Flashcards in this deck (182)

• What is the main focus of the Drug Synthesis Lecture 3?

  Major organic reactions and synthetic methodologies.
  pharmacy synthesis
• Who is the lecturer for the Drug Synthesis Lecture 3?

  Dr. M Casely-Hayford.
  pharmacy lecturer
• What is a key concept in drug synthesis regarding molecular shapes?

  Chirality in pharmaceuticals.
  pharmacy chirality
• What role do lead compounds play in drug synthesis?

  They influence the activity of the final drug.
  pharmacy lead_compounds
• Name a common reaction type used in drug synthesis.

  Coupling reactions.
  pharmacy reactions
• What is important about functional groups in drug activity?

  They determine the pharmacological effects.
  pharmacy functional_groups
• How are organometallic reagents utilized in synthesis?

  They aid in forming carbon-carbon bonds.
  pharmacy organometallics
• Identify a drug synthesized involving 3D molecular modeling.

  Aspirin
  drugs molecular_modeling
• What is the significance of Taxol® in pharmaceuticals?

  It's an important chemotherapeutic agent .
  drugs chemotherapy
• What is the significance of understanding carbon reactivity?

  It helps predict how carbon-based compounds will behave in reactions.
  chemistry reactivity
• How do functional groups affect carbon reactivity?

  They influence the chemical properties and reactivity of organic molecules.
  chemistry functional_groups
• What is the Wittig reaction used for?

  It is utilized for synthesizing alkenes from aldehydes or ketones.
  chemistry wittig_reaction
• Define the roles of electrophiles and nucleophiles.

  Electrophiles accept electrons, while nucleophiles donate electrons.
  chemistry electrophiles nucleophiles
• What is meant by functional group synthesis?

  It refers to the creation and transformation of chemical functional groups.
  chemistry functional_group_synthesis
• Identify an essential objective of the study of major organic reactions.

  To master synthetic methodologies and their applications in drug synthesis.
  chemistry organic_reactions drug_synthesis
• What crucial role does medicinal chemistry play?

  It is essential in key stages of developing new pharmaceuticals.
  pharmacy medicinal_chemistry
• Why is a large number of compounds synthesized in drug synthesis?

  To create chemical libraries for screening and identifying lead compounds.
  drug_synthesis pharmaceuticals
• What is a lead compound?

  A chemical compound that shows promise in biological activity for further development.
  pharmaceuticals lead_compound
• List some core concepts in drug synthesis.

  • Overview of drug synthesis importance
  • Role of lead compounds
  • Functional groups in drug activity
  • Chirality in pharmaceuticals
  • Types of coupling reactions
  • Organometallic reagents in synthesis
  drug_synthesis core_concepts
• Why is a lead compound important in drug synthesis?

  It serves as a starting point for further synthesis to identify structure-activity relationships.
  pharmacy drug_synthesis
• What are the goals of further synthesis of lead compounds?

  To achieve optimum desired activity, minimize side effects, and ensure suitable pharmacokinetic properties.
  pharmacy drug_synthesis
• What factors are considered in the optimization of a compound?

  • Desired activity
  • Minimum side effects
  • Suitable pharmacokinetic properties
  pharmacy drug_synthesis optimization
• What may further synthesis aim to identify about drug production?

  The cheapest, safest, and most environmentally friendly method for large-scale production.
  pharmacy drug_synthesis
• What does the synthesis of analogues help in identifying?

  Structure-activity relationships and drug optimization.
  pharmacy drug_synthesis
• What is the first stage in drug development?

  Identification of a drug target
  drug_development stages
• What is developed after identifying a drug target?

  Development of bioassays
  drug_development bioassays
• What is identified after developing bioassays?

  Identification of a lead compound
  drug_development lead_compounds
• What do structure-activity relationships help identify?

  They help identify a pharmacophore
  drug_development pharmacophore
• What is synthesized after identifying lead compounds?

  Synthesis of analogues
  drug_development synthesis
• What are the final stages of drug development?

  Preclinical trials, clinical trials, and process development
  drug_development trials
• What role does drug synthesis play in development?

