scholarly journals Towards a Practical, Non-enzymatic Process for Molnupiravir from Cytidine

Author(s):  
Vijayagopal Gopalsamuthiram ◽  
Appasaheb L. Kadam ◽  
Jeffrey Noble ◽  
David Snead ◽  
Corshai Williams ◽  
...  

A scalable four step synthesis of molnupiravir from cytidine is described herein. The attractiveness of this approach is its fully chemical nature involving inexpensive reagents and more environmentally friendly solvents such as water, isopropanol, acetonitrile and acetone. Isolation and purification procedures are improved in comparison to our earlier report, as all intermediates can be isolated via aqueous acid treatment and recrystallization. The key steps in the synthesis, namely ester formation, hydroxamination and deprotection were done on multigram scale to afford molnupiravir in 36-41% yield with average purity of 98 wt% by q-NMR and 99 area % by HPLC

2021 ◽  
Author(s):  
Vijayagopal Gopalsamuthiram ◽  
Appasaheb L. Kadam ◽  
Jeffrey Noble ◽  
David Snead ◽  
Corshai Williams ◽  
...  

A scalable four step synthesis of molnupiravir from cytidine is described herein. The attractiveness of this approach is its fully chemical nature involving inexpensive reagents and more environmentally friendly solvents such as water, isopropanol, acetonitrile and acetone. Isolation and purification procedures are improved in comparison to our earlier report, as all intermediates can be isolated via aqueous acid treatment and recrystallization. The key steps in the synthesis, namely ester formation, hydroxamination and deprotection were done on multigram scale to afford molnupiravir in 36-41% yield with average purity of 98 wt% by q-NMR and 99 area % by HPLC


1988 ◽  
Vol 66 (7) ◽  
pp. 1609-1616 ◽  
Author(s):  
LÊ H. Dao ◽  
Gérard Perrier ◽  
Kenneth Cole

A new polymorph of hydroxyaluminum phthalocyanine (PcAlOH) was obtained when PcAlOH thin film was exposed to aqueous acid solutions. The new polymorph, which is characterized by infrared, near-infrared, and visible absorption spectrometry and X-ray diffractometry, shows enhanced photoactivity in a photoelectrochemical solar cell device.


1946 ◽  
Vol 83 (2) ◽  
pp. 97-104 ◽  
Author(s):  
Maclyn McCarty ◽  
Oswald T. Avery

1. An improved method is outlined for the isolation and purification of the pneumococcal transforming substance. This method makes use of the fact that citrate inhibits the destructive action of the enzyme, desoxyribonuclease, which is released together with the active material during lysis of the living bacterial cells. A fivefold greater yield of purified transforming agent is obtained by the present method than by the procedure previousiy described. 2. The specific transforming substance has been isolated from pneumococci of types II and VI, in addition to Type III. In each instance the biologically active material has been found to consist of desoxyribonucleic acid.


1944 ◽  
Vol 43 (5) ◽  
pp. 330-336 ◽  
Author(s):  
H. B. Day

The experiments here described proved that preparations made from widely different classes of bacteria are capable of inducing immunity in mice against pneumococci. The success of these preparations was found to depend on the differential separation of an active immunizing antigen from another bacterial constituent—an ‘opposition factor’—which interferes with immunization. Further investigation and comparison depend largely on the discovery of a really effective method for the isolation and purification of the active antigen. Until its chemical nature is determined, the identity of the pneumococcal species antigen with similarly acting substances found in other bacteria remains unproved.Pathogenic bacteria depend for their virulence and invasiveness on certain products individual to the species or type, and specific immunity is due to the development of the appropriate antibodies. But chemotherapy, as in the case of the sulphonamides, interferes with a less specialized metabolic process of the microbes and is neither species nor type specific in action. It is reasonable to infer that bacteria may possess in common a vital process associated with the presence of a common constituent which may be antigenic. ‘Species antigen’ may be a substance of this nature.In view of the wide distribution of ‘species antigen’ among bacteria generally, it is probable that this constituent has already been separated and named in accordance with its presence in a particular species, but irrespective of its potential immunizing capacity.So far as pneumococci are concerned, there is good evidence that species antigen may be identical with the species C carbohydrate. Tillett (1927) found that rabbits injected with successive courses of heat-killed pneumococci, whether of types I, II, III or of avirulent rough strains, developed an equal increase of resistance to infection by type III Pneumococcus. In 1936 Enders, Wu & Shaffer varied the procedure, and by injections of rough pneumococci prepared an antiserum which gave passive protection to rabbits against infection by type III Pneumococcus. This antiserum lost its protective power after absorption with the species C carbohydrate.


