RESUMO
Phosphorylation of alcohols is a fundamentally important reaction in both life science and physical science. Product phosphate monoesters play key roles in living organisms, natural products, pharmaceuticals, and organic materials. Most of the chemical methods to date for synthesizing phosphate monoesters, however, require multistep sequences or are limited to specific types of substrates possibly due to harsh conditions. An alternative way to enable the simple production of phosphate monoesters from highly functionalized precursor alcohols is, thus, highly desired. We report herein a catalytic phosphorylation of alcohols with high functional group tolerance using tetrabutylammonium hydrogen sulfate (TBAHS) and phosphoenolpyruvic acid monopotassium salt (PEP-K) as the catalyst and phosphoryl donor, respectively. This method enables the direct introduction of a nonprotected phosphate group to the hydroxy group of a diverse menu of alcohol substrates, including functionalized small molecules, carbohydrates, and unprotected peptides. Nuclear magnetic resonance, mass spectrometric, and density functional theory analyses suggest that an unprecedented mixed anhydride species, generated from PEP-K and TBAHS, acts as an active phosphoryl donor in this reaction. This operationally simple and chemoselective catalytic phosphorylation allows for the efficient production of densely functionalized O-phosphorylated compounds, which are useful in diverse fields including biology and medicine.
RESUMO
UNLABELLED: Gastro-esophageal reflux disease (GERD) is associated with a decreased salivary flow as well as gastric acid production. This study therefore aimed to investigate functional disorders of salivary glands in patients with GERD. METHODS: Thirty-one consecutive patients with GERD underwent salivary gland scintigraphy. RESULTS: If the results defined the optimal cutoff point for determining the decreased salivary secretion as 51 % in parotid glands and 36 % in submandibular glands, a decreased salivary secretion of right parotid gland, left parotid gland, right submandibular gland, and left submandibular gland was found in 39 %, 32 %, 36 %, and 58 %, respectively. Overall, salivary function disorder of at least one major salivary gland was found in 24 patients (78 %) with GERD. There was no difference in the incidence of impaired salivary function between GERD patients with and without erosive esophagitis. Salivary gland function was more frequently diminished than expected in GERD. We concluded that the presence of impaired salivary gland function was considered to be one of risk factors for developing GERD symptoms.