  It is crucial in multiple key stages
  drug_development synthesis
• What are functional groups?

  They are important to a drug's activity and mechanism of action.
  pharmacy functional_groups
• List some common functional groups in drug structures.

  • Alcohols
  • Phenols
  • Amines
  • Amides
  • Aromatic rings
  pharmacy functional_groups
• What interactions do functional groups have with drug targets?

  Involve intermolecular bonds such as van der Waals, hydrogen, and ionic bonds.
  pharmacy interactions
• How do functional groups affect drugs?

  They determine drug action, stability, and pharmacokinetic properties.
  pharmacy drug_properties
• What bonds are involved in binding interactions between drugs and targets?

  • Van der Waals interactions
  • Hydrogen bonds
  • Ionic bonds
  pharmacy binding_interactions
• What structures and functional groups are shown in the provided image?

  • Amide
  • Pyridine
  • Amine
  • Alcohol
  • Aromatic ring
  • Phenol
  • Alkene
  pharmacy structures image
• What percentage of drugs on the market are chiral?

  About 30%
  pharmaceuticals chirality
• What is a chiral molecule?

  A molecule with two non-superimposable mirror images called enantiomers.
  chemistry chirality
• Why are drug targets typically chiral?

  They can distinguish between two enantiomers, affecting drug activity.
  pharmaceuticals chirality
• What is a known effect of enantiomers in drugs like Thalidomide?

  • One is an active sedative
  • The other is teratogenic
  pharmaceuticals drugs
• What is a racemic mixture?

  A mixture of two enantiomers, such as in propranolol.
  chemistry pharmaceuticals
• What is a challenge in synthesizing chiral drugs?

  The need to selectively synthesize a specific enantiomer.
  chemistry drug_synthesis
• Identify the chiral centers in the following structures: Salbutamol and Indinavir.

  See the image for molecular structures with marked chiral centers.
  chemistry structures
• Which drug has a marked chiral center: Nevirapine or Omeprazole?

  Omeprazole has a marked chiral center.
  pharmaceuticals structures
• What role do functional groups play in drug synthesis?

  They influence drug activity and are crucial for the synthetic process.
  pharmacy synthesis functional_groups
• What is the aim of drug synthesis?

  To create a target molecule (drug) from available building blocks.
  pharmacy synthesis targets
• What is chemo-selectivity in drug synthesis?

  Preferred reactions occurring at one specific functional group.
  pharmacy synthesis chemo-selectivity
• Define regioselectivity in the context of drug synthesis.

  Selectivity of reactions at one of several possible positions on a functional group.
  pharmacy synthesis regioselectivity
• What is a challenge in drug synthesis regarding functional groups?

  Multiple reactive functional groups can complicate the process.
  pharmacy synthesis challenges
• Why is it ideal for reactions in drug synthesis to yield a single product?

  It avoids complications from mixtures and enhances yield precision.
  pharmacy synthesis products
• How do functional groups change during reactions?

  They can be converted to different functional groups as a result of the reaction.
  pharmacy synthesis functional_groups
• What is regioselectivity in organic reactions?

  Regioselectivity occurs when a reaction at a functional group happens at one of several possible positions, e.g. in aromatic rings.
  chemistry regioselectivity
• Why is the reaction to make Salmeterol considered regioselective?

  The amine reacts with the less substituted position of the epoxide.
  chemistry salmeterol
• What does the reaction to synthesize Salmeterol demonstrate about chemo-selectivity?

  The amine reacts with the epoxide, not the methyl ester.
  chemistry chemo-selectivity
• What is the chemical reaction scheme for synthesizing (R)-Salmeterol?

  Reactants include an epoxide and amine, with conditions LiAlH4 and H2/Pd/C.
  chemistry synthesis
• What type of drug is (R)-Salmeterol?

  It is a beta-2 agonist used in asthma treatment.
  pharmacy drugs
• What are coupling reactions mainly used for?

  To link two molecular building blocks to create a larger molecule.
  chemistry reactions
• Which new bonds are formed in coupling reactions?

