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The development of a convergent route to the NLRP3 (nucleotide-binding domain and leucine-rich repeat-containing protein 3) agonist BMS-986299 is reported. The synthesis relies on a key Miyaura borylation and a tandem Suzuki-Miyaura coupling between an iodoimidazole and an

A scalable synthesis of 2-chloro-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)aniline (1), a key intermediate in the synthesis of an immuno-oncology asset, is described. A Negishi cross-coupling...

Since the implementation of forensic DNA typing in labs more than 20 years ago, the analysis procedures and data interpretation have always been conducted in a laboratory by highly trained and qualified scientific personnel. Rapid DNA technology has the potential to expand testing capabilities within forensic laboratories and to allow forensic STR analysis to be performed outside the physical boundaries of the traditional laboratory.The developmental validation of the DNAscan/ANDE Rapid DNA Analysis System was completed using a BioChipSet™ Cassette consumable designed for high DNA content samples, such as single source buccal swabs. A total of eight laboratories participated in the testing which totaled over 2300 swabs, and included nearly 1400 unique individuals. The goal of this extensive study was to obtain, document, analyze, and assess DNAscan and its internal Expert System to reliably genotype reference samples in a manner compliant with the FBI's Quality Assurance Standards (QAS) and the NDIS Operational Procedures.The DNAscan System provided high quality, concordant results for reference buccal swabs, including automated data analysis with an integrated Expert System. Seven external laboratories and NetBio, the developer of the technology, participated in the validation testing demonstrating the reproducibility and reliability of the system and its successful use in a variety of settings by numerous operators. The DNAscan System demonstrated limited cross reactivity with other species, was resilient in the presence of numerous inhibitors, and provided reproducible results for both buccal and purified DNA samples with sensitivity at a level appropriate for buccal swabs. The precision and resolution of the system met industry standards for detection of micro-variants and displayed single base resolution. PCR-based studies provided confidence that the system was robust and that the amplification reaction had been optimized to provide high quality results.The DNAscan integrated Expert System was examined as part of the Developmental Validation and successfully interpreted the over 2000 samples tested with over 99.998% concordant alleles. The system appropriately flagged samples for human review and failed both mixed samples and samples with insufficient genetic information. These results demonstrated the integrated Expert System makes correct allele calls without human intervention.

The large-scale synthesis of ethyl 4-bromocyclohex-3-enecarboxyalate, using a mild brominating reagent derived from triphenyl phosphite and bromine, is reported. The development and comparison of both continuous and batch processes are described. A modified addition sequence was developed based on the knowledge garnered from flow-processing, resulting in a safe and efficient process for the in situ generation of the unstable active reagent and its immediate reaction with the ketone in a batch mode process.

A concise and scalable second generation synthesis of HIV maturation inhibitor BMS-955176 is described. The synthesis is framed by an oxidation strategy highlighted by a CuI mediated aerobic oxidation of betulin, a highly selective PIFA mediated dehydrogenation of an oxime, and a subsequent Lossen rearrangement which occurs through a unique reaction mechanism for the installation of the C17 amino functionality. The synthetic route proceeds in 7 steps with 47% overall yield and begins from the abundant and inexpensive natural product betulin.

The original CODIS database based on 13 core STR loci has been overwhelmingly successful for matching suspects with evidence. Yet there remain situations that argue for inclusion of more loci and increased discrimination. The PowerPlex® Fusion System allows simultaneous amplification of the following loci: Amelogenin, D3S1358, D1S1656, D2S441, D10S1248, D13S317, Penta E, D16S539, D18S51, D2S1338, CSF1PO, Penta D, TH01, vWA, D21S11, D7S820, D5S818, TPOX, DYS391, D8S1179, D12S391, D19S433, FGA, and D22S1045. The comprehensive list of loci amplified by the system generates a profile compatible with databases based on either the expanded CODIS or European Standard Set (ESS) requirements. Developmental validation testing followed SWGDAM guidelines and demonstrated the quality and robustness of the PowerPlex® Fusion System across a number of variables. Consistent and high-quality results were compiled using data from 12 separate forensic and research laboratories. The results verify that the PowerPlex® Fusion System is a robust and reliable STR-typing multiplex suitable for human identification.

