A5061435381- Synthetic Organic Chemistry Methods
- Carbohydrate Chemistry and Synthesis
- Marine Sponges and Natural Products
- Chemical Synthesis and Analysis
- Oxidative Organic Chemistry Reactions
- Crystallization and Solubility Studies
- Asymmetric Synthesis and Catalysis
- Chemical synthesis and alkaloids
- X-ray Diffraction in Crystallography
- Microbial Natural Products and Biosynthesis
- Catalytic C–H Functionalization Methods
- Chemical Synthesis and Reactions
- Alkaloids: synthesis and pharmacology
- Catalytic Cross-Coupling Reactions
- Axial and Atropisomeric Chirality Synthesis
- Computational Drug Discovery Methods
- Synthesis and pharmacology of benzodiazepine derivatives
- Natural product bioactivities and synthesis
- Plant biochemistry and biosynthesis
- Plant-based Medicinal Research
- HIV/AIDS drug development and treatment
- RNA and protein synthesis mechanisms
- Coordination Chemistry and Organometallics
- Synthesis and Catalytic Reactions
- Fluorine in Organic Chemistry
Amgen (United States)
2022-2023
Bristol-Myers Squibb (United States)
2012-2022
Bristol-Myers Squibb (Germany)
2014-2020
California State Polytechnic University
2015
The Bristol-Myers Squibb Children's Hospital
2013
Scripps Research Institute
2008-2011
University of California, San Diego
2008-2010
We have employed density functional theory (DFT) protocols to calculate the NMR properties of vannusals, a class natural products whose structures been subject recent investigations. The originally assigned structure vannusal B was revised after long synthetic journey which generated series closely related diastereomers. In this work we show how DFT calculations based on functionals and basis sets designed for prediction spectra (M06/pcS-2 level theory) can be used reproduce observed...
Described herein is the synthesis of BMS-986001 by employing two novel organocatalytic transformations: 1) a highly selective pyranose to furanose ring tautomerization access an advanced intermediate, and 2) unprecedented small-molecule-mediated dynamic kinetic resolution variety enantiopure pyranones, one which served as versatile building block for multigram, stereoselective, chromatography-free BMS-986001. The required five chemical transformations resulted in 44% overall yield.
The total synthesis of the originally assigned structure vannusal B (2) and its diastereomer (d-2) are described. Initial forays into these structures with model systems revealed viability a metathesis-based approach SmI2-mediated strategy for key cyclization to forge central region molecule, ring C. former was abandoned in favor latter when more functionalized substrates failed enter process. successful, devised convergent based on closure utilized vinyl iodide (−)-26 aldehyde fragment...
The truth is out there: chase for the originally assigned structure of vannusal B (see structural formula) by total synthesis ended successfully, but created a new puzzle, that true this intriguing marine natural product.
Having determined through total synthesis that the originally assigned structure of vannusals A and B were incorrect, we set out to uncover identity true structures these novel marine natural products. Our search was based on intelligence gathered by NMR spectroscopy chemical took us eight diastereomeric vannusal [2, d-2, 3, d-3, 4, d-4, 5, d-5, Figure 2]. The finally be d-5 d-1, respectively. Their a highly convergent efficient strategy involved fragments vinyl iodide (−)-6 aldehyde (±)-94,...
The intriguing vannusal chemical detective saga based on an interplay between synthesis and NMR spectroscopy finally led to the revision of structure B from 1 2 through total latter. Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted by authors. Please note: publisher is responsible for content functionality any supporting information supplied Any queries (other...
By invalidating two more suspected structures for vannusal B (see C21-epi-1 and C21-epi, C25-epi-1) through their total syntheses, this fascinating study sets the stage demystification of true structure architecturally novel marine natural product its sibling, A. Detailed facts importance to specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted by authors. Please note: The publisher is...
A concise and scalable second generation synthesis of HIV maturation inhibitor BMS-955176 is described. The framed by an oxidation strategy highlighted a CuI mediated aerobic betulin, highly selective PIFA dehydrogenation oxime, subsequent Lossen rearrangement which occurs through unique reaction mechanism for the installation C17 amino functionality. synthetic route proceeds in 7 steps with 47% overall yield begins from abundant inexpensive natural product betulin.
Herein, a novel route to atropisomeric N-aryl quinolones with low rotational barriers is demonstrated, leveraging dual photochemical/organocatalytic approach the required ring closure in up 94% yield and >99% ee. The use of continuous flow system allows for impurity suppression enables rapid scale-up decagram scale.
The direct conversion of a hydroxamic acid to an amine has been accomplished in single step the synthesis HIV drug candidate BMS-955176. This process utilizes catalytic base and proceeds under mild conditions (CH3CN, cat. DBU, 60 °C), without need for strong electrophiles required typical Lossen rearrangements, can be applied aliphatic aromatic acids. Through investigation kinetics this transformation, mechanism was revealed involving novel initiation pathway self-propagation cycle. involves...