  • O-C bonds (esters)
  • N-C bonds (amides/amines)
  • C-O-C bonds (ethers)
  chemistry bonds
• What types of bonds do coupling reactions help form?

  • C-C single bonds
  • C=C double bonds
  chemistry bonds
• Name some examples of C-C bond forming reactions.

  • Friedel Crafts alkylation/acylation
  • Wittig reaction
  • Suzuki reaction
  • Sonogashira reaction
  chemistry reactions
• What do Grignard reactions target?

  The carbonyl group of aldehydes and ketones.
  chemistry grignard
• What type of bond is formed when building blocks couple with an amine and a carboxylic acid?

  Amide bond
  chemistry synthesis
• List the groups that can couple to form an amide bond.

  • Amine
  • Carboxylic acid
  • Acid chloride
  • Acid anhydride
  • Ester group
  chemistry functional_groups
• What is an important reaction in drug synthesis?

  Formation of N-C bonds using amide bonds
  chemistry drug_synthesis
• Provide a generalized diagram related to anhydrides.

  
  chemistry structures
• What is the role of amide bonds in drug synthesis?

  They couple building blocks to form complex molecules.
  chemistry synthesis
• What type of bond is formed by coupling building blocks containing an amine and a carboxylic group?

  An amide bond is formed.
  chemistry synthesis
• Which compound is synthesized from 4-aminophenol using acetic anhydride?

  Paracetamol is synthesized.
  chemistry synthesis pharmaceuticals
• What defines a chemoselective reaction?

  A reaction occurs at a specific functional group over others.
  chemistry reactions
• Which functional group is more nucleophilic, amine or phenol?

  Amine nitrogen is more nucleophilic than phenol oxygen.
  chemistry nucleophilicity
• What is represented by this image: ?

  The synthesis of Paracetamol from 4-aminophenol using acetic anhydride via N-C coupling.
  chemistry synthesis visual
• What type of bond is formed during the synthesis of N-acetylprocainamide?

  Amide bond formed by coupling an amine and a carboxylic acid chloride.
  chemistry synthesis bonds
• Which compounds are involved in the synthesis of N-acetylprocainamide?

  • Acid chloride
  • Procainamide (Amine)
  chemistry synthesis compounds
• What is the key reaction in forming N-acetylprocainamide?

  N-C Coupling reaction.
  chemistry synthesis reactions
• Name the product formed from the reaction of procainamide and acid chloride.

  N-Acetylprocainamide.
  chemistry synthesis products
• What is an example of a coupling reaction in drug synthesis?

  Formation of an amide bond in synthesizing N-acetylprocainamide.
  chemistry synthesis coupling
• Provide a visual example of the synthesis of N-acetylprocainamide.

  
  chemistry visual
• What type of bond is formed through N-C coupling?

  An amide bond is formed through N-C coupling.
  organic chemistry bonding
• Why are carboxylic acids unreactive towards amines?

  Carboxylic acids are unreactive towards amines due to the formation of salts.
  organic chemistry amines
• What is a coupling agent used to activate carboxylic acids?

  Diisopropylcarbodiimide (DIC) is a coupling agent used for activation.
  organic chemistry coupling
• What reagent reacts with carboxylic acids to form more reactive mixed anhydrides?

  Ethyl chloroformate reacts with carboxylic acids to form mixed anhydrides.
  organic reagents chemistry
• What is the outcome of using a mixed anhydride in amide formation?

  Mixed anhydrides are more reactive towards amines, facilitating amide formation.
  organic chemistry amide
• What compound is synthesized from carboxylic acid and amine through N-C coupling?

  Nemonapride is synthesized through N-C coupling of carboxylic acid and amine.
  drug synthesis nemonapride
• What factors influence drug synthesis outlined in the notes?

  • Overview of drug synthesis importance
  • Role of lead compounds
  • Functional groups in drug activity
  • Chirality in pharmaceuticals
  • Types of coupling reactions
  • Organometallic reagents in synthesis
  synthesis pharmaceuticals chemistry
• What overall approach is discussed in the document?

