TMC-95A–D and analogues: Chemistry and biology

Coste, Alexis; Couty, François; Evano, Gwilherm

doi:10.1016/j.crci.2008.06.003

Cited by 11 publications

(7 citation statements)

References 40 publications

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“…The latter ones have exhibited efficient catalytic activity in the asymmetric Mannich reaction. In fact, the use of simple trans -(1 R, 2 R )-aminoindanol ( 1c ) as an efficient organocatalyst in the enantioselective synthesis of natural products as the TMC-954 core [ 12 – 13 ], has been recently reported. These examples show the high catalytic potential that this versatile motif exhibits [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

The aminoindanol core as a key scaffold in bifunctional organocatalysts

Sonsona¹,

Marqués‐López²,

Herrera³

2016

Beilstein J. Org. Chem.

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SummaryThe 1,2-aminoindanol scaffold has been found to be very efficient, enhancing the enantioselectivity when present in organocatalysts. This may be explained by its ability to induce a bifunctional activation of the substrates involved in the reaction. Thus, it is easy to find hydrogen-bonding organocatalysts ((thio)ureas, squaramides, quinolinium thioamide, etc.) in the literature containing this favored structural core. They have been successfully employed in reactions such as Friedel–Crafts alkylation, Michael addition, Diels–Alder and aza-Henry reactions. However, the 1,2-aminoindanol core incorporated into proline derivatives has been scarcely explored. Herein, the most representative and illustrative examples are compiled and this review will be mainly focused on the cases where the aminoindanol moiety confers bifunctionality to the organocatalysts.

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Section: Introductionmentioning

confidence: 99%

The aminoindanol core as a key scaffold in bifunctional organocatalysts

Sonsona¹,

Marqués‐López²,

Herrera³

2016

Beilstein J. Org. Chem.

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“…Isatins are carbonyl-containing entities that can be converted to enantiomerically enriched 3-hydroxy-2-oxindoles found within alkaloids of substantial biological consequence xix . Examples are proteasome inhibitors TMC-95A–D with ample potential in the treatment of cancer and immune disorders xx , and interleukin 6 inhibitor and anti-osteoporosis agent madindoline A (Fig. 1a); proper configuration of the tertiary hydroxyl unit is needed for high activity xxi .…”

mentioning

confidence: 99%

Simple organic molecules as catalysts for enantioselective synthesis of amines and alcohols

Silverio

Torker

Pilyugina

et al. 2013

Nature

201

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The discovery of new catalysts that can generate complex organic compounds via enantioselective transformations is central to advances in the life sciences;i for this reason, many chemists try to discover catalysts that can be used to produce chiral molecules with a strong preference for one mirror image isomer.ii The ideal catalyst should be devoid of precious elementsiii and should bring reactions to completion in a few hours using operationally simple procedures. In this manuscript, we introduce a set of small organic molecules that can catalyze reactions of unsaturated organoboron reagents with imines and carbonyls; the products of the reactions are enantiomerically pure amines and alcohols, which can be used to synthesize more complex, biologically active molecules. A distinguishing feature of this new catalyst class is the presence of a 'key' proton embedded within their structure. The catalyst is derived from the abundant amino acid valine and was prepared in large quantities in four steps using inexpensive reagents. Reactions are scalable, do not demand stringent conditions, and can be performed with as little as 0.25 mol % catalyst in less than six hours at room temperature to generate products in >85% yield and ≥97:3 enantiomeric ratio. The efficiency, selectivity and operational simplicity of the transformations and the range of boron-based reagents render this advance vital to future progress in chemistry, biology and medicine.

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“…It seems as an optimized occupation of the substrate binding sites of the proteasome as well as the C-terminal group of these inhibitors play an important role for their observed potent inhibition [85]. The chemistry and biology of TMC-95s has been reviewed recently [86].…”

Section: Tmc-95smentioning

confidence: 99%

Macrocyclic Proteasome Inhibitors

Krahn¹,

Ottmann²,

Kaiser³

2011

CMC

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Proteasome inhibitors have proven to be effective anticancer agents. Despite the success of the first on the market proteasome inhibitor bortezomib in chemotherapy, alternative clinically useful proteasome inhibitors are still urgently needed as bortezomib therapy causes severe side effects and is limited by arising drug resistance. Experience from previous proteasome inhibitor studies has thereby demonstrated that the identification of proteasome inhibitor structures with suitable pharmacological properties is a key factor for a successful development of clinically useful proteasome inhibitors. Macrocycles often show distinct and in comparison to linear small molecules superior pharmacological properties. Consequently, macrocyclic proteasome inhibitors might represent promising small molecules for drug development. Here, we want to highlight the current state of the art of macrocyclic proteasome inhibitor research. To this end, we give an overview and critically discuss currently known classes of macrocyclic proteasome inhibitors.

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TMC-95A–D and analogues: Chemistry and biology

Cited by 11 publications

References 40 publications

The aminoindanol core as a key scaffold in bifunctional organocatalysts

The aminoindanol core as a key scaffold in bifunctional organocatalysts

Simple organic molecules as catalysts for enantioselective synthesis of amines and alcohols

Macrocyclic Proteasome Inhibitors

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