Chemoselective Nozaki-Hiyama-Takai-Kishi and Grignard reaction: short synthesis of some carbahexopyranoses.

A common, divergent, efficient, stereoselective and short approach for the total syntheses of some carbahexopyranoses namely, MK7607, (-)-gabosine A, (-)-conduritol E, (-)-conduritol F, 6a-carba-ß-d-fructopyranose and other carbasugars using chemoselective Grignard or Nozaki-Hiyama-Takai-Kishi (NHTK) reactions and RCM. Herein, the Grignard and NHTK reactions are able to differentiate the reactivity difference between lactol or lactolacetate and aldehyde of 2 & 6 under given conditions to give the desired skeleton chemoselectivity.

Recent Advances in the Development of Pharmaceutical Agents for Metabolic Disorders: A Computational Perspective.

BACKGROUND: Metabolic disorders comprise a set of different disorders varying from epidemic diseases such as diabetes mellitus to inborn metabolic orphan diseases such as phenylketonuria. Despite considerable evidence showing the importance of the computational methods in discovery and development of new pharmaceuticals, there are no systematic reviews outlining how they are utilized in the field of metabolic disorders. This review aims to discuss the necessity of the development of web-based tools and databases by integration of available information for solving Big Data problems in network pharmacology of metabolic disorders. METHODS: We undertook a structured search of bibliographic databases for peer-reviewed research literature using a focused review question and inclusion/exclusion criteria. The quality of retrieved papers was appraised using standard tools. RESULTS: The alterations in metabolic pathways cause various cardiovascular, hematological, neurological, gastrointestinal, immune disorders and cancer. In this regard, informatics, Big Data and modeling techniques aid in the design of novel therapeutic agents for metabolic diseases by addressing various Big Data problems in the network polypharmacology (drugs/pharmaceutical agents, proteins, genes, diseases, bioassays, ADMET and metabolic pathways), identification of privileged scaffolds, developing new diagnostic biomarkers, understanding the pathophysiology of disease and progress in personalized medicine. CONCLUSION: The recent advances of developing pharmaceutical agents for various metabolic disorders by considering their pathogenesis, mechanisms of action, therapeutic and adverse effects have been summarized. We have highlighted the role of computational techniques, drug repurposing, and network-based polypharmacological approaches in the identification of new/existing medicines with improved drug-likeness properties for the rare metabolic disorders.

Palladium-Catalyzed Double Allylation of Sugar-Imines by Employing Tamaru-Kimura's Protocol: Access to Unnatural Iminosugars.

Conversion of vinyl pyranosylamine and vinyl furanosylamines to 2,6- and 2,5-disubstituted pyrrolidine and piperidine iminosugars, respectively, in one pot was developed using Kimura and Tamaru's procedure, where a Pd salt in the presence of Et2Zn was used for the domino reaction. In this procedure, double allylation, which involves nucleophilic allylation-heterocyclization, took place to give desired nitrogen heterocycles. This strategy was further elaborated to synthesize some unnatural deoxycalystegines, hydroxylated pyrrolidines, piperidines, and indolizidine analogues.

DDQ-Promoted Benzylic/Allylic sp(3) C-H Activation for the Stereoselective Intramolecular C-N Bond Formation: Applications to the Total Synthesis of (-)-Codonopsinine, (+)-5-epi-Codonopsinine, (+)-Radicamine B, and (-)-Codonopsinol.

This is the first report on an intramolecular C-N bond formation of an amide-tethered benzylic/allylic system using DDQ under neutral conditions which has been successfully applied to the total synthesis of naturally occurring pyrolidine alkaloids. The key steps for the synthesis of corresponding precursors involve Julia-Kociensky olefination/cross-metathesis and dihydroxylation reactions, and this methodology is also extended to the ω-unsaturated N-sulfanilamide to furnish piperidines.

A short, efficient, and stereoselective total synthesis of a pyrrolidine alkaloid: (-)-codonopsinine.

An efficient total synthesis of antibiotic (-)-codonopsinine 1 with an overall yield of 44% was achieved from d-alanine as a chiral template. The key steps in our strategy are modified Sharpless asymmetric dihydroxylation reaction and the highly stereoselective intramolecular acid-catalyzed amidocyclization.