This document summarizes the optimization of an organocatalytic domino Michael-Aldol reaction to synthesize bispirooxindoles. Various cinchona alkaloid derivatives were evaluated as catalysts, with a trifunctional S-binaphthyl diamine catalyst (VIII) giving excellent diastereoselectivity and enantioselectivity. Reaction conditions such as temperature, solvent, and substrate scope were varied, demonstrating good yields and selectivity for a range of substrates. A different protecting group was also investigated, and bispirooxindoles were successfully deprotected to give the corresponding amines in high yields and selectivity.
The big topic of the last few years, the use of small organic molecules to catalyse enantioselective transformations. This lecture will start with proline before moving on to some of MacMillan's contributions to this field and, finally, finish with hydrogen bond catalysts and Brønsted acids.
A look at epothilone A as it includes examples of many different forms of asymmetric synthesis. Also includes a little bit about ring-closing metathesis.
The Mitsunobu reaction allows the conversion of alcohols to various functional groups using trialkyl/triaryl phosphine and dialkyl azodicarboxylate reagents. It proceeds via an oxidation-reduction mechanism. Common applications include esterification, etherification, and N-alkylation reactions. Recent advances have focused on replacing conventional reagents to improve selectivity and yields. The Mitsunobu reaction has been widely used in the synthesis of natural products and pharmaceuticals.
1. The document discusses various techniques for asymmetric synthesis including asymmetric catalytic reduction, oxidation, and hydrogenation.
2. Asymmetric catalytic reduction uses chiral catalysts like RuCl2 [(R)-BINAP] to reduce pro-chiral compounds to chiral products. The Noyori asymmetric hydrogenation reduces β-keto esters.
3. Asymmetric catalytic oxidation uses catalysts like Sharpless epoxidation and Shi epoxidation to oxidize substrates and form enantiopure products. The Jacobsen epoxidation and Sharpless asymmetric dihydroxylation are examples.
Self explanatory really, this lecture looks at chiral auxiliaries. We will concentrate on oxazolidinones in alkylations, aldol reaction and the Diels-Alder reaction. There will be a couple examples of other auxiliaries.
Gives an introduction to total synthesis and why we do it (which reminds me, I must add a picture of Everest, as I think the fact that 'it is there' is the main reason for most syntheses). Then to introduce the topic with a reasonably simple synthesis, we will look at an example of the synthesis of Tamiflu.
Finishing oxidation by looking at the Baeyer-Villiger reaction and then turning our attention to reduction. Once again we will see the usual suspects with a who is who of hydride sources.
This document describes the synthesis of [2.2.1]bicyclo-1,4-bisoxaoline ligands using diastereoselective alkylation reactions. The synthesis starts with esterification of the carboxylic acid groups, followed by alkylation with ethyl aluminum chloride to form the (R,R) and (S,S) ligands in high diastereomeric excess. The ligands are then functionalized through reactions with thionyl chloride and amines to introduce various substituents at R1. Deprotection yields the final ligands with defined stereochemistry and substituents at the backbone, sidechain, and R1 position.
The big topic of the last few years, the use of small organic molecules to catalyse enantioselective transformations. This lecture will start with proline before moving on to some of MacMillan's contributions to this field and, finally, finish with hydrogen bond catalysts and Brønsted acids.
A look at epothilone A as it includes examples of many different forms of asymmetric synthesis. Also includes a little bit about ring-closing metathesis.
The Mitsunobu reaction allows the conversion of alcohols to various functional groups using trialkyl/triaryl phosphine and dialkyl azodicarboxylate reagents. It proceeds via an oxidation-reduction mechanism. Common applications include esterification, etherification, and N-alkylation reactions. Recent advances have focused on replacing conventional reagents to improve selectivity and yields. The Mitsunobu reaction has been widely used in the synthesis of natural products and pharmaceuticals.
1. The document discusses various techniques for asymmetric synthesis including asymmetric catalytic reduction, oxidation, and hydrogenation.
2. Asymmetric catalytic reduction uses chiral catalysts like RuCl2 [(R)-BINAP] to reduce pro-chiral compounds to chiral products. The Noyori asymmetric hydrogenation reduces β-keto esters.
3. Asymmetric catalytic oxidation uses catalysts like Sharpless epoxidation and Shi epoxidation to oxidize substrates and form enantiopure products. The Jacobsen epoxidation and Sharpless asymmetric dihydroxylation are examples.
Self explanatory really, this lecture looks at chiral auxiliaries. We will concentrate on oxazolidinones in alkylations, aldol reaction and the Diels-Alder reaction. There will be a couple examples of other auxiliaries.
Gives an introduction to total synthesis and why we do it (which reminds me, I must add a picture of Everest, as I think the fact that 'it is there' is the main reason for most syntheses). Then to introduce the topic with a reasonably simple synthesis, we will look at an example of the synthesis of Tamiflu.
Finishing oxidation by looking at the Baeyer-Villiger reaction and then turning our attention to reduction. Once again we will see the usual suspects with a who is who of hydride sources.
This document describes the synthesis of [2.2.1]bicyclo-1,4-bisoxaoline ligands using diastereoselective alkylation reactions. The synthesis starts with esterification of the carboxylic acid groups, followed by alkylation with ethyl aluminum chloride to form the (R,R) and (S,S) ligands in high diastereomeric excess. The ligands are then functionalized through reactions with thionyl chloride and amines to introduce various substituents at R1. Deprotection yields the final ligands with defined stereochemistry and substituents at the backbone, sidechain, and R1 position.
The document summarizes key concepts from Lecture Seven on alkenes and alkynes. It discusses hydrogenation of alkenes and alkynes using catalysts like Pd/C, including syn and anti addition. It provides an example of the hydrogenation of resiniferatoxin. It also explains the importance of stereochemistry in hydrogenation reactions and mechanisms of addition. Partial hydrogenation reactions using Lindlar catalyst or Na/NH3 are described. The mechanism of radical additions is shown.
Use of stoichiometric amounts of a chiral source. The usual suspects will be discussed, including borane reagents (mostly pinene derivatives) and the Brown allylation.
