scholarly journals Safe and highly efficient adaptation of potentially explosive azide chemistry involved in the synthesis of Tamiflu using continuous-flow technology

2019 ◽  
Vol 15 ◽  
pp. 2577-2589 ◽  
Author(s):  
Cloudius R Sagandira ◽  
Paul Watts
Keyword(s):  
Continuous Flow ◽  
Shikimic Acid ◽  
Scale Up ◽  
Highly Efficient ◽  
Synthetic Routes

Tamiflu is one of the most effective anti-influenza drugs, which is currently manufactured by Hoffmann-La Roche from shikimic acid. Owing to its importance, more than 60 synthetic routes have been developed to date, however, most of the synthetic routes utilise the potentially hazardous azide chemistry making them not green, thus not amenable to easy scale up. Consequently, this study exclusively demonstrated safe and efficient handling of potentially explosive azide chemistry involved in a proposed Tamiflu route by taking advantage of the continuous-flow technology. The azide intermediates were safely synthesised in full conversions and >89% isolated yields.

scholarly journals Safe and highly efficient adaptation of potentially explosive azide chemistry involved in the synthesis of Tamiflu using continuous flow technology

2019 ◽  
Author(s):  
Cloudius Sagandira ◽  
Paul Watts
Keyword(s):  
Continuous Flow ◽  
Shikimic Acid ◽  
Scale Up ◽  
Highly Efficient ◽  
Synthetic Routes

Tamiflu is one of the most effective anti-influenza drugs, which is currently manufactured by Hoffmann-La Roche from shikimic acid. Owing to its importance, more than 60 synthetic routes have been developed to date, however most of the synthetic routes utilise the potentially hazardous azide chemistry making them not green, thus not amenable to easy scale up. Consequently, this study exclusively demonstrated safe and efficient handling of potentially explosive azide chemistry involved in a proposed Tamiflu route by taking advantage of the continuous flow technology. The azide intermediates were safely synthesised in full conversions and >89 % isolated yields.  

Design of a continuous flow immobilized-cell reactor for biosynthetical production of L-aspartic acid

1985 ◽  
Vol 50 (10) ◽  
pp. 2122-2133 ◽  
Author(s):  
Jindřich Zahradník ◽  
Marie Fialová ◽  
Jan Škoda ◽  
Helena Škodová
Keyword(s):  
Aspartic Acid ◽  
Continuous Flow ◽  
Immobilized Cells ◽  
Scale Up ◽  
Fixed Bed ◽  
Packed Bed ◽  
Fixed Bed Reactor ◽  
Experimental Program ◽  
Design Parameters ◽  
Immobilized Cell

An experimental study was carried out aimed at establishing a data base for an optimum design of a continuous flow fixed-bed reactor for biotransformation of ammonium fumarate to L-aspartic acid catalyzed by immobilized cells of the strain Escherichia alcalescens dispar group. The experimental program included studies of the effect of reactor geometry, catalytic particle size, and packed bed arrangement on reactor hydrodynamics and on the rate of substrate conversion. An expression for the effective reaction rate was derived including the effect of mass transfer and conditions of the safe conversion-data scale-up were defined. Suggestions for the design of a pilot plant reactor (100 t/year) were formulated and decisive design parameters of such reactor were estimated for several variants of problem formulation.

DEVELOPMENT OF A RAPID CONTINUOUS FLOW SALT LEACHING KIT FOR FABRICATION OF POLY(3-HYDROXYBUTYRIC ACID-CO-3-HYDROXYVALERATE) (PHBV) POROUS 3-D SCAFFOLD

2015 ◽  
Vol 75 (1) ◽  
Author(s):  
Syazwan Aizad ◽  
Badrul Hisham Yahaya ◽  
Saiful Irwan Zubairi
Keyword(s):  
Conventional Method ◽  
Continuous Flow ◽  
Tap Water ◽  
Chemical Properties ◽  
Porous Scaffolds ◽  
Time Saving ◽  
Salt Particle ◽  
Salt Leaching ◽  
Leaching Process ◽  
Highly Efficient

Polyhydroxyalkanoates (PHAs) that are synthesized from bacteria that are predominantly produced by microbial fermentation processes on organic waste, such as palm oil mill effluent (POME), olive oil and kitchen waste, contribute to a sustainable waste management. A great variety of materials from this family can be produced, however the application of PHAs in the production of scaffolds in tissue engineering has been mainly constrained to poly(hydroxybutyrate-co-valerate) (PHBV) due to its highly adjustable physico-chemical properties. One of the common methods in making the 3-D scaffolds is by performing solvent-casting particulate-leaching (SCPL) process, but this process requires a long period of soaking in water to extract the entire salt particle in the 3-D scaffolds. Therefore, the objective of this study is to develop a new method to the conventional method of salt leaching process via a highly efficient continuous flow leaching kit. The salt leaching process was carried out by (1) immersing the 3-D porous scaffolds in a fabricated static container containing tap water and (2) by allowing a pre-setting continuous flow rate of water. The concentration of sodium chloride (NaCl) was calculated periodically for both processes based on the salt standard calibration curve. The results showed that the exhaustive salt leaching of the conventional process occurred at 48 ± 5 hrs with the needs of changing the water twice a day. In contrast, the exhaustive salt leaching process via continuous flow leaching kit occurred at 40 ± 5 mins, 72 times faster than the conventional method (p<0.05). Therefore, the salt leaching process using continuous flow leaching kit can be considered a highly efficient and time saving procedure as compared to the conventional method.  

Highly Efficient Continuous Flow Reactions Using Singlet Oxygen as a “Green” Reagent

2011 ◽  
Vol 13 (19) ◽  
pp. 5008-5011 ◽  
Author(s):  
François Lévesque ◽  
Peter H. Seeberger
Keyword(s):  
Singlet Oxygen ◽  
Continuous Flow ◽  
Highly Efficient

scholarly journals Diels–Alder reactions of myrcene using intensified continuous-flow reactors

2017 ◽  
Vol 13 ◽  
pp. 120-126 ◽  
Author(s):  
Christian H Hornung ◽  
Miguel Á Álvarez-Diéguez ◽  
Thomas M Kohl ◽  
John Tsanaktsidis
Keyword(s):  
Continuous Flow ◽  
Flow Reactor ◽  
Scale Up ◽  
Reaction Times ◽  
Alder Reaction ◽  
Diels Alder ◽  
Flow Reactors ◽  
Diels Alder Reaction ◽  
Naturally Occurring ◽  
Continuous Flow Reactors

This work describes the Diels–Alder reaction of the naturally occurring substituted butadiene, myrcene, with a range of different naturally occurring and synthetic dienophiles. The synthesis of the Diels–Alder adduct from myrcene and acrylic acid, containing surfactant properties, was scaled-up in a plate-type continuous-flow reactor with a volume of 105 mL to a throughput of 2.79 kg of the final product per day. This continuous-flow approach provides a facile alternative scale-up route to conventional batch processing, and it helps to intensify the synthesis protocol by applying higher reaction temperatures and shorter reaction times.

scholarly journals Optimization and Scale-Up of the Continuous Flow Acetylation and Nitration of 4-Fluoro-2-methoxyaniline to Prepare a Key Building Block of Osimertinib

2020 ◽  
Vol 24 (10) ◽  
pp. 2217-2227
Author(s):  
Manuel Köckinger ◽  
Benjamin Wyler ◽  
Christof Aellig ◽  
Dominique M. Roberge ◽  
Christopher A. Hone ◽  
...  
Keyword(s):  
Building Block ◽  
Continuous Flow ◽  
Scale Up
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