ABSTRACT
We report the formation and characterization of two diastereomeric thiol-ene addition products of the asthma medication Montelukast within chewing tablets. Widespread tin-based thermal stabilizers dioctyltin bis(2-ethylhexyl thioglycolate) and monooctyltin tris(2-ethylhexyl thioglycolate), used in the manufacturing process of the medication's forming foil, were identified as the source of the thiol reactant, showing that these stabilizers may play a part in the degradation of Montelukast and APIs with functionalities similar to those of Montelukast, which should be considered during development of medication. The isolation and analysis of these impurities was performed by HPLC and UV-vis spectroscopy. HRMS and NMR data were collected to characterize and determine the structures of these compounds.
Subject(s)
Acetates/therapeutic use , Asthma/drug therapy , Cyclopropanes/therapeutic use , Organotin Compounds/chemistry , Quinolines/therapeutic use , Sulfhydryl Compounds/therapeutic use , Sulfides/therapeutic use , Acetates/analysis , Cyclopropanes/analysis , Humans , Molecular Structure , Quinolines/analysis , Sulfhydryl Compounds/analysis , Sulfides/analysis , TemperatureABSTRACT
The enantioselective synthesis of (+)-17-norcharaciol is described. An uncatalyzed intramolecular carbonyl-ene reaction and a ring-closing metathesis were used as key C/C-connecting transformations to assemble the trans-bicyclo[10.3.0]pentadecane norditerpenoid core. We also report the evolution of our synthetic strategy toward the fully substituted characiol skeleton and the experiences from this venture.
Subject(s)
Diterpenes/chemical synthesis , Euphorbia/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Cyclopentanes/chemistry , Diterpenes/isolation & purification , Diterpenes/pharmacology , Esters/chemistry , Humans , Stereoisomerism , Substrate SpecificityABSTRACT
A convergent synthesis of the CDE and CDEF ring systems of pectenotoxin-2 from C and F ring precursors is described.
Subject(s)
Furans/chemical synthesis , Pyrans/chemical synthesis , Furans/chemistry , Ketones/chemistry , Macrolides , Pyrans/chemistryABSTRACT
[reaction: see text] A scalable enantioselective synthesis of the nonnatural 17-norjatrophane diterpene 3-propionyl-15-acetyl-17-norcharaciol is described. Key C/C-connecting transformations are an Evans aldol reaction, an intramolecular carbonyl ene reaction, a Horner-Wadsworth-Emmons olefination, and a ring-closing metathesis for the formation of a 12-membered carbacycle.