The document summarizes the retrosynthetic analysis and total synthesis of the natural product callipeltoside C. The retrosynthesis breaks the molecule down into 3 main fragments - the sugar portion, middle section, and bottom half. The synthesis proceeds by synthesizing each fragment separately and coupling them together, with the sugar portion requiring the most steps due to protecting group manipulation and diastereoselective transformations. The total synthesis takes 18 linear steps to assemble all the fragments and achieve the target natural product.
Proteins are composed of amino acids linked together by peptide bonds. There are 20 standard amino acids that make up proteins. Amino acids have different properties depending on their side chains, which can be nonpolar, polar, acidic, or basic. When amino acids join together via peptide bonds, they form the primary structure of proteins. The peptide bond is planar and rigid, giving proteins their distinctive 3D structures.
The document discusses the concept of substrate control in directed epoxidation reactions. It shows that when performing epoxidation reactions on substrates containing multiple oxidizable positions, the reaction preferentially forms epoxides at positions that minimize 1,3-allylic strain. Substrate control allows for high regioselectivity in epoxidation based on sterics and substrate conformation. Directed epoxidation reactions can achieve up to 99:1 regioselectivity through substrate control and transition state stabilization.
The document provides information about various carbon-carbon bond forming reactions including the aldol reaction, Claisen condensation, Dieckmann cyclization, Robinson annulation, and the Hajos-Parrish-Eder-Sauer-Wiechert reaction. It discusses how to control the chemoselectivity of reactions and outlines strategies like choosing the correct nucleophile or pre-forming enolates. Functional groups in specific arrangements like a 1,3-diol relationship indicate certain reaction types. The key message is that retrosynthesis involves recognizing underlying patterns in molecular structures.
The document summarizes the chemistry of azoxy compounds, which contain the azoxy functional group. Azoxyalkanes are generally very stable to heat and light and do not readily undergo reactions like loss of nitrogen. However, intramolecular radical reactions of azoxy compounds can generate cyclic aminyl nitroxides or hydrazyls. The azoxy group stabilizes attached carbon-centered radicals, but the chemistry of α-azoxy radicals is not fully understood. Thermolysis of azoxy compounds usually does not lead to loss of nitrogen dioxide, and instead forms amine oxides or stabilized radicals through rearrangement.
This document provides a summary of dienes and alkynes. It discusses resonance stabilization of conjugated dienes and their regioisomers when undergoing electrophilic addition. For alkynes, it covers their lack of acidity due to their sp hybridization and decreasing acid strength. It also summarizes the hydration of alkynes, which proceeds by a Markovnikov addition through a mercurinium ion intermediate and tautomerizes to the enol form.
BITS - Introduction to Mass Spec data generationBITS
Mass spectrometry is a technique that analyzes molecules based on their mass-to-charge ratio. It involves ionizing samples using sources like MALDI or ESI, separating the ions using mass analyzers like time-of-flight or quadrupole, and detecting the ions. Tandem mass spectrometry allows targeted fragmentation of selected ions to gain additional structural information. Amino acids are the building blocks of proteins and contain variable side chains attached to a common peptide backbone. Mass spectrometry is useful for analyzing proteins and peptides.
Here is a brief overview of some of my work at Mayo Clinic Jacksonville, where I worked in the Organic Synthesis Core Facility for the little over two years between my undergraduate education and graduate school.
This document discusses functional group interconversions, specifically focusing on sulfonate esters. It provides information on common sulfonate leaving groups like tosyl, mesyl, and triflate groups and their relative reactivities. It also discusses the mechanisms and standard methods for preparing sulfonate esters from alcohols using these strong acidic leaving groups, noting that pyridine cannot deprotonate an alcohol directly due to pKa differences.
This document discusses using surface-enhanced Raman spectroscopy (SERS) to detect chemical agents and their hydrolysis products in water at very low (part-per-billion) concentrations in less than 10 minutes. SERS provides high specificity and sensitivity to identify chemicals without false positives. The approach uses functionalized sol-gel SERS capillaries to extract and pre-concentrate samples for fast, on-site analysis at part-per-billion levels for chemicals like cyanide, thiodiglycol, and methyl phosphonic acid in under a minute. Future work involves continuous monitoring of water supplies using a SERS sensor connected to a flow system.
Told you that this was the important one. This weeks reagents include more enolates and then reactions with the C=O group including the such classics as the Wittig reaction.
The document summarizes key concepts about alkene reactions:
1) Markovnikov addition results in the addition occurring on the carbon with the most hydrogen substituents, giving the more substituted primary carbocation which is most stable.
2) Hydroboration follows anti-Markovnikov addition, with the BH3 group adding to the less substituted carbon. Oxidation then occurs with H2O2/NaOH through a 1,2-shift to give anti-Markovnikov addition.
3) Organoboranes are unstable and hydroboration involves coordination of BH3 to the alkene, allowing for stereospecific anti-Markovnikov addition
Finishing off the reactions of carboxylic acid derivatives (well the substitution reactions) and introducing oxidation and reduction. Then looking at the oxidation of alkenes (epoxidation and dihydroxylation) and alcohols (the usual suspects).
This document summarizes reactions of alkenes including:
1. Addition of bromine to form bromonium ions and give anti-addition of bromine with stereospecificity.
2. Diol formation from epoxide ring opening, KMnO4 oxidation, and hydroboration-hydration which can give stereospecific or racemic mixtures.
3. Examples of biologically active natural products formed from alkene reactions like epothilones and dynemicin A.
PhytoQuest owns science to innovate natural ingredients and compounds in the high-margin healthy-living products emerging from the convergence of food, pharmaceuticals, and cosmetics. The company was founded in 1999 as a spin-off focusing on plant-derived, water-soluble components. PhytoQuest maintains several compound libraries containing over 1,100 novel and commercially available compounds for screening purposes. Examples of areas of focus and expertise include iminosugars, which are sugar analogs that can act as glycosylation inhibitors or immune modulators, and certain compounds like casuarines that show promise in modulating immune responses and exhibiting anti-cancer activity.
This document discusses alcohols (compounds containing an -OH functional group). It covers alcohol nomenclature, properties, synthesis, and metabolism.
