126983-64-0

Upstream product

• 1779-51-7 n-butyl(triphenyl)phosphonium bromide 
• 591-31-1 3-methoxy-benzaldehyde 
• 502-56-7 nonanone-5 
• 60441-55-6 1-(3'-methoxyphenyl)-pentan-1-ol 
• 109-72-8 n-butyllithium 
• 125617-35-8 (E)-3-(3-Methoxyphenyl)-2-propen-1-ol 
• 2386-64-3 ethylmagnesium chloride 

Downstream Products

• 20056-57-9 1-methoxy-3-pentylbenzene 
• 1291093-59-8 1-methoxy-5-pentylcyclohexa-1,4-diene 
• 20056-66-0 3-pentyl phenol 

Relevant academic research and scientific papers

Highly Selective and Potent Human β-Secretase 2 (BACE2) Inhibitors against Type 2 Diabetes: Design, Synthesis, X-ray Structure and Structure–Activity Relationship Studies

Herein we present the design, synthesis, and biological evaluation of potent and highly selective β-secretase 2 (memapsin 1, beta-site amyloid precursor protein cleaving enzyme 2, or BACE 2) inhibitors. BACE2 has been recognized as an exciting new target for type 2 diabetes. The X-ray structure of BACE1 bound to inhibitor 2 a {N3-[(1S,2R)-1-benzyl-2-hydroxy-3-[[(1S,2S)-2-hydroxy-1-(isobutylcarbamoyl)propyl]amino]propyl]-5-[methyl(methylsulfonyl)amino]-N1-[(1R)-1-phenylpropyl]benzene-1,3-dicarboxamide} containing a hydroxyethylamine isostere was determined. Based on this structure, a computational docking study was performed which led to inhibitor 2 a-bound BACE2 models. These were used to optimize the potency and selectivity of inhibitors. A systematic structure–activity relationship study led to the identification of determinants of the inhibitors’ potency and selectivity toward the BACE2 enzyme. Inhibitors 2 d [N3-[(1S,2R)-1-benzyl-2-hydroxy-3-[[(1S,2S)-2-hydroxy-1-(isobutylcarbamoyl)pentyl]amino]propyl]-N1-methyl-N1-[(1R)-1-phenylpropyl]benzene-1,3-dicarboxamide; Ki=0.031 nm, selectivity over BACE1: ≈174 000-fold] and 3 l [N1-((2S,3R)-3-hydroxy-1-phenyl-4-((3-(trifluoromethyl)benzyl)amino)butan-2-yl)-N3,5-dimethyl-N3-((R)-1-phenylethyl)isophthalamide; Ki=1.6 nm, selectivity over BACE1: >500-fold] displayed outstanding potency and selectivity. Inhibitor 3 l is nonpeptide in nature and may pave the way to the development of a new class of potent and selective BACE2 inhibitors with clinical potential.

Nickel-Catalyzed Alkylation or Reduction of Allylic Alcohols with Alkyl Grignard Reagents

By choosing different phosphine ligands, nickel-catalyzed selective alkylation and reduction of allylic alcohols with alkyl Grignard reagents were performed. The reaction using Ni(dppe)Cl2 as the catalyst resulted in the cross-coupling of allylic alcohols with primary alkyl Grignard reagents and cyclopropylmagnesium bromide. The reaction catalyzed by the combination of Ni(PCy3)2Cl2 and dcype led to the reduction of allylic alcohols. Secondary alkyl Grignard reagents except cyclopropylmagnesium bromide always led to reduction of allylic alcohols using either Ni(dppe)Cl2 or Ni(PCy3)2Cl2/dcype as the catalyst. In the reductive reaction β-H-containing alkyl Grignard reagents were required.

Alkali base-initiated Michael addition/alkyne carbocyclization cascades

A new cascade reaction involving an intramolecular Michael addition followed by an alkyne carbocyclization is presented. The reaction is promoted by a substoichiometric amount of KHMDS and represents one of the rare examples where the carbocyclization of

A tandem Aldol-Grob reaction of ketones with aromatic aldehydes

Aromatic aldehydes react with ketones to produce (E)-1-aryl-1-alkenesvia a tandem Aldol-Grob cleavage reaction sequence. The reaction, initiated by boron trifluoride, also produces a carboxylic acid fragment.

REDUCTIVE TRANSFORMATIONS WITH TRIMETHYLSILYL CHLORIDE-SODIUM IODIDE. A NEW SYNTHESIS OF 4H-1,3-OXAZINES

1-Arylalkenes and 1-arylalkanols are reduced to arylalkanes on heating with trimethylsilyl chloride/sodium iodide in CH3CN.Under similar conditions enones, dialkylated in the β-position of the double bond, give 4H-1,3-oxazines.