66901-82-4

Upstream product

• 108-24-7 acetic anhydride 
• 96-24-2 3-monochloro-1,2-propanediol 
• 1126-20-1 2-allyloxyphenol 
• 57044-25-4 (R)-oxiranemethanol 
• 6452-72-8 1-(2-allyloxyphenoxy)-2,3-epoxypropane 
• 120-80-9 benzene-1,2-diol 
• 57090-45-6 (2R)-3-chloro-1,2-propanediol 
• 6452-71-7 (-)-Oxprenolol 

Downstream Products

• 335281-01-1 (S)-6-allyl-2-(2,3-ditosyloxypropoxy)phenol 
• 335281-03-3 (S)-2-allyloxy-1-(2,3-ditosyloxypropoxy)benzene 

Relevant academic research and scientific papers

A smart library of epoxide hydrolase variants and the top hits for synthesis of (S)-β-blocker precursors

Microtuning of the enzyme active pocket has led to a smart library of epoxide hydrolase variants with an expanded substrate spectrum covering a series of typical β-blocker precursors. Improved activities of 6- to 430-fold were achieved by redesigning the active site at two predicted hot spots. This study represents a breakthrough in protein engineering of epoxide hydrolases and resulted in enhanced activity toward bulky substrates. Hot pockets: Microtuning of the enzyme active pocket gives a smart library of epoxide hydrolase variants with an expanded substrate spectrum covering a series of typical β-blocker precursors. Improved activities of 6- to 430-fold were achieved by redesigning the active site at two predicted hot spots, and enhanced activity toward bulky substrates was found.

Integrated Chemical Process: Convenient Synthesis of Enantiopure 2-Hydroxymethyl-1,4-benzodioxane Derivatives under Iterative Catalysis of CsF

One-pot processes to enantiopure 2-hydroxymethyl-1,4-benzodioxane derivatives have been established under catalysis of CsF. A sequence of O-alkylation of catechols with enantiopure 3-chloro-1,2-propanediol, tosylation of the alcohol, deprotection of the benzyl ether, and intramolecular etherification can be integrated. The O-alkylation is also feasible with enantiopure oxiranes. All reactions, except debenzylation, are catalyzed by a single catalyst, CsF. The hydrogenative deprotection of the benzyl ether with Pd-C is compatible with the CsF-catalyzed reactions. The integrated protocols give rise not only to compaction of the whole processes but also to increases in overall yields.

CsF in organic synthesis. Regioselective nucleophilic reactions of phenols with oxiranes leading to enantiopure β-blockers

The two modes of the paths in the reaction of oxiranes with phenols are completely controlled by CsF. Glycidyl nosylate undergoes exclusive substitution at the C1 position whereas the ring-opening (C-3 attack) occurs with epichlorohydrin, glycidol, and 1,2-epoxyalkanes. These reactions provide convenient access to enantiopure β-blockers.

N-Dealkylation of oxprenolol: Formation of 3-aryloxypropane-1,2-diol,3-aryloxylactic acid, and 2-aryloxyacetic acid metabolites in the rat

Oxprenolol (1), like related β-adrenergic antagonists, undergoes oxidative N-dealkylation to form the corresponding 3-aryloxypropane-1,2-diol (2), 3-aryloxylactic acid (3), and 2-aryloxyacetic acid (4) metabolites. Compounds 3 and 4 were synthesized by conversion of 2-allyloxyphenol (5) to the aryloxyacetaldehyde 6 and subsequent elaboration to the desired acids. Both acids (3 and 4) and glycol 2 were confirmed as metabolites formed from 1 in vivo in the rat and in vitro in the rat liver 9000 x g supernatant fraction. Incubation of a pseudoracemate of 1, made up of equal molar amounts of (2S)-1-d0 and (2R)-1-d2, showed that 2 and 3 arise principally from (2S)-1 by S/R ratios of ~ 5:1 and 2:1, respectively. On the other hand, acetic acid derivative 4 arises about equally from both enantiomers of 1.