Alcohols are named based on the parent alkane chain containing the -OH group. They exhibit hydrogen bonding which increases their melting/boiling points and water solubility. Common synthesis methods include SN1/SN2 reactions of alcohols, reduction of carbonyls using NaBH4 or LiAlH4, and reactions of organometallics like Grignard reagents with carbonyls. Ethanol is metabolized in the body through oxidation reactions and excretion primarily through the lungs and urine. Adverse effects of alcohol abuse include
The document describes improvements made to the process for manufacturing the potential therapeutic compound ELN 296571. It summarizes the original multi-step synthesis route and key intermediate compound ELN 361973. The route was optimized to require fewer steps and produce ELN 361973 in higher yields and purity. Later, production of the important intermediate ELN 361973 was outsourced to improve the overall process.
The document summarizes key concepts from Lecture Seven on alkenes and alkynes. It discusses hydrogenation of alkenes and alkynes using catalysts like Pd/C, including syn and anti addition. It provides an example of the hydrogenation of resiniferatoxin. It also explains the importance of stereochemistry in hydrogenation reactions and mechanisms of addition. Partial hydrogenation reactions using Lindlar catalyst or Na/NH3 are described. The mechanism of radical additions is shown.
Use of stoichiometric amounts of a chiral source. The usual suspects will be discussed, including borane reagents (mostly pinene derivatives) and the Brown allylation.
The document summarizes the retrosynthetic analysis and total synthesis of the natural product callipeltoside C. The retrosynthesis breaks the molecule down into 3 main fragments - the sugar portion, middle section, and bottom half. The synthesis proceeds by synthesizing each fragment separately and coupling them together, with the sugar portion requiring the most steps due to protecting group manipulation and diastereoselective transformations. The total synthesis takes 18 linear steps to assemble all the fragments and achieve the target natural product.
Proteins are composed of amino acids linked together by peptide bonds. There are 20 standard amino acids that make up proteins. Amino acids have different properties depending on their side chains, which can be nonpolar, polar, acidic, or basic. When amino acids join together via peptide bonds, they form the primary structure of proteins. The peptide bond is planar and rigid, giving proteins their distinctive 3D structures.
The document discusses the concept of substrate control in directed epoxidation reactions. It shows that when performing epoxidation reactions on substrates containing multiple oxidizable positions, the reaction preferentially forms epoxides at positions that minimize 1,3-allylic strain. Substrate control allows for high regioselectivity in epoxidation based on sterics and substrate conformation. Directed epoxidation reactions can achieve up to 99:1 regioselectivity through substrate control and transition state stabilization.
The document provides information about various carbon-carbon bond forming reactions including the aldol reaction, Claisen condensation, Dieckmann cyclization, Robinson annulation, and the Hajos-Parrish-Eder-Sauer-Wiechert reaction. It discusses how to control the chemoselectivity of reactions and outlines strategies like choosing the correct nucleophile or pre-forming enolates. Functional groups in specific arrangements like a 1,3-diol relationship indicate certain reaction types. The key message is that retrosynthesis involves recognizing underlying patterns in molecular structures.
The document summarizes the chemistry of azoxy compounds, which contain the azoxy functional group. Azoxyalkanes are generally very stable to heat and light and do not readily undergo reactions like loss of nitrogen. However, intramolecular radical reactions of azoxy compounds can generate cyclic aminyl nitroxides or hydrazyls. The azoxy group stabilizes attached carbon-centered radicals, but the chemistry of α-azoxy radicals is not fully understood. Thermolysis of azoxy compounds usually does not lead to loss of nitrogen dioxide, and instead forms amine oxides or stabilized radicals through rearrangement.
This document provides a summary of dienes and alkynes. It discusses resonance stabilization of conjugated dienes and their regioisomers when undergoing electrophilic addition. For alkynes, it covers their lack of acidity due to their sp hybridization and decreasing acid strength. It also summarizes the hydration of alkynes, which proceeds by a Markovnikov addition through a mercurinium ion intermediate and tautomerizes to the enol form.
BITS - Introduction to Mass Spec data generationBITS
Mass spectrometry is a technique that analyzes molecules based on their mass-to-charge ratio. It involves ionizing samples using sources like MALDI or ESI, separating the ions using mass analyzers like time-of-flight or quadrupole, and detecting the ions. Tandem mass spectrometry allows targeted fragmentation of selected ions to gain additional structural information. Amino acids are the building blocks of proteins and contain variable side chains attached to a common peptide backbone. Mass spectrometry is useful for analyzing proteins and peptides.
Here is a brief overview of some of my work at Mayo Clinic Jacksonville, where I worked in the Organic Synthesis Core Facility for the little over two years between my undergraduate education and graduate school.
This document discusses functional group interconversions, specifically focusing on sulfonate esters. It provides information on common sulfonate leaving groups like tosyl, mesyl, and triflate groups and their relative reactivities. It also discusses the mechanisms and standard methods for preparing sulfonate esters from alcohols using these strong acidic leaving groups, noting that pyridine cannot deprotonate an alcohol directly due to pKa differences.
This document discusses using surface-enhanced Raman spectroscopy (SERS) to detect chemical agents and their hydrolysis products in water at very low (part-per-billion) concentrations in less than 10 minutes. SERS provides high specificity and sensitivity to identify chemicals without false positives. The approach uses functionalized sol-gel SERS capillaries to extract and pre-concentrate samples for fast, on-site analysis at part-per-billion levels for chemicals like cyanide, thiodiglycol, and methyl phosphonic acid in under a minute. Future work involves continuous monitoring of water supplies using a SERS sensor connected to a flow system.
Told you that this was the important one. This weeks reagents include more enolates and then reactions with the C=O group including the such classics as the Wittig reaction.
The document summarizes key concepts about alkene reactions:
1) Markovnikov addition results in the addition occurring on the carbon with the most hydrogen substituents, giving the more substituted primary carbocation which is most stable.
2) Hydroboration follows anti-Markovnikov addition, with the BH3 group adding to the less substituted carbon. Oxidation then occurs with H2O2/NaOH through a 1,2-shift to give anti-Markovnikov addition.