  The document outlines approaches to drug synthesis with a focus on major organic reactions and methodologies.
  synthesis overview chemistry
• What visual aids accompany the synthesis process discussed?

  See the following image:
  chemistry visual synthesis
• What type of linkage is formed during N-C coupling?

  An amine linkage is formed.
  chemistry synthesis
• What are the two components needed for an amine bond in N-C coupling?

  An amine and an alkyl halide.
  chemistry synthesis
• What was synthesized by reacting an amine with an alkyl chloride?

  Azaperone was synthesized.
  chemistry drugs
• What is the nature of the reaction between the amine and alkyl halide?

  The reaction is chemoselective.
  chemistry synthesis
• Which component does the amine react with in N-C coupling?

  The amine reacts with alkyl halide rather than the ketone.
  chemistry reactions
• What does the provided chemical reaction image represent?

  It shows the synthesis of Azaperone from Alkyl chloride and Amine via N-C Coupling.
  chemistry synthesis
• What is the product formed from the reaction of an amine with a ketone under reducing conditions?

  Cyclopentamine
  synthesis organic_chemistry
• What type of linkage is formed in N-C coupling?

  Amine linkage
  synthesis organic_chemistry
• Describe the reaction of amine with ketone in N-C coupling.

  Amine reacts with ketone to form an imine, then reduced to an amine.
  synthesis organic_chemistry
• What is an imine in the context of N-C coupling?

  An intermediate formed from the reaction of amine and ketone.
  synthesis organic_chemistry
• What reducing agent is used in the formation of amine from imine?

  H2 [Raney Ni]
  synthesis organic_chemistry
• What is the first step in forming cyclopentamine from amine and ketone?

  Formation of imine
  synthesis organic_chemistry
• What visual representation illustrates the synthesis of Cyclopentamine?

  
  synthesis organic_chemistry visual
• What is the O-C coupling used for in drug synthesis?

  It is used to form esters and ethers.
  synthesis organic_chemistry
• What components are needed to form esters?

  • Alcohol or phenol
  • Carboxylic acid or derivative (anhydrides, acid chlorides)
  chemistry esters
• Which compound is synthesized from Salicylic acid using acetic anhydride?

  Acetylsalicylic acid (aspirin)
  pharmaceuticals aspirin
• Name a drug synthesized via O-C coupling besides aspirin.

  Hexylcaine
  pharmaceuticals synthesis
• What is Meprylcaine an example of?

  A drug synthesized through O-C coupling.
  pharmaceuticals synthesis
• What do anhydrides and acid chlorides have in common?

  They are both carboxylic acid derivatives used in forming esters.
  chemistry derivatives
• How is O-C coupling relevant to pharmaceuticals?

  It's a method for synthesizing important drug compounds.
  synthesis pharmaceuticals
• Provide an example of O-C coupling reaction pathway.

  Hexylcaine and Meprylcaine synthesis.
  synthesis pathways
• What is depicted in the provided chemical reaction image?

  Synthesis of Acetylsalicylic acid (aspirin) via O-C coupling.
  chemistry reaction
• What is phenol used in the synthesis of?

  Esters through O-C coupling.
  synthesis phenol
• What is formed when an alcohol reacts with an alkyl halide?

  An ether linkage is formed.
  chemistry organic
• What is the synthesis method for the anticancer agent etoglucid?

  It is synthesized by reacting a diol with two equivalents of alkyl chloride.
  chemistry drugs
• What reagents are used in the O-C coupling for ether formation?

  BF3 and KOH are used as reaction reagents.
  chemistry reagents
• Identify the product of the O-C coupling reaction shown.

  The product is Etoglucid.
  chemistry products
• What type of bond is formed during the coupling of O-C?

  An ether bond is formed.
  chemistry bonds
• What is the overall reaction scheme for the synthesis of Etoglucid?

  Alcohol + Alkyl Chloride → Ether (Etoglucid).
  chemistry reaction
• What does the reaction scheme for Etoglucid include?

