ABSTRACT
The non-covalent affinity of a perfluoro chain towards similar has been exploited by many to separate fluorous tagged compounds from non-fluorous compounds by F-SPE or F-LLE. This purification strategy found its application across diverse fields including peptide and oligonucleotide synthesis where even slight inefficient couplings result in deletion sequences that are often difficult to remove from the target sequence. Two commonly employed strategies to address this problem involve end-tagging the target sequence or capping the deletion sequences with fluorous tags. Solution phase syntheses using soluble fluorous supports are easier and quicker. These approaches are reviewed here in detail.
Subject(s)
Chemistry Techniques, Synthetic/methods , Fluorocarbons/chemistry , Oligonucleotides/chemical synthesis , Peptides/chemical synthesis , Amino Acid Sequence , Base Sequence , Molecular Sequence Data , Oligonucleotides/genetics , Peptides/chemistry , SolutionsABSTRACT
A fluorous linker-assisted synthetic protocol has been developed for preparation of sclerotigenin-type benzodiazepine-quinazolinone library containing 144 analogues. Amide coupling of fluorous trimethoxybenzyl (TMB)-protected amino esters with anthranilic acids followed by base-promoted cyclizations afforded 4-benzodiazepine-2,5-diones. Further derivatization of benzodiazepinediones by reacting with azidobenzoyl chlorides, cyclization, and fluorous linker cleavage afforded the desired compound library. The reaction intermediates were purified by fluorous solid-phase extraction (F-SPE) and final products were further purified by prep-HPLC.
Subject(s)
Benzodiazepinones/chemical synthesis , Combinatorial Chemistry Techniques/methods , Fluorine/chemistry , Benzodiazepinones/chemistry , Chromatography, High Pressure Liquid , Molecular StructureABSTRACT
The microbial metabolism of 10-deoxoartemisinin (1), a derivative of the antimalarial drug artemisinin, was investigated. Various strains of fungi were investigated for their ability to transform 1. Of these microorganisms, only Cunninghamella elegans was capable of transforming 1 to 5beta-hydroxy-10-deoxoartemisinin (2), 4alpha-hydroxy-1,10-deoxoartemisinin (3), and 7beta-hydroxy-10-deoxoartemisinin (4). The metabolites 2 and 4 retained an intact peroxide group and are therefore useful scaffolds for synthetic modification in the search for new antimalarial agents.
Subject(s)
Antimalarials/chemistry , Artemisinins/chemistry , Artemisinins/chemical synthesis , Cunninghamella/metabolism , Sesquiterpenes/chemistry , Sesquiterpenes/chemical synthesis , Hydroxylation , Molecular Structure , Mucor/metabolism , Penicillium/metabolism , Stereoisomerism , Structure-Activity RelationshipABSTRACT
The microbial hydroxylation of 10-deoxoartemisinin was investigated with the aim of obtaining preparative yields of hydroxy derivatives. During 14 d at 28 degrees C and pH 6.5 Aspergillus niger transformed 10-deoxoartemisinin (500 mg l(-1)) to 15-hydroxy-10-deoxoartemisinin (26%) and 7beta-hydroxy-10-deoxoartemisinin (69%).