3) Organoboranes are unstable and hydroboration involves coordination of BH3 to the alkene, allowing for stereospecific anti-Markovnikov addition
Finishing off the reactions of carboxylic acid derivatives (well the substitution reactions) and introducing oxidation and reduction. Then looking at the oxidation of alkenes (epoxidation and dihydroxylation) and alcohols (the usual suspects).
This document summarizes reactions of alkenes including:
1. Addition of bromine to form bromonium ions and give anti-addition of bromine with stereospecificity.
2. Diol formation from epoxide ring opening, KMnO4 oxidation, and hydroboration-hydration which can give stereospecific or racemic mixtures.
3. Examples of biologically active natural products formed from alkene reactions like epothilones and dynemicin A.
PhytoQuest owns science to innovate natural ingredients and compounds in the high-margin healthy-living products emerging from the convergence of food, pharmaceuticals, and cosmetics. The company was founded in 1999 as a spin-off focusing on plant-derived, water-soluble components. PhytoQuest maintains several compound libraries containing over 1,100 novel and commercially available compounds for screening purposes. Examples of areas of focus and expertise include iminosugars, which are sugar analogs that can act as glycosylation inhibitors or immune modulators, and certain compounds like casuarines that show promise in modulating immune responses and exhibiting anti-cancer activity.
This document discusses alcohols (compounds containing an -OH functional group). It covers alcohol nomenclature, properties, synthesis, and metabolism.
Alcohols are named based on the parent alkane chain containing the -OH group. They exhibit hydrogen bonding which increases their melting/boiling points and water solubility. Common synthesis methods include SN1/SN2 reactions of alcohols, reduction of carbonyls using NaBH4 or LiAlH4, and reactions of organometallics like Grignard reagents with carbonyls. Ethanol is metabolized in the body through oxidation reactions and excretion primarily through the lungs and urine. Adverse effects of alcohol abuse include
The document describes improvements made to the process for manufacturing the potential therapeutic compound ELN 296571. It summarizes the original multi-step synthesis route and key intermediate compound ELN 361973. The route was optimized to require fewer steps and produce ELN 361973 in higher yields and purity. Later, production of the important intermediate ELN 361973 was outsourced to improve the overall process.
The Beckman rearrangement is an acid-catalyzed rearrangement of oximes to substituted amides or lactams. Oximes are compounds derived from aldehydes and ketones that contain a C=N-OH grouping. Ketoximes undergo the Beckman rearrangement in the presence of acids, yielding an acid-amide product through an intramolecular rearrangement. The reaction proceeds through a nitrilium ion intermediate formed by alkyl migration and hydroxyl group expulsion, followed by hydrolysis to form the final amide product.
This is the biggy, the one everyone wants to achieve. Here we will be looking at metal-based chiral catalysis. We will concentrate on bisoxazoline-based Lewis acid catalysis and then look at reductions before finishing with the ubiquitous Sharpless epoxidation and dihydroxylation.
The document lists 12 chemical reactions and asks the reader to identify missing dipoles, dipolarophiles, and cycloducts in each case. The reactions involve azide substitutions, halogenations, nitrene additions, and 1,3-dipolar cycloadditions to form five-membered heterocycles. Key intermediates and products include azides, nitriles, oxazoles, isoxazoles, and triazoles.
IOSRPHR(www.iosrphr.org) IOSR Journal of Pharmacyiosrphr_editor
The document describes the synthesis and pharmacological screening of benzoxazole derivatives as potential anti-inflammatory agents. A series of N'-[substituted sulfonyl]-1,3-benzoxazole-5-carbohydrazide compounds were synthesized using a multi-step synthesis route involving nitration, reduction, acid reactions, and substitution. The compounds were characterized using methods like IR, 1H NMR and mass spectroscopy. The compounds were then screened for anti-inflammatory activity and approximate toxicity. Eight compounds were synthesized with different R1 and R2 substituents on the benzoxazole ring. Preliminary pharmacological screening found some compounds showed promising anti-inflammatory activity with low toxicity, making them potential
IOSRPHR(www.iosrphr.org) IOSR Journal of Pharmacyiosrphr_editor
The document summarizes the synthesis and pharmacological screening of some benzoxazole derivatives as anti-inflammatory agents. A series of new 5-substituted benzoxazoles were synthesized and characterized. These compounds were then screened for their anti-inflammatory activity. Eight compounds (VIa-VIh) with different substituents were synthesized using an appropriate synthetic route. These compounds were purified and their structures were confirmed through various analytical techniques. The compounds were then evaluated for their anti-inflammatory potential through preliminary pharmacological screening tests.
The document discusses the synthetic, analytical, and therapeutic aspects of the pyrazole heterocyclic nucleus. Pyrazole rings are found in many pharmaceutical drugs due to their ease of preparation and important biological activities. Some key points:
- Pyrazoles have anti-inflammatory, antipyretic, antimicrobial, anticancer, and other therapeutic properties.
- They contain an NH group that allows for hydrogen bonding and complex formation.
- Reduction or oxidation at nitrogen atoms in the ring can yield derivative structures.
- Many established drug molecules contain the pyrazole nucleus, including celecoxib, phenylbutazone, and apixaban.
The Mannich reaction involves the condensation of an enolizable carbonyl compound, an aldehyde such as formaldehyde, and a primary or secondary amine. This results in an aminoalkylation and formation of a β-aminocarbonyl compound known as a Mannich base. Modifications using preformed Mannich bases and reactive substrates extend the scope and selectivity of the reaction. The Mannich reaction has wide applications in organic synthesis and for producing natural and medicinal compounds.
This chapter outline discusses DNA and RNA structure and function, including:
- The discovery that DNA is the genetic material through experiments with viruses.
- The double helix structure of DNA determined by Watson and Crick based on data from Franklin and others.
- DNA replication through semiconservative replication to produce identical copies.
- Transcription of DNA to mRNA and the three types of RNA (mRNA, tRNA, rRNA).
- Translation of mRNA using tRNA to specify amino acid sequence and produce proteins according to the genetic code.