1932 ◽  
Vol 56 (3) ◽  
pp. 307-317 ◽  
Author(s):  
Albert B. Sabin

Methods employed by Willstätter and his coworkers in the isolation and purification of enzymes have been applied to the virus of poliomyelitis. Rhoads (6) showed that alumina gel C mixed with poliomyelitis virus in certain proportions at an acid pH resulted in the adsorption and inactivation of the virus. The experiments in this communication confirm Rhoads' observation, and show further that the adsorption as well as the inactivation are reversible; i.e., by changing the pH to the alkaline side with M/15 Na2HPO4 it is possible to free the virus in a state in which it is again capable of producing typical poliomyelitis. These experiments show also that by this process the virus undergoes considerable purification by diminution in the concentration of non-virus-containing substances. Washing the alumina gel C-virus complex with M/5 NaCl-M/15 KH2PO4 apparently dissociates no virus but is capable of freeing a certain amount of extractible organic substances. Furthermore, it is possible to increase the degree of purity and concentration of the virus by distillation in vacuo, and subsequent repeated adsorptions and elutions. By such partial purification and concentration, a virus solution with a minimal effective dose (as regards the production of typical poliomyelitis) of 0.0003 cc. was obtained. This solution had 0.04 mg. N per cc., and gave negative biuret, xanthoproteic, and ninhydrin reactions. These methods offer an opportunity for the preparation of a quantity of sufficiently purified and concentrated poliomyelitis virus to warrant the beginning of a study of its chemical nature; they also offer a means of anchoring the virus to an insoluble, and centrifugable substance (alumina gel C), which promises to facilitate various immunological studies, that might otherwise have been impossible.


1992 ◽  
Vol 282 ◽  
Author(s):  
V. A. Burrows ◽  
V. S. G. Kondapuram

ABSTRACTThe interaction of semiconductor surfaces with aqueous acid solutions is important in chemical cleaning and etching. Wet chemical treatments are advantageous because they cause little damage to the surface and do not usually require high temperatures. The surface chemistry of GaAs after treatment with phosphoric acid was studied using multiple internal reflection infrared spectroscopy. The treatment left behind a thin film containing several types of PxOy bonds. The chemical nature of the film was observed to change with time as new species would form on the surface.


Synthesis ◽  
2019 ◽  
Vol 51 (17) ◽  
pp. 3295-3304
Author(s):  
Alexander Lehr ◽  
Andrea Frank ◽  
Winfried Münch ◽  
Ulrich Dietz ◽  
Udo Nubbemeyer

Extensive investigation of nitrated phospholipids in connection with various biologically important processes requires reliable access to suitable material. A selective chemical synthesis introducing a defined nitrofatty acid at the sn-2 position of a 2-lyso sn-glycero-3-phosphatidylcholine was developed. Given that the nitroalkene moiety of both reactant nitrofatty acid derivative and the product esters is characterised by particular sensitivity to nucleophile addition and, depending on the intermediate, subsequent olefin isomerisation and retro-Henry-type reaction, a reliable two-step ester formation was introduced. The activation of the nitrofatty acid succeeded after reaction with trichlorobenzoyl chloride, and the mixed anhydride could be isolated via extractive work-up. Subsequent reaction with 1-palmitoyl-2-lyso-sn-glycero-3-phosphatidylcholine enabled the sn-2 esterification to be achieved with high yield by using a minimum of reagents, avoiding the formation of side products and facilitating final isolation and purification.


Author(s):  
George F. Leeper

Polysaccharide elementary fibrils are usually fasciated into microfibrils of from one hundred to a few hundred Angstroms wide. Cellulose microfibrils when subjected to acid treatment dissociate into component elementary fibrils. For pectic acid it was observed that variations in pH could cause a change in the fasciation of the elementary fibrils.Solutions of purified pectic acid and sodium phosphotungtate were adjusted to various pH levels with NaOH or HCl and diluted to give a final concentration of 0.5 and 1% for the polysaccharide and negative stains respectively. Micrographs were made of the samples after drying on a carbon film covered grid. The average number of elementary fibrils was determined by counting the number of elementary fibrils in each fascicle intersected by lines drawn across the micrograph.


Author(s):  
Richard R. Shivers

The sinus gland is a neurohemal organ located in the crayfish eyestalk and represents a storage site for neurohormones prior to their release into the circulation. The sinus gland contains 3 classes of dense, membrane-limited granules: 1) granules measuring less than 1000 Å in diameter, 2) granules measuring 1100-1400 Å in diameter, and 3) granules measuring 1500-2000 Å in diameter. Class 3 granules are the most electron-dense of the granules found in the sinus gland, while class 2 granules are the most abundant. Generally, all granules appear to undergo similar changes during release.Release of neurosecretory granules may be initiated by a preliminary fragmentation of the “parent granule” into smaller, less dense vesicles which measure about 350 Å in diameter (V, Figs. 1-3). A decrease in density of the granules prior to their fragmentation has been observed and may reflect a change in the chemical nature of the granule contents.


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