- SUBSTITUTED STRAIGHT CHAIN SPIRO DERIVATIVES
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Provided herein are pharmaceutical agents useful for therapy and/or prophylaxis in a mammal, pharmaceutical composition comprising such compounds, and their use as menin/MLL protein/protein interaction inhibitors, useful for treating diseases such as cancer, including but not limited to leukemia, myelodysplastic syndrome (MDS), and myeloproliferative neoplasms (MPN); and diabetes.
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Page/Page column 107
(2021/06/26)
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- Photoenzymatic Synthesis of α-Tertiary Amines by Engineered Flavin-Dependent "ene"-Reductases
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α-Tertiary amines are a common motif in pharmaceutically important molecules but are challenging to prepare using asymmetric catalysis. Here, we demonstrate engineered flavin-dependent ‘ene'-reductases (EREDs) can catalyze radical additions into oximes to prepare this motif. Two different EREDs were evolved into competent catalysts for this transformation with high levels of stereoselectivity. Mechanistic studies indicate that the oxime contributes to the enzyme templated charge-transfer complex formed between the substrate and cofactor. These products can be further derivatized to prepare a variety of motifs, highlighting the versatility of ERED photoenzymatic catalysis for organic synthesis.
- Gao, Xin,Turek-Herman, Joshua R.,Choi, Young Joo,Cohen, Ryan D.,Hyster, Todd K.
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supporting information
p. 19643 - 19647
(2021/12/01)
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- Anionic cascade reactions. One-pot assembly of (Z)-chloro-exo- methylenetetrahydrofurans from β-hydroxyketones
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The assembly of (Z)-chloro-exo-methylenetetrahydrofurans by an original and connective anionic cascade sequence is reported. Base-catalysed condensation of β-hydroxyketones with 1,1-dichloroethylene generates, in moderate to good yields, the corresponding
- Marko, Istvan E.,Schevenels, Florian T.
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supporting information
p. 1319 - 1325
(2013/08/23)
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- Direct conversion of β-hydroxyketones to cyclic disiloxanes
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β-Hydroxyketones can be directly converted to cyclic disiloxanes using diphenylchlorosilane in the presence of imidazole and an amine base. The reaction is proposed to proceed via a nucleophilic activation mechanism through a cyclic chairlike transition state affording hydrosilylated products with high diastereoselectivity.
- O'Neil, Gregory W.,Miller, Michael M.,Carter, Kyle P.
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scheme or table
p. 5350 - 5353
(2011/01/05)
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- Efficient synthesis of α-(hydroxymethyl) ketones not available through aldol-type processes
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An efficient synthesis of α-(hydroxymethyl) ketones from β-keto esters has been developed, which is experimentally simple, amenable to large scale production and provides products of high purity without resort to chromatography in most cases. The method is a useful alternative and complement to condensation processes.
- Hitchcock,Perron,Martin,Albizati
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p. 1059 - 1061
(2007/10/02)
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- Chemistry of aldolate dianions. Effects of β-heteroatom substituents on ketone enolization
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β-Hydroxy ketones can be doubly deprotonated with >2 equiv of an amide base at low temperature providing both proximal or distal aldolate dianions in good to excellent yield. A variety of substitutionally biased β-hydroxy ketones give exclusively distal dianions. If the distal site is blocked, proximal dianions are formed in good yield; however, Chromatographic separation of the silylated products leads to decreased yields. Comparative enolization studies of 4-hydroxy-2-butanone, l-hydroxy-3-pentanone, and hydroxyl-substituted derivatives reveal a kinetic factor favoring proximal deprotonation of β-OTMS and β-alkoxy ketones. However, there is a thermodynamic factor favoring distal dianions that becomes significant as solutions of the dianions are warmed. Thermal stability studies indicate good room temperature stability of the dianions toward elimination and retroaldolization processes; control studies in this area also support the presence of a dianionic species. Precedent suggests that the dianions exist as internally chelated species, and we speculate that ion triplets containing bridging lithiums are good candidates for the structure of both proximal and distal dianion species. The distal dianions undergo clean reaction with aldehydes and acyl cyanides leading to β,β′-dihydroxy ketones and β-hydroxy-β′-oxo ketones, respectively.
- Van Martin,Murray, Desmond H.,Pratt, Norman E.,Zhao, Yun-Bo,Albizati, Kim F.
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p. 6965 - 6978
(2007/10/02)
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