Allen R. Harkness

Synthesis and anticonvulsant activity of 3-aryl-5H-2,3-benzodiazepine ampa antagonists

A novel series of 3-aryl-5H-2,3-benzodiazepines with N-3 aromatic substituents has been synthesized. Good in vivo anticonvulsant activity of the new compounds has been demonstrated employing the maximal electroshock seizure test in mice. Evaluation of a subset of the compounds in the cortical wedge assay confirmed the new structures to be AMPA antagonists.

Substrate acidities and conversion times for reactions of amides with di-tert-butyl bicarbonate

Abstract The conversion time tor 4-dimethylaminopyndine catalysed reaction of amides with di- tert -butyl dicarbonate varies dramatically with substrate acidity. The pK a s in DMSO of some amides are determined to support correlation of reactivity with substrate acidity. Particularly acidic substrates, such as 4-thiazolidinone, readily react with a variety of dialkyl dicarbonates. Less acidic substrates react with Boc 2 O but other dialkyl dicarbonates decompose preferentially.

Synthesis of enantioenriched 4-thiazolidinone (−)-LY213829 by chemoselective benzylamide cleavage in the presence of a C-S bond

Abstract ( R )-2-Methylbenzylamine has been used to covalently “resolve” thiol acid 7 and assemble 4-thiazolidinone 8a in one step. Selective deprotection of the 2-methylbenzylamide using lithium in ammonia/THF has been achieved in the presence of a readily hydrogenolyzed C-S bond. Enantioenriched (−)-LY213829 ( 1 ) of 98% ee has been prepared by this five step route in 25% yield from aldehyde 2 .

Synthesis of 4-thiazolidinones from rhodanines by thiocarbonyl removal

Abstract A new procedure for synthesis of 4-thiazolidinones from readily available rhodanines is reported. Slow addition of the substrate to excess zinc dust in acetic acid at reflux affords the best yields. Identification of dimeric byproducts led to development of a procedure to suppress their formation.

Selective methylphosphonylation of an echinocandin B analog derived from LY303366

Abstract Echinocandin B (ECB) analog 1c was methylphosphonylated with the new reagent dimethyldiphosphonate 7 . Selective functionalization of the phenol group was achieved in the presence of 11 other reactive alcohol and amide groups. The phosphonylation was best conducted in a mixture of THF and DMF using lithium t-butoxide as base. Methylphosphonate diester 1d was deprotected by hydrogenolysis to afford methylphosphonate monoester 1e , a potential prodrug for ECB analog 1c .