115458-99-6

Usage

Uses

Used in Pharmaceutical Industry:
Methyl (R)-2-(Benzyloxy)propionate is used as a key intermediate in the synthesis of optically active 2-hydroxypropoxyaniline derivatives. These derivatives are crucial for the production of Levofloxacin, a widely used antibiotic, through enzymic or microbial stereoselective hydrolysis of racemic lactic acid esters. This process ensures the creation of the desired enantiomer, which is essential for the drug's efficacy and safety.

Upstream product

• 17392-83-5 (R)-Methyl lactate 
• 100-39-0 benzyl bromide 
• 27871-49-4 (S)-Methyl lactate 
• 81927-55-1 O-benzyl 2,2,2-trichloroacetimidate 
• 67-56-1 methanol 
• 100836-85-9 (R)-2-benzyloxypropionic acid 
• 1096537-55-1 C₄₃H₅₂N₁₀O₁₁ 
• 18107-18-1 diazomethyl-trimethyl-silane 
• 33106-32-0 2-(benzyloxy)propanoic acid 

Downstream Products

• 20736-40-7 2-(benzyloxy)-1,2-diphenylethanone 

Relevant academic research and scientific papers

Providing a New Aniline Bioisostere through the Photochemical Production of 1-Aminonorbornanes

Recent years have witnessed an increasing focus on saturated substructures within drug development as a result of the pharmacokinetic and toxicological benefits correlated with higher saturation content. However, the synthetic challenges presented by densely functionalized saturated architectures generally prohibit their evaluation. The abundance of anilines within high-throughput screening libraries is demonstrative of these competing needs. Anilines are prone to adverse metabolic processing, commonly necessitating re-engineering of a given drug lead to ameliorate CYP450 inhibition and/or glutathione adduction issues, but the ease with which these systems are prepared outweighs the toxicity risks. This article contributes to the need for aniline bioisosteres through the development of a robust, photochemical methodology that supplies 1-aminonorbornanes, saturated bicyclic ring systems that offer similar spatial occupancy to anilines while improving metabolic stability. The chemistry provided herein details an efficient and flexible route toward architecturally distinctive 1-aminonorbornanes through the use of visible-light photoredox catalysis. The incorporation of readily diversifiable functional handles (e.g., -OH, -CO2Me, -NHBoc, -NHCbz) illustrates the potential utility of these 1-aminonorbornanes within drug-discovery programs. Additionally, these motifs offer improved metabolic stability relative to that of their aniline congeners (as demonstrated through microsomal stability assays and metabolite identification efforts), indicating applicability of 1-aminonorbornanes as aniline bioisosteres. This report describes the photochemical conversion of aminocyclopropanes into 1-aminonorbornanes via formal [3 + 2] cycloadditions initiated by homolytic fragmentation of amine radical cation intermediates. Aligning with the modern movement toward sp3-rich motifs in drug discovery, this strategy provides access to a diverse array of substitution patterns on this saturated carbocyclic framework while offering the robust functional-group tolerance (e.g., -OH, -NHBoc) necessary for further derivatization. Evaluating the metabolic stability of selected morpholine-based 1-aminonorbornanes demonstrated a low propensity for oxidative processing and no proclivity toward reactive metabolite formation, suggesting a potential bioisosteric role for 1-aminonorbornanes. Continuous-flow processing allowed for efficient operation on the gram scale, providing promise for translation to industrially relevant scales. This methodology only requires low loadings of a commercially available, visible-light-active photocatalyst and a simple salt; thus, it stays true to sustainability goals while readily delivering saturated building blocks that can reduce metabolic susceptibility within drug development programs.

Synthesis method of (R)-2-benzyloxypropionic acid and intermediate thereof

The invention relates to the technical field of organic synthesis, in particular to a synthesis method of (R)-2-benzyloxypropionic acid and an intermediate thereof. The synthesis method of the intermediate for synthesizing (R)-2-benzyloxypropionic acid comprises the step of adding sodium tert-amyl alcohol into a reaction system of R-methyl lactate and benzyl halogen. According to the synthesis method, the raw materials are easy to obtain and cheap, the production cost can be reduced, meanwhile, flammable, explosive and harmful gas cannot be formed in the reaction process, the safety risk is greatly reduced, and large-scale safety production is facilitated.