1.[1 9]use of 2-{[5-(2-amino-4-oxoquinazolin-3(4 h)-yl)-1,3,4-thiadiazol-2-yl...Alexander Decker
This document describes the synthesis of novel quinazolinone derivatives. Specifically, it details:
1) The synthesis of compound 1 which serves as the starting material.
2) The reaction of compound 1 with various reagents to yield Schiff bases, cyclic, and acyclic derivatives. This includes reactions with aldehydes, ketones, chloroacetyl chloride, and various nucleophiles.
3) Characterization of the synthesized derivatives using techniques like IR, mass, 1H-NMR, and elemental analysis to confirm their structures.
The goal is to gain a better understanding of the reaction pathways and structure-property relationships of these quinazolinone derivatives which have potential biological activities
IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research...iosrphr_editor
This document describes the docking, synthesis, antimicrobial screening, and beta lactamase inhibitory activity of 3-(4-fluorophenylimino) indolin-2-one and 5-chloro-3-(4-fluorophenylimino) indolin-2-one derivatives. Various derivatives were synthesized and their structures were characterized. The derivatives were screened for antimicrobial activity against various microorganisms and for beta lactamase inhibitory activity. Compound IIh, 5-chloro-3-(4-fluorophenylimino)-1-(morpholinomethyl)indolin-2-one, showed the best activity in both the antimicrobial and beta lactamase screens based on its docking results
The document discusses carbenes, which are molecules containing a neutral carbon atom with two unshared valence electrons. Carbenes can be classified as singlets or triplets based on their electronic structure. The document also describes the Wolff rearrangement, where α-diazoketones lose nitrogen to form reactive ketenes. Some applications of the Wolff rearrangement include the synthesis of carboxylic acid analogues, acid amides from carboxylic acids, and esters from carboxylic acids.
A pharmaceutical Chemist shares a view of organic chemistry and his role preparing enantiomeric drugs for clinical trials. Dr. Welch is also on the Titan Explorer team looking for signs of life on other planets
This document discusses the antibiotic tetracycline. It belongs to a group of antibiotics called tetracyclines which are obtained through fermentation of Streptomyces bacteria. Tetracycline has a complex stereochemistry and exists as a zwitterion. It works by inhibiting bacterial protein synthesis by binding to the 30S ribosomal subunit. It is stable under acidic conditions but forms anhydrotetracycline, while under basic conditions it opens to form isotetracycline. It forms insoluble chelates with metals. Tetracycline has broad-spectrum activity against many gram-positive and gram-negative bacteria.
The document discusses the stability of pharmaceutical formulations. It defines stability as a formulation remaining within its physical, chemical, microbiological, therapeutic and toxicological specifications. Stability is important to ensure drug products maintain quality and intended effects until expiration. Chemical and physical degradation pathways include hydrolysis, oxidation, photodegradation, and interactions with excipients or other drugs. Factors like temperature, pH, moisture, and light can affect the rate of degradation. The document focuses on hydrolysis and oxidation as two major degradation pathways and provides examples of each.
This document discusses purine and pyrimidine metabolism. It covers the biosynthesis of purines through 11 steps, degradation of purines to uric acid, medical conditions related to purine metabolism like Lesch-Nyhan and ADA deficiency, the causes and treatment of gout, and drugs used to treat gout like colchicine, probenecid, and allopurinol.
This document discusses metrics for measuring green chemistry performance in the pharmaceutical industry. It notes that pharmaceutical processes are complex, involving multiple reaction stages and waste streams. The author advocates asking the right questions to define appropriate metrics, as there are many options. Key lessons are that analysis provides value and positive change is possible through establishing the right process measures from early stages of development.
The document discusses step-growth polymerization and the development of important polymers like nylon 6,6 and polyesters. It describes how Wallace Carothers at DuPont synthesized nylon 6,6 from adipic acid and hexamethylenediamine to produce the first fully synthetic fiber. Later researchers developed other nylons like nylon 6 from caprolactam and Kevlar from aromatic monomers. Polyesters were also improved through the use of terephthalic acid to increase stiffness and melting point, allowing poly(ethylene terephthalate) or PET to be used for fibers.
Similar to Single multifunctional organocatalyst (20)
UiPath Test Automation using UiPath Test Suite series, part 6DianaGray10
Welcome to UiPath Test Automation using UiPath Test Suite series part 6. In this session, we will cover Test Automation with generative AI and Open AI.
UiPath Test Automation with generative AI and Open AI webinar offers an in-depth exploration of leveraging cutting-edge technologies for test automation within the UiPath platform. Attendees will delve into the integration of generative AI, a test automation solution, with Open AI advanced natural language processing capabilities.
Throughout the session, participants will discover how this synergy empowers testers to automate repetitive tasks, enhance testing accuracy, and expedite the software testing life cycle. Topics covered include the seamless integration process, practical use cases, and the benefits of harnessing AI-driven automation for UiPath testing initiatives. By attending this webinar, testers, and automation professionals can gain valuable insights into harnessing the power of AI to optimize their test automation workflows within the UiPath ecosystem, ultimately driving efficiency and quality in software development processes.
What will you get from this session?
1. Insights into integrating generative AI.
2. Understanding how this integration enhances test automation within the UiPath platform
3. Practical demonstrations
4. Exploration of real-world use cases illustrating the benefits of AI-driven test automation for UiPath
Topics covered:
What is generative AI
Test Automation with generative AI and Open AI.
UiPath integration with generative AI
Speaker:
Deepak Rai, Automation Practice Lead, Boundaryless Group and UiPath MVP
Alt. GDG Cloud Southlake #33: Boule & Rebala: Effective AppSec in SDLC using ...James Anderson
Effective Application Security in Software Delivery lifecycle using Deployment Firewall and DBOM
The modern software delivery process (or the CI/CD process) includes many tools, distributed teams, open-source code, and cloud platforms. Constant focus on speed to release software to market, along with the traditional slow and manual security checks has caused gaps in continuous security as an important piece in the software supply chain. Today organizations feel more susceptible to external and internal cyber threats due to the vast attack surface in their applications supply chain and the lack of end-to-end governance and risk management.
