Review on Recent Developments in Biocatalysts for Friedel–Crafts Reactions

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(17), P. 10742 - 10763

Published: Aug. 17, 2022

The Friedel–Crafts (F–C) reaction has been a fundamental pillar of both academic and industrial synthetic organic chemistry since its discovery in 1873. Its success is based on the versatility applicability F–C reactions for wide range substrates, there have an impressive number publications patents describing catalytic methods. asymmetric version was discovered about 100 years after seminal work by Friedel Crafts become major area research. While chemical methods with much-improved efficacies scopes discovered, still suffer from limitations. Biocatalysis potential to be best solution this challenge because excellent selectivity (enantio-, chemo-, regioselectivity) displayed enzymes. In last two decades, advancements molecular biology techniques, bioinformatics, high-throughput screening, directed evolution, process scale-up led biocatalysis becoming mature field. It therefore not surprising that researchers around globe developed several biocatalysts reactions. Herein, we review recent developments design use stereoselective strategies performing

Language: Английский

---

Biocatalytic Friedel‐Crafts Reactions

ChemCatChem, Journal Year: 2022, Volume and Issue: 14(18)

Published: July 11, 2022

Abstract Friedel‐Crafts alkylation and acylation reactions are important methodologies in synthetic industrial chemistry for the construction of aryl‐alkyl aryl‐acyl linkages that ubiquitous bioactive molecules. Nature also exploits these many biosynthetic processes. Much work has been done to expand application enzymes unnatural substrates through directed evolution. The promise such biocatalysts is their potential supersede inefficient toxic chemical approaches reactions, with mild operating conditions ‐ hallmark enzymes. Complementary created bio‐hybrid catalysts consisting anchored into biomolecular scaffolds, which display same desirable characteristics. In this Review, we summarise efforts, focussing on both mechanistic aspects considerations, concluding an overview frontiers field routes towards more efficient benign future humankind.

Language: Английский

---

Expanding the Cation Cage: Squalene-Hopene Cyclase-Mediated Enantioselective Semipinacol Rearrangement

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(3), P. 1946 - 1951

Published: Jan. 19, 2023

Squalene-hopene cyclases (SHCs) are the biocatalytic pendant to asymmetric Brønsted-acid catalysis and thus comprise enormous synthetic potential. Nevertheless, their substrate scope is currently limited terpenes. Herein, we present how tailor SHC's cation cage for an enantioselective semipinacol rearrangement of bicyclic allylic alcohols produce valuable oxa-carbon spirocyclic compounds. Exploiting subtle divergence SHC active sites combined with structure-guided semirational engineering, designed a biocatalyst high catalytic performance ∼4500 TTN excellent enantioselectivity 99.5% enantiomeric excess (ee). In silico studies suggest that broadened site pivotal catalysis. This intricate cationic easily scalable, employing lyophilized cell powder in water. Furthermore, our demonstrate acceptance diverse ring-sized substrates but also reveal naturally confined limits function as general "semipinacolase." study showcases ability harness tap into broader field

Language: Английский

---

Prediction of the reaction mechanisms of sesquiterpene coumarin synthases supports a direct evolutionary link with triterpene biosynthesis

Phytochemistry Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Language: Английский

---

Alternative Active Site Confinement in Squalene–Hopene Cyclase Enforces Substrate Preorganization for Cyclization

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(7), P. 5073 - 5083

Published: March 29, 2023

Confinement of an enzyme's active site is critical to the efficiency chemical reactions and has been recognized as important tool for catalysis accelerate by proximity via specific interactions with substrate control course reaction. Despite these benefits, a strongly confined inherently limited compounds that resemble native substrate, only small deviations tolerated. To unlock potential modifying terpene scaffold building blocks interest branched isoprene/terpene motifs, present study demonstrates simple structure-guided strategy create alternative confinement in squalene–hopene cyclase from Alicyclobacillus acidocaldarius (AacSHC). This aims shape complementarity between protein enforce preorganization geranyl acetone analogs deviant isoprene patterns. Screening AacSHC variants affecting tunnel allowed us detect starting activity G600M variant. Structural analysis led identification reduced radii resulted steric decrease average distances double bond substrate's terminal unit catalytic site. Iterative saturation mutagenesis SHC screening analog dihydropseudoirone were used generate demonstrated further evolvability. The final variant showed 1174-fold increase total turnover number 111-fold increased compared wild-type. approach great overcome limitations engineering biocatalysts generation interesting blocks.

Language: Английский

---

Biocatalytic stereocontrolled head-to-tail cyclizations of unbiased terpenes as a tool in chemoenzymatic synthesis

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 10, 2024

Language: Английский

---

Recent advances in enzymatic carbon–carbon bond formation

RSC Advances, Journal Year: 2024, Volume and Issue: 14(36), P. 25932 - 25974

Published: Jan. 1, 2024

Enzymatic carbon-carbon (C-C) bond formation reactions have become an effective and invaluable tool for designing new biological medicinal molecules, often with asymmetric features. This review provides a systematic overview of key C-C enzymes, the focus reaction mechanisms recent advances. These include aldol reaction, Henry Knoevenagel condensation, Michael addition, Friedel-Crafts alkylation acylation, Mannich Morita-Baylis-Hillman (MBH) Diels-Alder acyloin condensations

Language: Английский

---

Chemoenzymatic synthesis of (+)-isoagatholactone, (+)-spongian-16-one, and 3-deoxychavalone A via biocatalytic polyene cyclization

Organic & Biomolecular Chemistry, Journal Year: 2023, Volume and Issue: 21(27), P. 5527 - 5531

Published: Jan. 1, 2023

The stereoselective cyclization of geranylgeraniol catalysed by squalene-hopene cyclase (SHC) was investigated. By use this transformation, spongiane diterpenoids (+)-isoagatholactone and (+)-spongian-16-one, meroterpenoid 3-deoxychavalone A were synthesized in a concise redox-economic manner. This work showcases the application SHC-catalysed as key step terpenoid synthesis.

Language: Английский

---

Squalene hopene cyclases and oxido squalene cyclases: potential targets for regulating cyclisation reactions

Biotechnology Letters, Journal Year: 2023, Volume and Issue: 45(5-6), P. 573 - 588

Published: April 14, 2023

Language: Английский

---

A Career in Catalysis: Bernhard Hauer

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(13), P. 8861 - 8889

Published: June 20, 2023

On the occasion of Professor Bernhard Hauer′s (partial) retirement, we reflect on and highlight his distinguished career in biocatalysis. Bernhard, a biologist by training, has greatly influenced biocatalysis with vision ideas throughout four-decade career. The development went hand evolution application enzymes for chemical processes. In this Account, present selected examples early work their an industrial setting, focus specific contributions to harnessing catalytic power novel reactions understanding engineering flexible loops channels catalysis.

Language: Английский

---