A Concise Flow Synthesis of Efavirenz

Correia, Camille A.; Gilmore, Kerry; McQuade, D. Tyler; Seeberger, Peter H.

doi:10.1002/anie.201411728

Cited by 107 publications

(47 citation statements)

References 28 publications

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“…Numerous APIs [5] including artemisinin, [5h] rufinamide [6] and efavirenz [7] have been elegantly synthesized in multi-step continuous-flow systems. Though relatively unexplored, [8] multi-step biosynthesis could provide two major benefits to continuous-flow syntheses.…”

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confidence: 99%

Ten‐Minute Protein Purification and Surface Tethering for Continuous‐Flow Biocatalysis

et al. 2017

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Nature applies enzymatic assembly lines to synthesize bioactive compounds. Inspired by such capabilities, we have developed a facile method for spatially segregating attached enzymes in a continuous-flow, vortex fluidic device (VFD). Fused Hisn-tags at the protein termini allow rapid bioconjugation and consequent purification through complexation with immobilized metal affinity chromatography (IMAC) resin. Six proteins were purified from complex cell lysates to average homogeneities of 76%. The most challenging to purify, tobacco epi-aristolochene synthase, was purified in only ten minutes from cell lysate to near homogeneity (>90%). Furthermore, this “reaction-ready” system demonstrated excellent stability during five days of continuous-flow. Towards multi-step transformations in continuous flow, proteins were arrayed as ordered zones on the reactor surface allowing segregation of catalysts. Ordering enzymes into zones opens new opportunities for continuous flow biosynthesis.

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confidence: 99%

Ten‐Minute Protein Purification and Surface Tethering for Continuous‐Flow Biocatalysis

et al. 2017

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“…For the cases where outputs are low and the reactor is to be operated as and when demand arises, every start-up time and shut-down time play a critical role in deciding the effective profit from that operation. This issue can be very important in case of pharmaceuticals and nanomaterials where production capacities are low and material costs are very high [25][26][27][28][29][30][31].…”

Section: Evaluating the Role Of Process Equipment In Steady Operationmentioning

confidence: 99%

Exploring the Steady Operation of a Continuous Pilot Plant for the Di‐Nitration Reaction

2019

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Continuous‐flow synthesis of the selective herbicide pendimethalin was demonstrated in both a laboratory‐scale and a pilot‐scale reactor using only concentrated nitric acid as nitrating agent. The di‐nitration reaction follows second‐order kinetics where the reaction is first order with respect to both reactant and nitric acid. The pinched‐tube reactor was chosen for pilot‐scale reactor fabrication due to its excellent mixing and mass transfer characteristics compared to a straight‐tube reactor. The estimated mass transfer coefficient showed similar nature in the laboratory‐scale and the pilot‐scale pinched‐tube reactor, ensuring similar performance at the pilot scale. Di‐nitration in continuous flow, inline quenching, extraction, and phase separation are some of the salient features of the developed pilot plant. The importance of the start‐up time for achieving steady state in the flow system at the large scale is highlighted.

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“…convertedi nto efavirenz in as ingle operation by using af low system. [19] Following catalyst optimization, catalyst 10,w hich contained a4-cyanophenyl group, afforded compound 14 with 91 % ee.…”

Section: Addition Of the Cf 3 Nucleophile To Ynonesmentioning

confidence: 99%

Catalytic Asymmetric Synthesis of α‐Trifluoromethylated Carbinols: A Case Study of Tertiary Propargylic Alcohols

2018

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Enantioenriched CF 3 -substituted tertiary alcohols have been applied in ab road range of chemical disciplines, including medicinal chemistry and agrochemistry. The widely prescribed anti-HIV pharmaceutical efavirenz is one particular example of the application of these chiral building blocks. Because the typical synthetic route to this small drug molecule involves the stoichiometric use of ac hiral promoter,s ignificant effort has been devoted to the development of catalytic alternatives for accessing this building block.I n this Focus Review,w es ummarize the catalytic asymmetric synthesis of CF 3 -substituted tertiary propargylic alcohols based on three retrosynthetic approaches, namely one trifluoromethylation approacha nd two building-block strategies.T he general challenges that are involved in the construction of aC F 3 -substituted tetrasubstituted stereogenic carbon speciesa re highlighted and possible future directions in the field are discussed.

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A Concise Flow Synthesis of Efavirenz

Cited by 107 publications

References 28 publications

Ten‐Minute Protein Purification and Surface Tethering for Continuous‐Flow Biocatalysis

Ten‐Minute Protein Purification and Surface Tethering for Continuous‐Flow Biocatalysis

Exploring the Steady Operation of a Continuous Pilot Plant for the Di‐Nitration Reaction

Catalytic Asymmetric Synthesis of α‐Trifluoromethylated Carbinols: A Case Study of Tertiary Propargylic Alcohols

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