The software team must secure its software delivery process to avoid vulnerability and security breaches. This needs to be achieved with existing tool chains and without extensive rework of the delivery processes. This talk will present strategies and techniques for providing visibility into the true risk of the existing vulnerabilities, preventing the introduction of security issues in the software, resolving vulnerabilities in production environments quickly, and capturing the deployment bill of materials (DBOM).
Speakers:
Bob Boule
Robert Boule is a technology enthusiast with PASSION for technology and making things work along with a knack for helping others understand how things work. He comes with around 20 years of solution engineering experience in application security, software continuous delivery, and SaaS platforms. He is known for his dynamic presentations in CI/CD and application security integrated in software delivery lifecycle.
Gopinath Rebala
Gopinath Rebala is the CTO of OpsMx, where he has overall responsibility for the machine learning and data processing architectures for Secure Software Delivery. Gopi also has a strong connection with our customers, leading design and architecture for strategic implementations. Gopi is a frequent speaker and well-known leader in continuous delivery and integrating security into software delivery.
GraphSummit Singapore | The Future of Agility: Supercharging Digital Transfor...Neo4j
Leonard Jayamohan, Partner & Generative AI Lead, Deloitte
This keynote will reveal how Deloitte leverages Neo4j’s graph power for groundbreaking digital twin solutions, achieving a staggering 100x performance boost. Discover the essential role knowledge graphs play in successful generative AI implementations. Plus, get an exclusive look at an innovative Neo4j + Generative AI solution Deloitte is developing in-house.
Full-RAG: A modern architecture for hyper-personalizationZilliz
Mike Del Balso, CEO & Co-Founder at Tecton, presents "Full RAG," a novel approach to AI recommendation systems, aiming to push beyond the limitations of traditional models through a deep integration of contextual insights and real-time data, leveraging the Retrieval-Augmented Generation architecture. This talk will outline Full RAG's potential to significantly enhance personalization, address engineering challenges such as data management and model training, and introduce data enrichment with reranking as a key solution. Attendees will gain crucial insights into the importance of hyperpersonalization in AI, the capabilities of Full RAG for advanced personalization, and strategies for managing complex data integrations for deploying cutting-edge AI solutions.
In his public lecture, Christian Timmerer provides insights into the fascinating history of video streaming, starting from its humble beginnings before YouTube to the groundbreaking technologies that now dominate platforms like Netflix and ORF ON. Timmerer also presents provocative contributions of his own that have significantly influenced the industry. He concludes by looking at future challenges and invites the audience to join in a discussion.
Communications Mining Series - Zero to Hero - Session 1DianaGray10
This session provides introduction to UiPath Communication Mining, importance and platform overview. You will acquire a good understand of the phases in Communication Mining as we go over the platform with you. Topics covered:
• Communication Mining Overview
• Why is it important?
• How can it help today’s business and the benefits
• Phases in Communication Mining
• Demo on Platform overview
• Q/A
Sudheer Mechineni, Head of Application Frameworks, Standard Chartered Bank
Discover how Standard Chartered Bank harnessed the power of Neo4j to transform complex data access challenges into a dynamic, scalable graph database solution. This keynote will cover their journey from initial adoption to deploying a fully automated, enterprise-grade causal cluster, highlighting key strategies for modelling organisational changes and ensuring robust disaster recovery. Learn how these innovations have not only enhanced Standard Chartered Bank’s data infrastructure but also positioned them as pioneers in the banking sector’s adoption of graph technology.
Introducing Milvus Lite: Easy-to-Install, Easy-to-Use vector database for you...Zilliz
Join us to introduce Milvus Lite, a vector database that can run on notebooks and laptops, share the same API with Milvus, and integrate with every popular GenAI framework. This webinar is perfect for developers seeking easy-to-use, well-integrated vector databases for their GenAI apps.
Building RAG with self-deployed Milvus vector database and Snowpark Container...Zilliz
This talk will give hands-on advice on building RAG applications with an open-source Milvus database deployed as a docker container. We will also introduce the integration of Milvus with Snowpark Container Services.
Generative AI Deep Dive: Advancing from Proof of Concept to ProductionAggregage
Join Maher Hanafi, VP of Engineering at Betterworks, in this new session where he'll share a practical framework to transform Gen AI prototypes into impactful products! He'll delve into the complexities of data collection and management, model selection and optimization, and ensuring security, scalability, and responsible use.
“An Outlook of the Ongoing and Future Relationship between Blockchain Technologies and Process-aware Information Systems.” Invited talk at the joint workshop on Blockchain for Information Systems (BC4IS) and Blockchain for Trusted Data Sharing (B4TDS), co-located with with the 36th International Conference on Advanced Information Systems Engineering (CAiSE), 3 June 2024, Limassol, Cyprus.
Threats to mobile devices are more prevalent and increasing in scope and complexity. Users of mobile devices desire to take full advantage of the features
available on those devices, but many of the features provide convenience and capability but sacrifice security. This best practices guide outlines steps the users can take to better protect personal devices and information.
A tale of scale & speed: How the US Navy is enabling software delivery from l...sonjaschweigert1
Rapid and secure feature delivery is a goal across every application team and every branch of the DoD. The Navy’s DevSecOps platform, Party Barge, has achieved:
- Reduction in onboarding time from 5 weeks to 1 day
- Improved developer experience and productivity through actionable findings and reduction of false positives
- Maintenance of superior security standards and inherent policy enforcement with Authorization to Operate (ATO)
Development teams can ship efficiently and ensure applications are cyber ready for Navy Authorizing Officials (AOs). In this webinar, Sigma Defense and Anchore will give attendees a look behind the scenes and demo secure pipeline automation and security artifacts that speed up application ATO and time to production.
We will cover:
- How to remove silos in DevSecOps
- How to build efficient development pipeline roles and component templates
- How to deliver security artifacts that matter for ATO’s (SBOMs, vulnerability reports, and policy evidence)
- How to streamline operations with automated policy checks on container images
Encryption in Microsoft 365 - ExpertsLive Netherlands 2024Albert Hoitingh
In this session I delve into the encryption technology used in Microsoft 365 and Microsoft Purview. Including the concepts of Customer Key and Double Key Encryption.
