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Abstract: General, high-yielding MAOS protocols for the expedited synthesis of functionalized pyrazolo[1,5-a]pyrimidines and pyrazolo[3,4-b]pyrimidines, as well as their pyrazole precursors, are described amenable to an iterative analogue library synthesis strategy for lead optimization. [Copyright &y& Elsevier]

The optically active lactone 1 can be transformed to a chiral building block or intermediate for constructing carbon skeletons containing either a tertiary or quaternary stereogenic center by taking advantage of the steric bulk as well as the reactivity of a trimethylsilyl group at the β-position of 1. [Copyright &y& Elsevier]

• Chemical synthesis of prostaglandin E2 metabolite "tetranor PGE1". • Heck coupling with acrolein diethyl acetal leads to an ester. • Cuprate conjugate addition to a 2-substited-5-alkoxycylopentenone. • Deuterium labeling affords a standard for a prostaglandin urinary metabolite. Prostaglandin E 2 is produced in response to inflammation, often associated with human disease. As prostaglandins are rapidly metabolized, quantification of end urinary metabolites depend on chemical synthesis of isotopically labeled standards to support metabolite quantification. A concise synthesis of tetranor-PGE 1 is described including a late stage incorporation of an isotopically labeled side-chain. [ABSTRACT FROM AUTHOR]

The study and development of azole-based CYP51 inhibitors is an active area of research across disciplines of biochemistry, pharmacology and infectious disease. Support of in vitro and in vivo studies require the development of robust asymmetric routes to single enantiomer products of this class of compounds. Herein, we describe a scalable and enantioselective synthesis to VNI and VFV, the two potent inhibitors of protozoan sterol 14α-demethylase (CYP51) that are currently under consideration for clinical trials for Chagas disease. A key transformation is the Jacobsen Hydrolytic Kinetic Resolution (HKR) reaction. The utility of the synthetic route is illustrated by the preparation of >25 g quantities of single enantiomers of VNI and VFV. [ABSTRACT FROM AUTHOR]