKOAc) in the presence of 10% Pd/C catalyst, yielding a product with a specific activity of 11.9 Ci/mmol. This pathway represents a major improvement over previously published methods. Copyright (C) 2001 John Wiley & Sons, Ltd.

The aggregation in dilute aqueous solutions of several omega-substituted single-chain quaternary ammonium surfactants has been studied by Krafft temperature and critical aggregation/micelle concentration measurements and by cryo-transmission electron microscopy: (16-carboxyhexadecyl)trimethylammonium bromide (1a); (16-methoxycarbonylhexadecyl)trimethylammonium bromide (1b); (17,18-dihydroxyoctadecyl)trimethylammonium bromide (1c). Octadecyltrimethylammonium bromide (2) was included for comparison. The aggregation of 1a was also studied by Raman spectroscopy. Surfactant 1a at pH 6.8 forms ribbonlike fibers with lengths of up to 1.2 mu m and cross sections of 3-4 nm x 12-16 nm; at pH 2.2, ribbon to rodlike fibers; and at pH 11.5, wormlike aggregates. Surfactants 1b and 1c at pH 6.8 form I-ed-shaped aggregates. The Raman spectroscopy results indicated that 1a is not in a fully extended conformation within its fibers at pH 6.8. Tentative structural models have been proposed for the aggregates of surfactants 1.

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTSynthesis and Characterization of Chain-Substituted PhosphocholinesDavid A. Jaeger, Witold Subotkowski, Jinkang Wang, Elzbieta Kubicz-Loring, and Hiraku ShinozakiView Author Information Department of Chemistry, University of Wyoming, Laramie, Wyoming 82071-3838 Cite this: Langmuir 1997, 13, 6, 1844–1849Publication Date (Web):March 19, 1997Publication History Received23 July 1996Revised3 October 1996Published online19 March 1997Published inissue 1 March 1997https://pubs.acs.org/doi/10.1021/la960732yhttps://doi.org/10.1021/la960732ybrief-reportACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views215Altmetric-Citations1LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Acyls,Chromatography,Differential scanning calorimetry,Substituents,Vesicles Get e-Alerts

The influence of 2-amino-3-phosphonopropionic acid (AP3), an antagonist of metabotropic glutamate receptors and its N-methyl analog (N-methyl AP3) on acquisition, consolidation and recall of information in a passive avoidance situation was tested. Both compounds improved three examined parameters. The significant effect of AP3 appeared at the icv dose of 12.5 micrograms per rat when its influence on acquisition and consolidation was tested, and at the icv dose of 100 micrograms when its influence on retrieval process was evaluated. The significant improvement of acquisition of information was observed at the icv dose of 50 micrograms per rat of N-methyl AP3, but significant facilitation of consolidation and retrieval processes appeared at the higher dose of 100 micrograms per rat. Significant improvement of performance in a passive avoidance situation persisted in all experiments to the highest used dose of both compounds, 250 micrograms.

The influence of 2-amino-3-phosphonopropionic acid (AP3) an antagonist of metabotropic glutamate receptors and its N-methyl analog (N-methyl AP3) on locomotor activity in the "open field" test, apomorphine stereotypy and haloperidol catalepsy were tested. Both compounds had not any influence on spontaneous crossings of squares, number of rearings and bar approaches in the "open field" test. AP3 and its N-methyl analog significantly enhanced apomorphine stereotypy at the intracerebroventricular (icv) doses of 100 and 200 micrograms per rat respectively. Although, both compounds significantly diminished haloperidol catalepsy at the icv doses of 50, 100 and 200 micrograms per rat. All observed effects of AP3 and N-methyl AP3 were dose independent. Methyl substitution at the N-position in AP3 did not change pharmacological properties of this compound i.e. its influence on behavior mainly dependent on dopaminergic systems.

C-14 KIE (kinetic isotope effects) were measured for the C-1, C-2, C-4, and C-6 positions in the rearrangement of 2-(trimethylsiloxy)- (1a) and 2-(methoxycarbonyl)-3-oxa-1,5-hexadiene (1b). The data, along with earlier C-4 and C-6 deuterium KIE, were fitted to Bebovib modeling calculations. The calculations show that in the transition structure (TS) for 1a 70-80% bond breaking and 20% of bond making occurs, whereas in the TS of 1b both bond breaking and bond making amount to 30-40%. Results for 1a and 1b are compared with earlier results for the parent compound, allyl vinyl ether.

Kinetic isotope effects (KIE) in the rearrangement of allyl vinyl ether (1, 3-oxa-1,5-hexadiene) to 4-pentenal (2) were measured for labeling with C-14 at the 2-, 4-, and 6-positions and with O-18 at the 3-position. BEBOVIB modeling calculations were applied successfully to the heavy-atom KIE and previously reported KIE for deuterium substitution at positions 4 and 6. From the calculations, it is deduced that the C4-O bond is 50-70% broken and the C1-C6 bond 10-30% formed in the transition structure. Further, there is strong coupling between the allyl and vinyloxy fragments, strong bonding within the allyl but relatively weak bonding within the vinyloxy fragment.

KIE were measured for 1-C-14- and 1,1'-C-13(2)-labeling in the acid-catalyzed rearrangement of hydrazobenzene (1) to benzidine (2) and diphenyline (3). Small KIE were found for forming 2, but none were found for the formation of 3. The results are consistent with concerted formation of 2 and nonconcerted formation of 3. KIE were remeasured for 4-C-14-, 4,4'-C-13(2-)-, and N-15,N-15'-labeling and were found to differ in magnitude from KIE reported earlier. The results are, nevertheless, consistent with the concerted formation of 2 and nonconcerted formation of 3. The differences in transition states for these two processes are discussed. Quantitative measurements of product distributions ave 85% 2 and 15% 3.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The kinetic isotope effects, kC-12/kC-14, for the rearrangements of allyl [1-C-14]phenyl ether and [beta-C-14]allyl phenyl ether have been measured: 1.0119 +/- 0.0009 and 1.0148 +/- 0.0005, respectively. These results, along with those reported earlier for O-18, 2-C-14, alpha-C-14, and gamma-C-14, represent the first complete kinetic isotope effect (KIE) description of a pericyclic system. Modeling calculations have been applied to the heavy-atom KIE and the previously reported deuterium KIE to define the transition structure of the rearrangement more explicitly. The calculations confirm our earlier description that the C(alpha)-O bond is 50-60% broken while the C(gamma)-C(ortho) bond is 10-20% formed and now provide significantly more insight to the dynamics of the rearrangement. Coupling between the phenoxy and allyl fragments is stronger, and within the fragments is weaker, than previously supposed.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.