Essentials of Automations: The Art of Triggers and Actions in FMESafe Software
In this second installment of our Essentials of Automations webinar series, we’ll explore the landscape of triggers and actions, guiding you through the nuances of authoring and adapting workspaces for seamless automations. Gain an understanding of the full spectrum of triggers and actions available in FME, empowering you to enhance your workspaces for efficient automation.
We’ll kick things off by showcasing the most commonly used event-based triggers, introducing you to various automation workflows like manual triggers, schedules, directory watchers, and more. Plus, see how these elements play out in real scenarios.
Whether you’re tweaking your current setup or building from the ground up, this session will arm you with the tools and insights needed to transform your FME usage into a powerhouse of productivity. Join us to discover effective strategies that simplify complex processes, enhancing your productivity and transforming your data management practices with FME. Let’s turn complexity into clarity and make your workspaces work wonders!
Essentials of Automations: The Art of Triggers and Actions in FME
Single multifunctional organocatalyst
1. Using a single multifunctional organocatalyst
in a single-step construction of
bispirooxindoles with 3 quaternary stereocentres
LY-NGUYEN Hai Du - 31/10
Tan, B., Candeias, N. R, & Barbas, C. F. Nat. Chem. 2011, 3, 473
2. BISPIROOXINDOLES, WHY?
Spirocyclicooxindole scaffold
F
Cl
H H
N H N
OH N
HN
NH
NHMe NO2 H H
N O
O O OMeN N
N Cl
N MeO N HO H
H H
O O
O
Strychnofoline NITD609
Citrinadin B Cyclopiamine B
Sructural features: > = 1 C */ enantiomerically pure backbone => efficient asymmetric synthetic methods
IN REALITY???
Few transformations meet this requirement
Ar
Cycloaddition processes O O
P R4
OH
R2 O
NH
Ar
R2 CO2R6
R5
Ar = -Naphthyl R5
R4 CHO R1 O R1 O
H2N CO2R6 CH2Cl2 ,RT, N
N
R3 R3
Up to 98% ee
Intramolecular Heck reactions
CO2Me Cyclohexen CO2Me
Pd(OAc)2, (R ) - BINAP
I Ag2CO3, NMP,600C
H
About 46% ee
3.
4. Inherent benefits of using organic molecules as catalysts ?
- available from bio-matter
- intensitive to moisture and air
- non-toxic
- inexpensive and operationally easy to handle
- rich ???
Generic mode of activation commonly used in organocatalysis
Iminium catalysis Enamine catalysis
O N+ N+ more electrophilic O N
NH
H H H H
R' - H2O R' R' - H2O R'
R R R R
more acidic more nucleophilic
more electrophilic
H-bonding catalysis
S
S
X N N
NH NH
H H
R R' X
X= O,NR
R,R',R''= alkyl, aryl R R'
more electrophilic
5. Inherent benefits of using organic molecules as catalysts ?
- available from bio-matter
- intensitive to moisture and air
- non-toxic
- inexpensive and operationally easy to handle
- rich ???
Generic mode of activation commonly used in organocatalysis
Iminium catalysis Enamine catalysis
O N+ N+ more electrophilic O N
NH
H H H H
R' - H2O R' R' - H2O R'
R R R R
more acidic more nucleophilic
more electrophilic
H-bonding catalysis
S
S
X N N
NH NH
H H
R R' X
X= O,NR
R,R',R''= alkyl, aryl R R'
more electrophilic
6. Cinchona alkaloid derivatives activate
electrophile
OMe OMe
6' 6'
OH OH
4' N N 4'
9 8 8 9
N H H N
Quinidine Quinie
activate activate
nucleophile electrophile
activate
electrophile
OH OH OH OH
6' 6' 6' 6'
OR OR O NH2
4' N N 4' 4' N 4' N
9 8 8 9 9 9 8
8
N H H N N N H
QD-1 Q-1 activate QD-3
activate QD-2 nucleophile
nucleophile
Deng et al., 2004
Addition 1,4 of malonates to nitroolefins COOMe COOMe
NO2 QD-1/Q-1(10mol%) 97-99% yield,
R COOMe COOMe NO2 93-96% ee
0
THF,-20 C,36h R
R=aryl, heteroaryl
O O OH O
Baylis-Hilman reaction QD-2
R1 H R2 R1 R2
Guofu Zhong et al. , 2008
R1 O O
O O
Michael-Henry reaction QD-3 O R1
NO2 R 85% =94% yield
O R up to 99 .99% ee
NO2 up to 99:1 dr
O OH
7.