COMPOUNDS AND METHODS FOR TARGETED DEGRADATION OF KRAS

Bifunctional compounds, which find utility as modulators of Kirsten ras sarcoma protein (KRas or KRAS), are described herein. In particular, the hetero-bifunctional compounds of the present disclosure contain on one end a moiety that binds to the Von Hippel-Lindau E3 ubiquitin ligase and on the other end a moiety which binds KRas, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The heterobifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Casein kinase 1[epsilon] inhibitor, pharmaceutical composition and application thereof

The invention discloses a novel substituted pyrazolopyrimidine compound for inhibiting the activity of casein kinase 1[epsilon] (CK1[epsilon]), a stereoisomer or a stereoisomer mixture of the novel substituted pyrazolopyrimidine compound, a pharmaceutically acceptable salt or solvate of the novel substituted pyrazolopyrimidine compound, and application of the compound to preparation of medicine for treating diseases, disorders or symptoms benefiting from the inhibition of the activity of casein kinase 1[epsilon] (CK1[epsilon]). The compound has inhibitory activity on CK1[epsilon] kinase, OCI-LY10 cells and Karpas299 cells, shows good anti-tumor activity in an OCI-LY10 subcutaneous xenogeneic model, shows excellent synergistic anti-tumor activity when being combined with a BTK inhibitor, has good pharmacokinetic properties, and can be applied to treatment of diseases, disorders or symptoms, including cancers, autoimmune diseases and the like, which benefit from inhibition of casein kinase 1[epsilon] activity, alone or in combination with other drugs.

MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE

The present disclosure relates to bifunctional compounds, which find utility as modulators of Kirsten rat sarcoma protein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation, accumulation, and/or overactivation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Acyclic 1,4-Stereocontrol via the Allylic Diazene Rearrangement: Development, Applications, and the Essential Role of Kinetic e Stereoselectivity in Tosylhydrazone Formation

We report full details of a method for 1,3-reductive transposition of α-alkoxy-α,β-unsaturated hydrazones to provide E-alkenes with high 1,4-stereocontrol between the two respective allylic stereocenters. The process couples a chelation-controlled reduction of the hydrazone with an in situ allylic strain controlled retro-ene reaction of an allyl diazene, i.e., an allylic diazene rearrangement. Such stereotriads are frequently observed motifs in natural products. We observed a fortuitous kinetic preference for the E-hydrazone geometry during the hydrazonation reaction, as only the E-isomers could undergo chelation-controlled reduction.

COMPOUNDS, COMPOSITIONS, AND METHODS FOR INCREASING CFTR ACTIVITY

The disclosure encompasses compounds having e.g., Formula (la) or (lb), compositions thereof, and methods of modulating CFTR activity. The diclosure also encompasses methods of treating a condition associated with CFTR activity or condition associated with a dysfunction of proteostasis comprising administering to a subject an effective amount of a compound of Formula (I) or (lb).

Divergent Synthesis of Aeruginosins Based on a C(sp3)￡H Activation Strategy

A general and scalable access to the aeruginosin family of marine natural products, exhibiting potent inhibitory activity against serine proteases, is reported. This was enabled by the strategic use of two recently implemented Pd-catalyzed C(sp3)￡H activation reactions. The first method allowed us to obtain the common 2-carboxy-6-hydroxyoctahydroindole (Choi) core of the target molecules on a large scale, whereas the second method provided a rapid and divergent access to various hydroxyphenyllactic (Hpla) subunits, including halogenated ones. This unique strategy, together with an optimization of the fragment coupling sequence allowed the synthesis of four aeruginosins, that is, 98A-C and 298A from the chiral pool. Among them, aeruginosin 298A was synthesized on an unprecedentedly large scale. In addition, halogenated aeruginosins 98A and 98C were synthesized for the first time, thanks to a fine-tuning of the final hydrogenation step. Go natural! A general and scalable access to the aeruginosin family of marine natural products (see graphic), exhibiting potent inhibitory activity against serine proteases, is described. The strategic use of two different Pd-catalyzed C(sp3)￡H activation reactions led to the synthesis of aeruginosins98A-C and 298A.

A general and scalable synthesis of aeruginosin marine natural products based on two strategic C(sp3)-H activation reactions

An efficient and scalable access to the aeruginosin family of marine natural products, which exhibit potent inhibitory activity against serine proteases, is reported. This synthesis was enabled by the strategic use of two different, recently implemented C(sp3)-H activation reactions. The first method led to the common 2-carboxy-6-hydroxyoctahydroindole (Choi) core of the target molecules on a large scale, whereas the second one provided rapid and divergent access to the various hydroxyphenyllactic (Hpla) subunits. This strategy allowed the synthesis of the aeruginosins 98B and 298A, with the latter being obtained in unprecedentedly large quantities.

Enantioselective protonation of α-hetero carboxylic acid-derived ketene disilyl acetals under chiral ionic Bronsted acid catalysis

Highly enantioselective protonation of α-halo and alkoxy carboxylic acid-derived ketene disilyl acetals is achieved by using P-spiro chiral diaminodioxaphosphonium barfate as a Bronsted acid catalyst, where the enantiofacial discrimination by the catalyst mainly stems from the recognition of the electronic difference between two substituents on the ketene disilyl acetal.