  It includes Alcohol, Alkyl chloride, O-C Coupling, and Ether.
  chemistry synthesis
• How do ethers form through alcohol and alkyl halide reactions?

  By undergoing an O-C coupling reaction.
  chemistry organic
• What is the art of making nature's molecules and current drugs called?

  Organic (drug) synthesis
  synthesis pharmacy
• Why is organic synthesis important for drug development?

  Due to inadequate supply from natural sources of ligands with biological activity.
  drug_development importance
• What can organic (drug) synthesis help design?

  Analogues with better safety profiles.
  safety design
• Why is the synthesis of new organic molecules commercially vital?

  Pharmaceutical companies strive to create new chemical entities (NCEs).
  commercial pharmaceuticals
• What is a significant challenge with natural products?

  They often have toxic side effects.
  toxicity natural_products
• What is one key aspect of drug synthesis outlined in the core concepts?

  The role of lead compounds.
  lead_compounds synthesis
• What functional aspect of drugs is important in synthesis?

  Chirality in pharmaceuticals.
  chirality pharmaceuticals
• Which type of reactions are essential in organic drug synthesis?

  Types of coupling reactions.
  coupling_reactions reactions
• What reagents are significant in organic synthesis?

  Organometallic reagents.
  organometallic synthesis
• What types of bonds are present in Taxol?

  • C=C
  • C-C
  • C-N
  • C-O
  • C=O
  • O-H
  • N-H
  • OH
  chemistry pharmaceuticals bonds
• What is the significance of bonds in drug synthesis?

  Bonds determine the structure, stability, and activity of the drug.
  chemistry drug_synthesis
• Describe one of the methods used to create bonds in Taxol.

  Synthesis involves using coupling reactions with organometallic reagents.
  chemistry synthesis
• How do functional groups affect drug activity?

  Functional groups influence drug solubility and binding to biological targets.
  chemistry functional_groups
• What role does chirality play in pharmaceuticals?

  Chirality affects the interaction of drugs with biological systems, impacting efficacy.
  chemistry chirality pharmaceuticals
• What is an example of a bond in Taxol and its significance?

  The C=O bond plays a crucial role in the drug's mechanism of action.
  chemistry bonds
• List two types of bonds present in Taxol.

  • C-O
  • O-H
  chemistry bonds
• What is the visual representation of Taxol?
  chemistry visual
• Why are functional groups needed in bond formation?

  To aid in the formation of chemical bonds.
  chemistry functional_groups
• What does bond polarization indicate?

  It provides insights into the formation of the carbon framework.
  chemistry bond_polarization
• What type of reaction involves an electrophile and a nucleophile?

  They react with each other in various synthetic processes.
  chemistry electrophile_nucleophile
• What are the major focuses of drug synthesis?

  • Importance of drug synthesis
  • Role of lead compounds
  • Functional groups in drug activity
  • Chirality in pharmaceuticals
  • Types of coupling reactions
  • Organometallic reagents in synthesis
  chemistry drug_synthesis core_concepts
• What do functional groups on a molecule affect?

  Polarisation and reactivity of the molecule.
  chemistry functional_groups
• What do Electron Withdrawing Groups (EWGs) do to carbon atoms?

  Confer partial positive charges on carbon atoms.
  chemistry ewgs
• What is an electrophile?

  An electron-loving species with a positively polarized atom.
  chemistry electrophiles
• How does an electrophile react with a nucleophile?

  It can form a bond by accepting a pair of electrons.
  chemistry reaction_mechanisms
• Identify the structure of an epoxide with partial charges.

  
  chemistry epoxides
• Identify the structure of a ketone with partial charges.

  
  chemistry ketones
• Identify the structure of an alkyl halide with partial charges.

  
  chemistry alkyl_halides
• What type of molecules are epoxides?

  Useful electrophiles
  chemistry electrophiles
• Why is the C—O bond in epoxides polarized?

  Oxygen is more electronegative than carbon.
  chemistry polarization
• What fundamental role does the carbonyl group play in synthesis?