Title compound (IX*) is prepared from racemic lactol (I) using small-molecule-mediated dynamic kinetic resolution and a selective pyranose-to-furanose ring contraction as the key steps.

Described herein is the synthesis of BMS-986001 by employing two novel organocatalytic transformations: 1) a highly selective pyranose to furanose ring tautomerization to access an advanced intermediate, and 2) an unprecedented small-molecule-mediated dynamic kinetic resolution to access a variety of enantiopure pyranones, one of which served as a versatile building block for the multigram, stereoselective, and chromatography-free synthesis of BMS-986001. The synthesis required five chemical transformations and resulted in a 44 % overall yield.

Results of an online questionnaire probing audiologists' professional education and clinical practices in central auditory processing and its disorders are reported. Respondents demonstrated scant knowledge of the efficiency of central auditory tests and procedures; however, they were rather consistent in reporting more frequent use of tests and procedures they rated as more efficient. Many of the tests and procedures (including electrophysiologic measures) reported as most frequently used are among those cited in the literature as having good sensitivity and specificity. Respondents recognized the audiologist's treatment responsibilities in the areas of environmental accommodations and assistive listening devices; however, less than half of the respondents judged auditory training to fall within the audiologist's purview. Comparison with a similar study published in 1998 revealed an increase in respondents' academic preparation in (C)APD, with little change in clinical preparation, and use of a more efficient central auditory test battery. Se reportan los resultados de un cuestionario en línea indagando sobre la educación profesional y las prácticas clínicas de los audiólogos en cuanto al procesamiento auditivo (central) y sus trastornos. Aquellos que respondieron demostraron un débil conocimiento sobre la eficiencia de las pruebas y procedimientos auditivos centrales; sin embargo, fueron bastante consistentes en reportar un uso más frecuente de las pruebas y procedimientos que consideraban más eficientes. Muchas de las pruebas y procedimientos (incluyendo las mediciones electrofisiológicas) que se reportaron como más frecuentemente utilizadas, están entre las que se citan en la literatura como de mejor sensibibilidad y especificidad. Los que responsieron reconocieron las responsabilidades en cuanto a tratamiento por parte del audiólogo, en las áreas de adecuación ambiental y en el uso de dispositivos auditivos de apoyo. Sin embargo, menos de la mitad de los que respondieron consideraron que el entrenamiento auditivo estaba dentro de las ámbito del audiólogo. La comparación con un estudio similar publicado en 1998 reveló una mejoría en la preparación académica de los audiológos en (C)APD, con poco cambios en la preparación clínica, y en el uso de una batería mas eficiente de pruebas para audición central.

The fast atom bombardment (FAB) mass spectrometric analysis of several series of ruthenium-bidentate ligand complexes such as (RuLL'L'')X/sub 2/, (RuL/sub 2/L')X/sub 2/, and (RuL/sub 2/L')X/sub 2/, and (RuL/sub 3/)X/sub 2/ are discussed, where L, L', and L'' include 2,2'-bipyridine, 1,10-phenanthroline, their derivatives and related compounds. Surprisingly abundant, intact, doubly charged cations (RuL/sub 3/)/sup 2 +/, (RuLL'L'')/sup 2 +/, and (RuL/sub 2/L')/sup 2 +/ are observed for most complexes studied. Structurally significant fragment ions are generally observed for all complexes in addition to singly charged molecular cationic species such as (RuLL'L'')/sup +/ and (RuLL'L'')X/sup +/. The (RuLL'L'')/sup 2 +//(RuLL'L'')/sup +/ ratio, where L = L' = L'', L = L' not equal to L'', or L not equal to L not equal to L'' depending on the series involved, varies from 3.5 to 0.35 over the 22 complexes studied. Reasons for the observation of these unique abundant doubly charged ions in a FAB spectrum, especially in a nitrobenzyl alcohol matrix, are discussed. Ions indicative of ligand exchange reactions between ruthenium centers are not observed for mixed ligand complexes. 23 references, 4 figures, 1 table.