Catalytic Asymmetric Mannich Reaction with N‐Carbamoyl Imine Surrogates of Formaldehyde and Glyoxylate

You, Yang’en; Zhang, Long; Cui, Linfeng; Mi, Xueling; Luo, Sanzhong

doi:10.1002/ange.201707005

Cited by 15 publications

(5 citation statements)

References 55 publications

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“…The resulting β-amino carbonyl compounds are versatile synthetic building blocks for a wide variety of natural products and biologically active compounds 9 . Different types of formaldehyde-derived imines or iminium salts, which are generally unstable and have to be in situ generated from formaldehyde with aromatic amines 10,11 , α-aminomethyl ethers [12][13][14][15][16][17] , N,O-acetals [18][19][20] , or 1,3,5-triaryl-1,3,5-triazines [21][22][23][24] , have been successfully applied. Within this context, enantioselective version of this transformation has also been achieved by catalytic asymmetric activation of the nucleophilic carbonyl compounds with either amine catalysts 10,11,14,16 or chiral Lewis acid 23,24 .…”

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confidence: 99%

Enantioselective three-component aminomethylation of α-diazo ketones with alcohols and 1,3,5-triazines

et al. 2020

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Enantioselective α-aminomethylation of carbonyl compounds constitutes a powerful protocol for introducing aminomethyl groups to simple organic molecules. However, current strategies rely on nucleophile-based enantioselective activation with inherently activated substrates only, and enantioselective protocol based on the activation of in situ-generated unstable formaldimines remains elusive, probably owing to their unstable nature and the lack of steric environment for efficient stereocontrols. Here, based on a rhodium/chiral phosphoric acid cooperative catalysis, we achieved an enantioselective three-component reaction of α-diazo ketones with alcohols and 1,3,5-triazines. A dual hydrogen bonding between the chiral phosphoric acid catalyst and two distinct active intermediates was proposed to be crucial for the efficient electrophile-based enantiocontrol. A series of chiral β-amino-α-hydroxy ketones including those derived from simple aliphatic alcohols, allylic alcohol, propargyl alcohol, complicated natural alcohols and water could all be prepared in high efficiency and enantioselectivity.

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confidence: 99%

Enantioselective three-component aminomethylation of α-diazo ketones with alcohols and 1,3,5-triazines

et al. 2020

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“…Thereafter, it underwent aminolysis with NH 4 Cl under basic conditions to give intermediate 6 . Subsequently, intermediate 6 underwent condensation with paraformaldehyde, followed by the acylation reaction with acetic anhydride to obtain intermediate 7 . A coupling reaction between intermediate 7 and tofacitinib provided intermediate 8 , and the target compound 9 was afforded by the deprotection of intermediate 8 (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

Discovery of a Colon-Targeted Azo Prodrug of Tofacitinib through the Establishment of Colon-Specific Delivery Systems Constructed by 5-ASA–PABA–MAC and 5-ASA–PABA–Diamine for the Treatment of Ulcerative Colitis

et al. 2022

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To mitigate the systemic adverse effects of tofacitinib, 5-ASA–PABA–MAC and 5-ASA–PABA–diamine colon-specific delivery systems were constructed, and tofacitinib azo prodrugs 9 and 20a–20g were synthesized accordingly. The release studies suggested that these systems could effectively release tofacitinib in vitro, and the 5-ASA–PABA–diamine system could successfully realize the colon targeting of tofacitinib in vivo. Specifically, compound 20g displayed a 3.67-fold decrease of plasma AUC(tofacitinib, 0–∞) and a 9.61-fold increase of colonic AUC(tofacitinib, 0–12h), compared with tofacitinib at a molar equivalent oral dose. Moreover, mouse models suggested that compound 20g (1.5 mg/kg) could achieve roughly the same efficacy against ulcerative colitis compared with tofacitinib (10 mg/kg) and did not impair natural killer cells. These results demonstrated the feasibility of compound 20g as an effective alternative to mitigate the systemic adverse effects of tofacitinib, and 5-ASA–PABA–MAC and 5-ASA–PABA–diamine systems were proven to be effective for colon-specific drug delivery.

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“…In 2017, we developed an asymmetric Mannich reaction with N , O ‐acetals as imine surrogates, furnishing α ‐ or β ‐amino carbonyls with high enantioselectivity. [ 42 ] The method was also amenable to other acetaldimine precursors to introduce functional groups such as CF 3 ‐ or CF 2 H‐ group. [ 43 ] On the blueprint of retro‐Claisenase in nature, [ 44‐45 ] we developed the first asymmetric retro‐Claisen…”

Section: Bi/multi‐function Strategy: Development and Application Of C...mentioning

confidence: 99%

Bio‐inspired Small Molecular Catalysis

2022

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Comprehensive Summary Nature is an inspiring resource for chemists to exploit uncharted chemical spaces. Enzymes in nature are characteristic of high efficiency and exquisite stereocontrol under rather mild conditions. Not surprisingly, chemists have a long history in developing new catalysts by learning from and imitating the natural enzymes. This review summarizes our long‐standing efforts in developing bio‐inspired small molecular catalysis. These were categorized according to the employed strategies: 1) bi‐/multi‐functional strategy for the bio‐inspired chiral primary amine catalyst; 2) cofactor strategy for bio‐inspired ortho‐quinone catalyst; 3) intermediate strategy for chiral latent carbocation catalysis based on natural carbocation process. Each section includes brief introduction of the biological origin, design of catalyst, development of methodology as well as the underlying mechanistic insights. What is the most favorite and original chemistry developed in your research group? I hope it's always the next one. How do you get into this specific field? Could you please share some experiences with our readers? Nature provides many astonishing catalytic machineries for building up molecular complexity and harnessing energy in the most efficient ways. Nature's recipe for catalysis serves as a starting point to develop new catalyst for synthetic and energy chemistry. I was trained as a synthetic chemist in a physical organic group in Nankai and ICCAS, and spent part of my graduate studies doing enzymatic synthesis of oligosaccharide and its related biological applications in Ohio State University. This gave me a mixed view on organocatalysis, then under its golden stage of renaissance, not only for its synthetic potentials as a new catalytic concept, but also with an eye on its biological origin and possible impact beyond synthesis. I also benefit a lot from the physical organic chemistry training which helps to shape my research path in width and depth, in a way I never imagined and expected at the beginning of my career. How do you supervise your students? Try to inspire beyond instruct. I learned and am still learning. “因材施教” is easy to say than to do. In reality, I become bossy the way I dislike and have to instruct heavily. What is the most important personality for scientific research? Curiosity, broad reading and sufficient “free time” for daydreaming. In order to have enough time to waste, you have to work really hard at first. Who influences you mostly in your life? My Ph.D. supervisor, Prof. Jin‐Pei Cheng who teaches me a rational and quantitative view for chemistry and inspires me all the time to pursue a rational approach in research.

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Catalytic Asymmetric Mannich Reaction with N‐Carbamoyl Imine Surrogates of Formaldehyde and Glyoxylate

Cited by 15 publications

References 55 publications

Enantioselective three-component aminomethylation of α-diazo ketones with alcohols and 1,3,5-triazines

Enantioselective three-component aminomethylation of α-diazo ketones with alcohols and 1,3,5-triazines

Discovery of a Colon-Targeted Azo Prodrug of Tofacitinib through the Establishment of Colon-Specific Delivery Systems Constructed by 5-ASA–PABA–MAC and 5-ASA–PABA–Diamine for the Treatment of Ulcerative Colitis

Bio‐inspired Small Molecular Catalysis

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