Tuning properties by programming the surface functional group composition of surface-block dendrimers has been limited to dendrimers with only two types of surface functionality (i.e., surface-diblock dendrimers). The Passerini reaction provides dendrimer products from precursor dendrons in reasonable yields. This proof-of-principle experiment opens the door to making surface-triblock dendrimers.

Dolutegravir (DTG), an important active pharmaceutical ingredient (API) used in combination therapy for the treatment of HIV, has been synthesized in continuous flow. By adapting the reported GlaxoSmithKline process chemistry batch route for Cabotegravir, DTG was produced in 4.5 h in sequential flow operations from commercially available materials. Key features of the synthesis include rapid manufacturing time for pyridone formation, one‐step direct amidation of a functionalized pyridone, and telescoping of multiple steps to avoid isolation of intermediates and enable for greater throughput.

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Attaching dendritically branched side chains to each repeat unit of a linear polymer produces molecular building blocks of nanometer‐sized dimensions called dendronized polymers. The structure of these complex molecular architectures is highly tunable and, therefore, of interest for a wide range of potential applications. The first examples of dendronized polymers prepared by living ring‐opening metathesis polymerization of oxanorbornenedicarboximide macromonomers with poly(alkyl ether) dendrons are reported. Small‐angle X‐ray scattering experiments on bulk samples confirm that the diameter of the individual cylindrical polymers can be tailored by the choice of dendron generation or the length of the hydrocarbon peripheral group. Analysis of the SAXS data based on a core‐shell model indicates that although the diameter of the cylinder increases with generation, the size of the core does not change; this suggests that these dendrons only loosely encapsulate the polymer backbone. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 3221–3239

Dolutegravir (DTG), an important active pharmaceutical ingredient (API) used in combination therapyf or the treatment of HIV,has been synthesized in continuous flow. By adapting the reported GlaxoSmithKline process chemistry batch route for Cabotegravir,D TG was produced in 4.5 hi n sequential flowoperations from commercially available materials.Key features of the synthesis include rapid manufacturing time for pyridone formation, one-step direct amidation of afunctionalized pyridone,and telescoping of multiple steps to avoid isolation of intermediates and enable for greater throughput.

Polymer chemistry has embraced multicomponent reactions for synthesizing multifunctional materials, including structurally perfect multimodal dendrimers. An unexpected substituent effect dramatically shortens the time required for the convergent synthesis of dendrimers via the Passerini three-component reaction.

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Over half of pharmaceuticals, both among the top 100 drugs by prescription totals and new U.S. Food and Drug Administration (FDA) approvals, contain at least one chiral center. Moreover, most new chiral pharmaceuticals are synthesized as a single isomer. Therefore, it is important to be able to determine the primary isomer generated by a synthetic process as well as the presence of any other isomers -preferably directly on the intermediate compounds where each chiral center has been introduced. Molecular rotational spectroscopy, with its sensitivity to small changes in structure and ability to identify compounds directly from electronic structure theory, can be a powerful tool in this application.The present study concerns dolutegravir, an HIV integrase inhibitor developed by GlaxoSmithKline and approved by the FDA in 2013. Efforts are ongoing at the Medicines for All institute in Richmond, Virginia to develop a stereoselective flow synthesis for dolutegravir to reduce its cost and increase availability. a As part of a new route development, an intermediate with two chiral centers was assessed by rotational spectroscopy to determine which diastereomer was the predominant one formed by the process. Notably, NMR was unable to conclusively determine this, but rotational spectroscopy unambiguously determined that the synthetic route produced the correct stereochemistry. This result suggests that rotational spectroscopy can be a useful complement to other analytical characterization methods in organic process development.