Synthesis of MeBmt and related derivatives <i>via</i> syn-selective ATH-DKR

Rolt, Adam; Liang, T Jake; Stachulski, Andrew V.

doi:10.1039/c9ra08256e

Cited by 11 publications

(4 citation statements)

References 32 publications

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“…Asymmetric transformations comprising DKR processes are very attractive since racemic substrates converge ideally to a diastereo- and enantiomerically pure product in this transformation. − In particular, the DKR encountered in asymmetric transfer hydrogenation (ATH) of ketones is a powerful protocol for “deracemization” of substrates, which possess a stereolabile α-carbon by converting them into alcohols with two contiguous stereogenic centers. − In 1989, Noyori and co-workers reported trailblazing work on the asymmetric hydrogenation of β-keto esters using Ru–BINAP catalysts . Since then, the utility of reductive DKR processes has been further accentuated by taking advantage of asymmetric transfer hydrogenation (ATH) with bifunctional Ru, Rh, and Ir catalysts containing chiral N -sulfonyl-1,2-diamine scaffolds. − …”

mentioning

confidence: 99%

Asymmetric Transfer Hydrogenation of α-Substituted-β-Keto Carbonitriles via Dynamic Kinetic Resolution

Wang

Yang

et al. 2021

J. Am. Chem. Soc.

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A catalytic protocol for the enantio-and diastereoselective reduction of α-substituted-β-keto carbonitriles is described. The reaction involves a DKR-ATH process with the simultaneous construction of β-hydroxy carbonitrile scaffolds with two contiguous stereogenic centers. A wide range of α-substituted-β-keto carbonitriles were obtained in high yields (94%−98%) and excellent enantio-and diastereoselectivities (up to >99% ee, up to >99:1 dr). The origin of the diastereoselectivity was also rationalized by DFT calculations. Furthermore, this methodology offers rapid access to the pharmaceutical intermediates of Ipenoxazone and Tapentadol.

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confidence: 99%

Asymmetric Transfer Hydrogenation of α-Substituted-β-Keto Carbonitriles via Dynamic Kinetic Resolution

Wang

Yang

et al. 2021

J. Am. Chem. Soc.

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“…In 2019, Stachulski and co-workers accomplished the ATH of -keto anilides catalyzed by the Ru-tethered complex (R,R)-CAT14 at 20 °C for 40 h with HCO 2 Na as the hydrogen donor and TBAI in H 2 O/CH 2 Cl 2 mixture (Scheme 48). 61 Under these reaction conditions, the reaction led to the syn-products in 48-75% yield, diastereoselectivities up to >95:5 (syn/anti) dr, and 26-98% ee. This method allowed the scope of the ATH/DKR leading to relevant -alkyl--hydroxy-N-Me-amino acids to be expanded.…”

Section: Scheme 47mentioning

confidence: 93%

Recent Progress and Applications of Transition-Metal-Catalyzed Asymmetric Hydrogenation and Transfer Hydrogenation of Ketones and Imines through Dynamic Kinetic Resolution

et al. 2020

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Based on the ever-increasing demand for enantiomerically pure compounds, the development of efficient, atom-economical, and sustainable methods to produce chiral alcohols and amines is a major concern. Homogeneous asymmetric catalysis with transition-metal complexes including asymmetric hydrogenation (AH) and transfer hydrogenation (ATH) of ketones and imines through dynamic kinetic resolution (DKR) allowing the construction of up to three stereogenic centers is the main focus of the present short review, emphasizing the development of new catalytic systems combined to new classes of substrates and their applications as well.1 Introduction2 Asymmetric Hydrogenation via Dynamic Kinetic Resolution2.1 α-Substituted Ketones2.2 α-Substituted β-Keto Esters and Amides2.3 α-Substituted Esters2.4 Imine Derivatives3 Asymmetric Transfer Hydrogenation via Dynamic Kinetic Resolution3.1 α-Substituted Ketones3.2 α-Substituted β-Keto Esters, Amides, and Sulfonamides3.3 α,β-Disubstituted Cyclic Ketones3.4 β-Substituted Ketones3.5 Imine Derivatives4. Conclusion

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“…In addition, Bmt is difficult to isolate and purify from complex products. Some researchers have been working to obtain MeBmt through a chemical synthesis approach (Rolt et al, 2019). However, this method involves many steps, many intermediate products, and a low final yield, and is difficult to put into industrial production.…”

Section: Functional Analysis For the Highly Expressed Deps In The Frumentioning

confidence: 99%

Comparative proteomics reveals the mechanism of cyclosporine production and mycelial growth in Tolypocladium inflatum affected by different carbon sources

Wang,

Liu,

Mao

et al. 2023

Front. Microbiol.

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Cyclosporine A (CsA) is a secondary cyclopeptide metabolite produced by Tolypocladium inflatum that is widely used clinically as an immunosuppressant. CsA production and mycelial growth differed when T. inflatum was cultured in different carbon source media. During early fermentation, CsA was preferred to be produced in fructose medium, while the mycelium preferred to accumulate in sucrose medium. On the sixth day, the difference was most pronounced. In this study, high-throughput comparative proteomics methods were applied to analyze differences in protein expression of mycelial samples on day 6, revealing the proteins and mechanisms that positively regulate CsA production related to carbon metabolism. The differences included small molecule acid metabolism, lipid metabolism, organic catabolism, exocrine secretion, CsA substrate Bmt synthesis, and transcriptional regulation processes. The proteins involved in the regulation of mycelial growth related to carbon metabolism were also revealed and were associated with waste reoxidation processes or coenzyme metabolism, small molecule synthesis or metabolism, the stress response, genetic information or epigenetic changes, cell component assembly, cell wall integrity, membrane metabolism, vesicle transport, intramembrane localization, and the regulation of filamentous growth. This study provides a reliable reference for CsA production from high-efficiency fermentation. This study provides key information for obtaining more CsA high-yielding strains through metabolic engineering strategies.

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Synthesis of MeBmt and related derivatives via syn-selective ATH-DKR

Abstract: The unusual α-amino, β-hydroxy acid MeBmt is a key structural feature of cyclosporin A, an important naturally occurring immunosuppressant and antiviral agent. We describe a concise synthesis of MeBmt using the principle of dynamic kinetic resolution.

Cited by 11 publications

References 32 publications

Asymmetric Transfer Hydrogenation of α-Substituted-β-Keto Carbonitriles via Dynamic Kinetic Resolution

Asymmetric Transfer Hydrogenation of α-Substituted-β-Keto Carbonitriles via Dynamic Kinetic Resolution

Recent Progress and Applications of Transition-Metal-Catalyzed Asymmetric Hydrogenation and Transfer Hydrogenation of Ketones and Imines through Dynamic Kinetic Resolution

Comparative proteomics reveals the mechanism of cyclosporine production and mycelial growth in Tolypocladium inflatum affected by different carbon sources

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