A series of 80 7-(het)aryl- and 7-ethynyl-7-deazapurine ribonucleosides bearing a methoxy, methylsulfanyl, methylamino, dimethylamino, methyl, or oxo group at position 6, or 2,6-disubstituted derivatives bearing a methyl or amino group at position 2, were prepared, and the biological activity of the compounds was studied and compared with that of the parent 7-(het)aryl-7-deazaadenosine series. Several of the compounds, in particular 6-substituted 7-deazapurine derivatives bearing a furyl or ethynyl group at position 7, were significantly cytotoxic at low nanomolar concentrations whereas most were much less potent or inactive. Promising activity was observed with some compounds against Mycobacterium bovis and also against hepatitis C virus in a replicon assay.
The
first total synthesis of the potent antibiotic berkeleylactone
A is described in 10 steps with an overall yield of 9.5%. A key step
of our concise route is a late-stage, highly diastereoselective, sulfa-Michael
addition. The 16-membered macrocyclic lactone was formed via ring
closing metathesis and subsequent chemoselective reduction. The absolute
stereochemical configuration was confirmed by single-crystal X-ray
analysis. Synthetic berkeleylactone A was tested against several methicillin-resistant Staphylococcus aureus strains, and its potent antibacterial
activity was verified.
The total syntheses of three enantiomerically pure non-proteinogenic amino acids, l-norvaline, γ-oxonorvaline, and syn-γ-hydroxynorvaline, are reported. The chromatography-free route pivoted on the construction of highly enantiomerically enriched substituted α-amino-γ-oxopentanoic acid, from which all three members were accessed divergently via chemoselective and stereoselective reductions. The rapid synthesis of this key α-amino-γ-oxopentanoic acid was achieved by a highly diastereoselective crystallisation-driven three-component Mannich reaction from the readily available building blocks acetone, glyoxylic acid monohydrate, and (S)-(4-methoxyphenyl)ethylamine. The enantiomeric purity of all target molecules was confirmed by HPLC analysis, either of the amino acids or their derivatives.
Crystallization-induced
diastereomer transformation (CIDT) represents
a highly appealing and convenient synthetic tool. Despite its numerous
advantages, it remains rather rarely used due to its uncertain predictability
to occur. Herein, we describe CIDT based on aza-Michael
reactions of diversely functionalized (E)-3-acylacrylic
acids. This method provides direct access to a broad variety of α-amino
acid derivatives in excellent stereochemical purities.
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