Sarah J Dolman

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Syntheses and catalytic activities of seven new polymer-supported chiral Mo-based complexes are disclosed. Four of the complexes are polystyrene-based, and three involve polynorbornene supports. Studies concerning the ability of the polymer-bound chiral complexes to promote an assortment of asymmetric ring-closing (ARCM) and ring-opening (AROM) metathesis(More)
A highly efficient synthesis of Vaniprevir (MK-7009) has been accomplished in nine linear steps and 55% overall yield. The key features of this synthesis include a cost-effective synthesis of the isoindoline subunit and efficient construction of the 20-membered macrocyclic core of Vaniprevir (MK-7009) utilizing ring-closing metathesis technology. A(More)
A novel method has been investigated for the selective and sensitive determination of a range of tricyclic antidepressants including amitriptyline, doxepin, nortriptyline, promazine, chlorpromazine, imipramine, clomipramine, desipramine, protriptyline and trimipramine using electrogenerated chemiluminescence (ECL). The ECL mechanism is based on the reaction(More)
A series of stearoyl-CoA desaturase 1 (SCD1) inhibitors were developed. Investigations of enzyme potency and metabolism led to the identification of the thiadiazole-pyridazine derivative MF-438 as a potent SCD1 inhibitor. MF-438 exhibits good pharmacokinetics and metabolic stability, thereby serving as a valuable tool for further understanding the role of(More)
A facile and general protocol for the preparation of 2-amino-1,3,4-oxadiazoles is reported. This method relies on a tosyl chloride/pyridine-mediated cyclization of a thiosemicarbazide, which is readily prepared by acylation of a given hydrazide with the appropriate isothiocyanate. Cyclization of the thiosemicarbazide consistently outperforms the analogous(More)
A facile and general protocol for the preparation of isothiocyanates from alkyl and aryl amines is reported. This method relies on a tosyl chloride mediated decomposition of a dithiocarbamate salt that is generated in situ by treatment of an amine with carbon disulfide and triethylamine. Utilizing this protocol, we have prepared 19-alkyl- and(More)
A novel two-step procedure for the synthesis of 3-amino-5-substituted-isoxazoles is described. In the presence of a base, readily available 3-bromoisoxazolines react with amines to afford 3-aminoisoxazolines. An oxidation protocol was developed for these heterocycles to provide 3-aminoisoxazoles in consistently high yield.
The first catalytic asymmetric ring-closing metathesis method for the synthesis of N-containing heterocycles is reported; this is accomplished through Mo-catalyzed kinetic resolution or desymmetrization of unsaturated amines. Importantly, this catalytic asymmetric method delivers medium-ring unsaturated amines (including eight-membered rings) in high yield,(More)
Practical, chromatography-free syntheses of 5-lipoxygenase inhibitor MK-0633 p-toluenesulfonate (1) are described. The first route used an asymmetric zincate addition to ethyl 2,2,2-trifluoropyruvate followed by 1,3,4-oxadiazole formation and reductive amination as key steps. An improved second route features an inexpensive diastereomeric salt resolution of(More)
The design and optimization of a novel series of renin inhibitor is described herein. Strategically, by committing the necessary resources to the development of synthetic sequences and scaffolds that were most amenable for late stage structural diversification, even as the focus of the SAR campaign moved from one end of the molecule to another, highly(More)