Die Wahrheit ist da draußen: Suche nach der ursprünglich zugeordneten Struktur von Vannusal B (siehe Strukturformel) mithilfe Totalsynthese konnte erfolgreich abgeschlossen werden, resultiert aber in einer neuen Frage – wahren dieses marinen Naturstoffs. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted by the authors. Please note: The publisher is...
An efficient, scalable synthesis of (−)-(3R,4R)-1-benzyl-4-(benzylamino)piperidin-3-ol (4) is described. Reduction the pyridinium salt prepared from pyridine and benzyl chloride generated corresponding tetrahydropyridine derivative. A two-stage epoxidation, followed by ring-opening epoxide with BnNH2, established regiochemistry amino alcohol served to set trans-relationship between amine hydroxyl group. The resulting racemic intermediate was then resolved formation (R)-O-acetyl mandelic...
We report use of U-shaped biconically tapered optical fibers (BTOF) as probes for label-free immunoassays. The regions the sensors were functionalized by immobilization immunoglobulin-G (Ig-G) and tested detection anti-IgG at concentrations 50 ng/mL to µg/mL. Antibody-antigen reaction creates a biological nanolayer modifying waveguide structure leading change in sensor signal, which allows real-time monitoring. kinetics antibody (mouse Ig-G)-antigen (rabbit anti-mouse IgG) reactions was...
The development of a convergent route to the NLRP3 (nucleotide-binding domain and leucine-rich repeat-containing protein 3) agonist BMS-986299 is reported. synthesis relies on key Miyaura borylation tandem Suzuki–Miyaura coupling between an iodoimidazole o-aminochloroarene, followed by acid-mediated cyclization afford aminoquinoline core. subsequent Boc cleavage regioselective acylation target compound. Two routes intermediate are presented, along with o-aminochloroarene via Negishi...
Abstract Described herein is the synthesis of BMS‐986001 by employing two novel organocatalytic transformations: 1) a highly selective pyranose to furanose ring tautomerization access an advanced intermediate, and 2) unprecedented small‐molecule‐mediated dynamic kinetic resolution variety enantiopure pyranones, one which served as versatile building block for multigram, stereoselective, chromatography‐free BMS‐986001. The required five chemical transformations resulted in 44 % overall yield.
Zwei weitere vermutete Strukturen ausgeschlossen: Die Totalsynthesen der gezeigten Verbindungen schufen die Grundlage für Aufklärung wahren Struktur des marinen Naturstoffs Vannusal B und seines Verwandten, A. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted by the authors. Please note: The publisher is responsible for content functionality any supporting...
Four synthetic strategies were evaluated towards the preparation of (-)-(3R,4R)-1-benzyl-4-(benzylamino)piperidin-3-ol (1), which was constructed with control over relative and absolute stereochemistry 4,3-amino alcohol moiety. The first strategy employed a novel Rh(I) catalyzed asymmetric hydrogenation, while two other exploited existing in 2-deoxy-D-ribose, fourth explored both biocatalytic classical resolution techniques as means to impart enantioenrichment racemic intermediates en route...
A three-step synthesis of (S)-TRIP enabled by efficient Suzuki cross-coupling conditions using commercial starting materials was developed and demonstrated on a kilogram scale. These novel reaction feature Pd2(dba)3/CataCXium in the presence TBAB KOH provide conversions up to 90% while minimizing formation common byproducts. Following an improved demethylation protocol powerful methanol purification during step 2, high-quality catalyst 99% purity isolated 52% yield over three steps.
Die chemische Detektivgeschichte um die Struktur von Vannusal, das Wechselspiel zwischen chemischer Synthese und NMR-Spektroskopie nutzte, führte schließlich über Totalsynthese 2 zur Revision der Vannusal B 1 zu 2.
An addition of organozinc nucleophiles to N-acyl activated quinolines and isoquinolines is described. Simple transmetalation with the corresponding Grignard reagents using ZnCl2 forms compounds which are functional group tolerant stable reactive acyl chloride for extended periods. A wide variety substrates include electron-withdrawing groups well tolerated form 2-substituted dihydroquinolines dihydroisoquinolines. This methodology has been applied toward an improved synthetic route...
Telescoped synthesis enabled by reaction monitoring.
An expeditious synthesis of an advanced tripeptide intermediate en route to a tubulysin antibody–drug conjugate payload is described. The efficient formation N-propyl tertiary amide required tailoring the amine component reduce steric demand. Additionally, double activation carboxylate was via aluminum–Lewis acid coupled activated ester strategy enable highly congested bond with superior retention stereochemical integrity. Other permutations reactant structure and reagents met failure....
Abstract With the emergence of high-repetition-rate two-dimensional Thomson scattering (TS) measurements, improving spectral data analysis is a key area interest. We present new way to derive electron temperature and density laser-driven blast waves in plasmas from their TS spectra with machine learning (ML). This occurs both non-collective ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mrow> <mml:mi>α</mml:mi> <mml:mo><</mml:mo> </mml:mrow> </mml:math>...