8. 3-substituted oxindoles - efficient Michael donors F3C
Maruoka et al, 2009
O Catalyst CF3
Br
Bu
O P
Catalyst (1-3mol %)
Toluen Bu
O O
Potassium benzoate
N 2-18h,-60-00 C
N CF3
Boc Boc
>96% yield, 90-99%ee F3C
Barbas et al, 2009 R1 Catalyst
S
R R NO2
Ar
NH NH
Catalyst (10 mol %)
NO2 O N
O R1 Ar (CH2)3 (CH2)3 Ar CF3
CHCl3, 24h, -200 C
N N
Ar=
Boc Boc
R=alkyl R1=aryl, heteroaryl >90%yield, >90% ee CF3
Methyleneidolinones - highly reactive Michael acceptors
Chung Chen et al, 2009
Catalyst
ROOC
CHO
R2 OHC R2 Ph
Catalyst (20 mol %)
BA(20 mol %) Ph
OH
DCE,rt to 350C R3 COOR NH OTMS
R1 R1
CHO O
O R3 O
NPG NPG
9. Cinchona alkaloid derivatives used in this study
R4 I :R1= Me, R2=OH, R3=H, R4=CH2=CH Quinine
II :R1= Me, R2=H, R3=NH2, R4=CH3CH2 Hydroquinine amine
R3 N III:R1= Ph, R2=H, R3=OH, R4=CH2=CH Deng's catalyst 1
R2 IV:R1= H, R2=OBz,R3=H, R4=CH2=CH Deng's catalyst 2
R1O
N
N
F3C NH NH N N N
F3C NH NH N
N
S S OMe MeO
CF3 CF3
N N N
VI VII
V
R N NH2 N
NH2 N
NH NH NH NH
NH NH
S OMe S OMe
S OMe
N N
N
X VIII:R=NH2, IX:R=OH XI
R-Diamine S-Diamine
10. Entry Cat. SM2 Solvent Yield(%) d.r e.r
1 I 2a DCM 78 91:9 40:60
2 II 2a DCM 65 80:20 70:30
3 III 2a DCM 83 83:17 58:42
4 IV 2a DCM 67 64:36 51:49
5 V 2a DCM 84 92:8 12:88
6 VI 2a DCM 81 80:20 90:10
7 VI 2a DCE 81 82:18 91:9
8 VI 2a C6H5CN 83 93:7 79:21
9 VI 2a C 6H6 86 92:8 92:8
10§ VI 2a C 6H6 78 88:12 91:9
11 VII 2a DCM 93 >99:1 50:50
12 VIII 2a DCM 86 91:9 95:5
13 IX 2a DCM 74 90:10 86:14
14 X 2a DCM 85 91:9 90:10
15 VIII 2a C 6H6 79 89:11 93:7
16 VIII 2a MeOH 90 94:6 52:48
17 VIII 2a DCE 86 90:10 95:5
18|| VIII 2a DCM 71 88:12 91:9
19 VIII 2b DCM 86 96:4 97:3
20¶ VIII 2b DCM 87 96:4 97:3
Unless otherwise specified:
1a (0.05mol,1.0 equiv.) + 2a/2b (0.075 mol,1.5 equiv.) with 20 mol % catalyst, at room temperature (22 0C)
§ 00C, 36h ; || -150C, 48h; ¶ 15 mol% catalyst
11. Optimization of organocatalytic domino Michael-Aldol reaction
Analysis
Entry 1-18: Michael acceptor 2a (R=-COOMe)
Entry 1: good yield, good diastereoselectivity (d.s), moderate enantioselectivity (e.s)
-> continue examine these conditions : solvent, t0 , ratio of catalyst (20 mol %)
Entry 5,6: higher d.s and e.s ->important role of tertiary amine and thiourea group
( but entry 5 : lower e.s in relation to entry 6 -> use catalyst VI )
Entry 7-10 : slight improvements accompanied changes in solvents + decrease t0
Entry 11: complete d.s >< totally non e.s
Entry 12: trifunctional S – binaphthyl diamine (primary amine) (catalyst VIII)- > excellent result
Entry 13: trifunctional S – binaphthyl diamine (hydroxy group) -> negatve affects
Entry 14: trifunctional R – binaphthyl diamine (primary amine) -> negative affects
Entry 15-17: no significant improvements accompanied changes in solvents
Entry 18: slight drop of d.s and e.s if t0 decreased
Entry 19,20 : Michael acceptor 2b (R= -COPh)
same excellent result, ratio of used catalyst in entry 20 (15 mol%) is lower - > economy
12. Entry R1 R2 R3 Yield (%) d.r e.r
1 Ph Ph H 3b, 84 96:4 97:3
2 Ph Ph 5-F 3c, 92 97:3 97:3
3 Ph Ph 5-Br 3d, 87 95:5 97:3
4 Ph 4-Cl- Ph H 3e, 89 96:4 97:3
5 4-F- Ph Ph H 3f, 81 98:2 95:5
6 3-OMe- Ph Ph H 3g, 79 95:5 98:2
7 2-Furanyl Ph H 3h, 94 >99:1 97:3
8 2-Thiophenyl Ph H 3i, 89 96:4 98:2
9 2-Thiophenyl 4-Cl- Ph H 3j, 88 >99:1 98:2
10 2-Thiophenyl Ph 5-F 3k, 92 >99:1 98:2
11§ Ph 2-Me- Ph H 3l, 69 95:5 91:9
12|| Me Ph H 3m, 56 63:37 97:3
Unless otherwise specified:
1a (0.05mol,1.0 equiv.) + 2a/2b (0.075 mol,1.5 equiv.) with 15 mol % catalyst, at room temperature (22 0C)
§ 48h ; || 12h, pure major diastereomer separated by Chomatography in 56 % yield.
13. Entry R1 R2 R3 R4 Yield (%) d.r e.r
1 Ph H H Me 3a, 78 91:9 95:5
2 3-OMe- Ph H H Me 3n, 79 91:9 95:5
3 2-Furanyl H H Me 3o, 86 93:7 96:4
4 Ph H 6-Cl Me 3p, 74 89:11 94:6
5 Ph 5-MeO H Me 3q, 77 88:12 96:4
6 Ph H H Et 3r, 81 89:11 95:5
14.
15. Investigation of a different protecting group and deprotection of Bispirooxindoles
NH2 N
NH NH
S OMe
Me NAc
PhOC N O
O
(S) OH
15 mol% VIII (S)
83% yield
PhOC Ph 95:5 d.r
(S) (S) 95:5 e.r
O O DCM, rt, 24h
NPG NAc O
NPG
PG=4-Br-Bz
4 2b 5
NAc NH
O O
(S) OH (S) OH
(S)
(S)
Ph HCl (conc.) PhOC Ph
PhOC (R) (S)
(R) (S)
EtOH,800C,2h
O O
NBn NBn
3b (97:3 e.r) 6 (97:3 e.r)
16. Proposed activation mode of catalyst and substrates
S
CHIRAL R'
SCAFFOLD R''
N N N
Ph
H H BnN H
O
II
O I O O
H
N O N
H
R
Control experiment for mechanistic studies
Ph NAc
O Ph O
(S) OH
15 mol% catalyst VIII (S)
Ph Ph
(R) (S)
O O DCM, rt, 24h
NBn NAc O
NBn
PG=4-Br-Bz
4 2b 5
No reaction at all (no hydrogen bond acceptor part like ester or ketone)
17. Conclusion and desire of the group:
- Novel highly efficient organocatalytic construction of bispirooxindoles :
+ direct
+ using simple starting materials
+ mild conditions
+ excellent stereocontrol
+ posibility of access to the opposite enantiomer
- Ambition in future
+ expasion of applcication of the new catalyst in other assymetric transformations
+ investagation of biological activity of compound synthesized
- > hopefully novel lead and therapeutic agents