Phosphorylation Organocatalysts Highly Active by Design

Abstract

The activity of nucleophilic organocatalysts for alcohol/phenol phosphorylation was enhanced through attaching oligoether appendages to a benzyl substituent on imidazole- or aminopyridine-based active units, presumably because of stabilizing n–cation interactions of the ethereal oxygens with the positively charged aza-heterocycle in the catalytic intermediates, and was substantially higher than that of known benchmark catalysts for a range of substrates. Density functional theory calculations and the study of analogues having a lower potential for such stabilizing interactions support our hypothesis.

Controlling the Site Selectivity in Acylations of Amphiphilic Diols: Directing the Reaction toward the Apolar Domain in a Model Diol and the Midecamycin A1 Macrolide Antibiotic

“…As mentioned above, we focused our studies on improving the selectivity favoring the acylation of alcohols at the apolar sites. We hypothesized that slightly changing the design of the catalysts to that recently described for a related reaction, as depicted in Scheme a, will both improve their selectivity due to the increased nucleophilicity (expected because of the replacement of para- and ortho-alkoxyalky substituents on the aromatic ring of benzyl by a properly positioned alkoxy moiety) and simplify their preparation. Two catalysts of the new design, G1­(Im,OC 12 ) and G2­(Im,OC 5 ) , were prepared in four steps, as depicted in Scheme b, compared to seven–eight synthetic steps required to prepare the related catalysts reported in the earlier communication and designated as G1­(C12) and G2­(C5) .…”

“…The synthesis of G1(Im,OC 12 ) followed the recently disclosed route. 36 Synthesis of G2(Im,OC 5 ). Methyl 2,6-Bis(undecan-6-yloxy)benzoate (7).…”

Local Electric Field Modulated Reactivity of Pseudomonas aeruginosa Acid Phosphatase for Enhancing Phosphorylation of l-Ascorbic Acid

“…Phosphorylation can confer unique properties to organic compounds (proteins, amino acids, sugars, and hydroxyl compounds), such as chemical stability, biodegradability, emulsion dispersion, and antistatic properties. − Both chemical and biocatalytic methods have been developed for the phosphorylation reaction. Biocatalytic methods are widely used based on their advantages of high regioselectivity and environmentally friendly processes. − However, biocatalytic phosphorylation has been achieved mainly using kinases, which has limited their application due to the requirement for expensive high-energy phosphate donors (ATP) and narrow substrate spectrum. − By contrast, acid phosphatases (APases; EC 3.1.3.2) can catalyze the phosphorylation reaction using cheap phosphate donors, e.g., pyrophosphate (PPi) or polyphosphates and having a broad substrate spectrum that includes unnatural substrates. − For example, the synthesis of 5′-inosine monophosphate (5-IMP) via APase-catalyzed inosine phosphorylation is a representative case at an industrial scale .…”

Desymmetrization of Diols by Phosphorylation with a Titanium-BINOLate Catalyst

“…In 2014, Spivey and co-workers developed nucleophilic pyridine N -oxides as phosphoryl transfer catalysts utilizing DPCP (and in certain cases O -xylenyl phosphoryl chloride) on a range of alcohols, including amino acid derivatives . More recently, Portnoy and co-workers have published on highly active nucleophilic organocatalysts with DPCP, and Kobayashi and co-workers reported the phosphonylation of alcohols with zinc catalysts . Improved phosphate sources in the enzyme catalyzed phosphorylation of alcohols have also been reported …”