60306-25-4

Upstream product

• 78-83-1 2-methyl-propan-1-ol 
• 358-23-6 trifluoromethylsulfonic anhydride 

Downstream Products

• 262301-37-1 N-[3-(N'-diphenylmethylene)-2-isobutylaminopropionyl] sultam 
• 335197-14-3 (4-methyl-pent-1-ynyloxy)-cyclohexane 
• 104323-07-1 (3R,5S,1'S)-5-<1-<<(tert-butyloxy)carbonyl>amino>-2-phenylethyl>-3-isobutyldihydrofuran-2(3H)-one 
• 1131798-23-6 17-phenyl-13,14-dihydro-trinor-prostaglandin F2α isobutyl ester 
• 170642-24-7 (R)-2-Amino-4-methyl-pentanoic acid ((1S,2S)-2-hydroxy-1-methyl-2-phenyl-ethyl)-methyl-amide 
• 161123-44-0 (3S,5S,6R)-3-Isobutyl-2-oxo-5,6-diphenyl-morpholine-4-carboxylic acid benzyl ester 
• 328-38-1 (R)-leucine 
• 61-90-5 L-leucine 

Relevant academic research and scientific papers

Synthesis and Multiplexed Activity Profiling of Synthetic Acylphloroglucinol Scaffolds

Reported here are novel formic-acid-mediated rearrangements of dearomatized acylphloroglucinols to access a structurally diverse group of synthetic acylphloroglucinol scaffolds (SASs). Density-functional theory (DFT) optimized orbital and stereochemical analyses shed light on the mechanism of these rearrangements. Products were evaluated by multiplexed activity profiling (MAP), an unbiased platform which assays multiple biological readouts simultaneously at single-cell resolution for markers of cell signaling, and can aid in distinguishing genuine activity from assay interference. MAP identified a number of SASs that suppressed pS6 (Ser235/236), a marker for activation of the mTOR and ERK signaling pathways. These results illustrate how biomimetic synthesis and multiplexed activity profiling can reveal the pharmacological potential of novel chemotypes by diversity-oriented synthesis.

Reevaluating the Substrate Specificity of the L-Type Amino Acid Transporter (LAT1)

The L-type amino acid transporter 1 (LAT1, SLC7A5) transports essential amino acids across the blood-brain barrier (BBB) and into cancer cells. To utilize LAT1 for drug delivery, potent amino acid promoieties are desired, as prodrugs must compete with millimolar concentrations of endogenous amino acids. To better understand ligand-transporter interactions that could improve potency, we developed structural LAT1 models to guide the design of substituted analogues of phenylalanine and histidine. Furthermore, we evaluated the structure-activity relationship (SAR) for both enantiomers of naturally occurring LAT1 substrates. Analogues were tested in cis-inhibition and trans-stimulation cell assays to determine potency and uptake rate. Surprisingly, LAT1 can transport amino acid-like substrates with wide-ranging polarities including those containing ionizable substituents. Additionally, the rate of LAT1 transport was generally nonstereoselective even though enantiomers likely exhibit different binding modes. Our findings have broad implications to the development of new treatments for brain disorders and cancer.

Synthesis of quaternary α-methyl α-amino acids by asymmetric alkylation of pseudoephenamine alaninamide pivaldimine

The utility of pseudoephenamine as a chiral auxiliary for the alkylative construction of quaternary α-methyl α-amino acids is demonstrated. The method is notable for the high diastereoselectivities of the alkylation reactions, for its versatility with respect to electrophilic substrate partners, and for its mild hydrolysis conditions, which provide α-amino acids without salt contaminants. Alternatively, α-amino esters can be obtained by direct alcoholysis.

Synthesis of azide-alkyne fragments for 'click' chemical applications. formation of chiral 1,4-disubstituted-(β-alkyl) γ- 1,2,3-triazole scaffolds from orthogonally protected chiral β-alkyl-trialkylsilyl γ- Pentynyl azides and chiral β-alkyl γ- Pentynyl-alcohols

A library of chiral γ-pentynyl alcohols and γ-pentynyl azides was made using the SuperQuat auxiliary. Coupling of the free alkynes with the azides by Huisgen 1,3-dipolar cycloaddition provided chiral oligomeric 1,4-disubstituted-1,2,3-triazoles as possible peptidomimetic compounds.

Diastereoselective synthesis of β2-amino acids

As part of an ongoing project concerning the synthesis of nonnatural amino acids, we have now developed a general strategy for the preparation of β2-amino acids (or 2-aminocarboxylic acid derivatives). Our procedure involves the synthesis of the sultam β-alaninate precursor 5 whose alkylation led with high yields and excellent diastereoselectivity to the precursor of β2-homophenylalanine, β2-homoalanine, and β2-homoleucine. Subsequent deprotection and Boc-protection yielded the expected β2-amino acids. X-ray analysis of the alkylation product established that (-)-sultam yielded (R)-β2-amino acids, conversely (+)-sultam yielded the enantiomer. The topicity of this alkylation is in agreement with the alkylation of Oppolzer's precursor for the synthesis of α-amino acids and opposite to that observed for gem-dialkylation.

ASYMMETRIC SYNTHESIS OF α-AMINO ACIDS BY ALKYLATION OF A GLYCINE AMIDE DERIVATIVE BEARING CHIRAL 2,5-DISUBSTITUTED PYRROLIDINE AS AN AMINE COMPONENT

Highly diastereoselective alkylation (=96percent de) of α-lithiated N-N'-bis(methylthio)-methyleneglycyl)-trans-2,5-bis(methoxymethyl)pyrrolidine and subsequent hydrolysis gave α-amino acids of high optical purity.An unusual amino acid (2S,9S)-2-amino-8-oxo-9,10-epoxydecanoic acid was synthesized in its N-protected form as an application of the method.