Baker’s yeast catalyzed preparation of a new enantiomerically pure synthon of (S)-pramipexole and its enantiomer (dexpramipexole)

Ferraboschi, Patrizia; Ciceri, Samuele; Ciuffreda, Pierangela; Mieri, Maria De; Romano, Diego; Grisenti, Paride

doi:10.1016/j.tetasy.2014.07.011

Cited by 10 publications

(19 citation statements)

References 26 publications

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“…The stereoselective reduction of the achiral diketone 1 h provides the key chiral precursor for the synthesis of a number of hormonal contraceptives (i.e., desogestrel, norgestrel, gestodene) . The bio‐transformation of 1 h is complicated by the low solubility of the substrate in water; recently, we reported the use of different bio‐catalysts for the stereoselective mono‐reduction of 1 h and noticed that the use of EtOH (both to increase solubility and favour co‐factor regeneration) was beneficial for bio‐transformations with whole microbial cells . Thus, the reduction of 1 h with marine yeasts was performed in the presence of different amounts of EtOH (1–5 %), and the best results were found with an EtOH concentration of 3.5 %.…”

Section: Resultsmentioning

confidence: 99%

“…The reaction progress, ee and diastereomeric excess ( de ) were determined by using HPLC using a Lux Cellulose‐2 column ( n ‐hexane/ i PrOH 85:15; 0.5 mL min −1 254 nm); t r (13 S , 17 S )‐ 2 h 18.87 min, (13 S , 17 R )‐ 2 h 20.62 min, (13R, 17S)‐ 2 h 23.34 min, (13R, 17S)‐ 2 h , 24.61 min . White solid.…”

Section: Methodsmentioning

confidence: 99%

“…The reaction progress and ee were determined by using HPLC using a Chiralpak IA column ( n ‐hexane/ i PrOH 8:2 as eluent, flow rate: 0.7 mL min −1 , 254 nm), t r ( R )‐ 2 i 10.9 min, t r ( S )‐ 2 i 14.8 min . Yellowish solid.…”

Section: Methodsmentioning

confidence: 99%

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Seawater‐Based Biocatalytic Strategy: Stereoselective Reductions of Ketones with Marine Yeasts

et al. 2016

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The large consumption of freshwater in fermentations and bio‐transformations is a matter of concern for the sustainability of many bio‐processes. The use of seawater to perform bio‐processes is a sustainable alternative. In this work, we used marine yeasts from deep‐sub‐seafloor sediments grown in seawater as bio‐catalysts to perform the stereoselective reduction of different ketones, and the bio‐transformations were accomplished in seawater as well. Strains of Meyerozyma guilliermondii and Rhodotorula mucilaginosa were able to reduce different aromatic ketones with high molar conversions and moderate‐to‐high enantioselectivity with no significant differences between bio‐catalysis performed in seawater and freshwater. Finally, the selected marine yeasts were used for the reduction of key intermediates in seawater for the synthesis of molecules of pharmaceutical interest (desogestrel, norgestrel, gestodene, pramipexole).

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Seawater‐Based Biocatalytic Strategy: Stereoselective Reductions of Ketones with Marine Yeasts

et al. 2016

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“…Interestingly, Ferraboschi et al described the preparation of (–)-pramipexole and dexpramipexole using baker’s yeast based on the highly stereoselective transformation allowed by these biocatalysts ( Scheme 5 ) [ 81 ].…”

Section: Dexpramipexole For the Treatment Of Alsmentioning

confidence: 99%

From Riluzole to Dexpramipexole via Substituted-Benzothiazole Derivatives for Amyotrophic Lateral Sclerosis Disease Treatment: Case Studies

et al. 2020

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The 1,3-benzothiazole (BTZ) ring may offer a valid option for scaffold-hopping from indole derivatives. Several BTZs have clinically relevant roles, mainly as CNS medicines and diagnostic agents, with riluzole being one of the most famous examples. Riluzole is currently the only approved drug to treat amyotrophic lateral sclerosis (ALS) but its efficacy is marginal. Several clinical studies have demonstrated only limited improvements in survival, without benefits to motor function in patients with ALS. Despite significant clinical trial efforts to understand the genetic, epigenetic, and molecular pathways linked to ALS pathophysiology, therapeutic translation has remained disappointingly slow, probably due to the complexity and the heterogeneity of this disease. Many other drugs to tackle ALS have been tested for 20 years without any success. Dexpramipexole is a BTZ structural analog of riluzole and was a great hope for the treatment of ALS. In this review, as an interesting case study in the development of a new medicine to treat ALS, we present the strategy of the development of dexpramipexole, which was one of the most promising drugs against ALS.

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“…Among others, Pichia stipites CBS 6054 was found as one allowed obtaining chiral product with ee of 80%. The other products of yeast-mediated enantioselective bioreduction are chiral bicyclic alcohols, e.g., synthons of (S)pramipexole (anti-Parkinson drug) ( Figure 6) and also its (R) isomer-considered as an antiamyotrophic lateral sclerosis (ALS) agent [59]. Chirality is introduced into these molecules by the prochiral bicyclic ketone ( Figure 6) reduction mediated by Sachcaromyces cerevisiae, and this is the crucial step of the sequences of the reaction leading to the final enantiomers of pramipexole.…”

Section: Yeasts As Whole-cell Biocatalystsmentioning

confidence: 99%

Yeast as a Versatile Tool in Biotechnology

Żymańczyk–Duda¹,

Brzezińska-Rodak²,

MagdalenaKlimek-Ochab³

et al. 2017

Yeast - Industrial Applications

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Yeasts represent a very diverse group of microorganisms, and even strains that are classified as the same species often show a high level of genetic divergence. Yeasts biodiversity is closely related to their applicability. Biotechnological importance of yeast is almost immeasurable. For centuries, people have exploited its enzymatic potential to produce fermented food as bread or alcoholic beverages. Admittedly, yeasts application was initially instinctual, but with science and technology development, these microorganisms got the object of thorough scientific investigations. It must be recognized that yeast represents an excellent scientific model because of its eukaryotic origin and knowledge of genetics of yeast cells as well as metabolism examined in detail. In 1996, the genome of baker yeast Saccharomyces cerevisiae has been elucidated, what opened the opportunity for the global study of the expression and functioning of the eukaryotic genome. Also, currently, an international team is working on the synthesis of the 16 yeast chromosomes by synthetic biology tools, and the results are expected till the end of the year. Nowadays, yeast is regarded as a versatile tool for biotechnological purposes.

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Baker’s yeast catalyzed preparation of a new enantiomerically pure synthon of (S)-pramipexole and its enantiomer (dexpramipexole)

Cited by 10 publications

References 26 publications

Seawater‐Based Biocatalytic Strategy: Stereoselective Reductions of Ketones with Marine Yeasts

Seawater‐Based Biocatalytic Strategy: Stereoselective Reductions of Ketones with Marine Yeasts

From Riluzole to Dexpramipexole via Substituted-Benzothiazole Derivatives for Amyotrophic Lateral Sclerosis Disease Treatment: Case Studies

Yeast as a Versatile Tool in Biotechnology

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