  It is a cornerstone for C-C synthesis.
  chemistry carbonyl
• In what two roles can the carbonyl group act?

  • Nucleophile
  • Electrophile
  chemistry carbonyl
• Where does a nucleophile typically attack in a carbonyl group?

  On the trigonal planar sp2 hybridized carbon.
  chemistry carbonyl
• What do carbon nucleophiles react with?

  Electrophiles to form new C—C bonds.
  chemistry nucleophiles
• Name the three categories of carbon nucleophiles.

  • Organometallics
  • Stabilised carbanions
  • Neutral nucleophiles
  chemistry nucleophiles
• What are organometallics?

  Compounds containing a carbon-metal bond.
  chemistry organometallics
• Define stabilised carbanions.

  Anionic species where a carbon atom has a negative charge, stabilized by surrounding groups.
  chemistry carbanions
• What are neutral nucleophiles?

  Activated pi-systems that can react as nucleophiles.
  chemistry nucleophiles
• What are Grignard Reagents used for?

  To form new C—C bonds as carbon nucleophiles.
  chemistry organometallics
• What is the general structure of a Grignard reagent?

  R—MgX
  chemistry structures
• What does the electronegativity chart show?

  The relative electronegativities of elements.
  chemistry periodic_table
• What type of bond is present in CH3-MgX?

  The C—MgX bond is highly polarized.
  chemistry organometallics
• What does CH3-MgX behave as?

  It behaves as a carbanion.
  chemistry organometallics
• How is CH3-MgX formed?

  By the reaction of magnesium metal with an alkyl or aryl halide.
  chemistry reagents
• What is the reaction for forming CH3-MgX?

  CH3-Br + Mg → CH3-MgX.
  chemistry organometallics
• What is the order of reactivity of halides?

  RI > RBr > RCl.
  chemistry reactivity
• What do Grignard reagents react well with?

  They react well with carbonyl electrophiles.
  chemistry organometallic
• What types of compounds do Grignard reagents add to?

  They add to aldehydes and ketones.
  chemistry reactions
• What is a primary use of Grignard reagents?

  They are used to make alcohols.
  chemistry organometallic
• Describe the mechanism of Grignard reagent addition.

  They add a nucleophile to carbonyl carbon, converting it to an alcohol.
  chemistry mechanism
• What is the significance of Grignard reagents in drug synthesis?

  They facilitate the formation of complex organic structures.
  pharmaceutical synthesis
• What can Grignard reagents react with to produce alcohols?

  Epoxides
  chemistry reagents
• What is the structure of a common Grignard reagent?

  CH3CH2MgBr
  chemistry reagents
• What reacts with Grignard reagents to form carboxylic acids?

  Carbon dioxide (CO₂)
  chemistry synthesis
• What is the function of Grignard reagents in synthesis?

  To synthesize carboxylic acids
  chemistry reagents synthesis
• What type of compound is CH3CH2MgBr?

  A Grignard reagent
  chemistry organic_compounds
• What is a key step in the industrial production of Tamoxifen?

  The Grignard reaction.
  chemistry synthesis tamoxifen
• What type of breast cancer does Tamoxifen treat?

  Estrogen receptor positive breast cancer.
  medicine oncology
• What is used in the Grignard reaction for Tamoxifen synthesis?

  An organomagnesium compound like MgBr.
  chemistry grignard synthesis
• Which solvent is commonly used in the Grignard reaction?

  THF (Tetrahydrofuran).
  chemistry solvents synthesis
• What is the reaction for forming organolithium reagents?

  R—X + Li → R—Li + LiCl
  organometallic chemistry synthesis
• How do organolithium reagents behave compared to Grignard reagents?

  They behave similarly but are more reactive.
  organometallic chemistry reagents
• What is the product of nucleophilic addition of an alkyne to a ketone?

  Forms a 3° alcohol.
  organic synthesis ketone
• What is the sequence of reagents in the conversion of Estrone to Ethynylestradiol?

  Add Li, then H+/H2O for C-C Coupling.
  synthesis drugs chemistry