Options: Natural Products Flashcards
What are features of primary metabolic processes?
Processes esssential to life
They are conserved across species
What are some examples of primary metabolic processes?
Formation of: carbohydrates, acetly coenzyme A, amino acids, nucleotides, etc
What is a secondary metabolic process?
Processes non-essential to life
Change species to species
Rel small # of starting materials and wide range of products
What is acetyl coenzyme A and mevalonic produced from?
Derived from acetate
What can acetyl coenzyme A be used to make?
2ndary metabolism process:
Fatty acids
Prostaglandins
Polyketides
Phenols
What can be made from mevalonic acid?
2ndary metabolism process:
Terpenes
Steroids
What can amino acids be used for in 2ndary metabolism?
Producing alkaloids
Define enzymes
Biological catalysts (not used up)
Dictates substrate selectivity, chemio, regio and stereoselectivity of the reaction
Define cofactors
Biochemical reagents which contain reactive functional group and groups for recognition/binding to the enzyme
What are the classes of metabolic enzymes?
Oxidoreductases - redox reactions
Transferases - functional group transfers
Hydrolases - bond hydrolysis
Lyases - elim reactions, and ring formation
Isomerases - isomerisation reactions
Ligases - condensation reactions
What is NADPH?
Hydride donor
What is NAD+?
Hydride acceptor (deprotonated form of NADH)
How is NADH synthesised?
Hantsch pyridine synthesis
What is the mechanism of Hantzsch pyridine synthesis?
What occurs to Fe(II) and O2?
How does Fe(II) and O2 react with an alkene (and benzene)?
Epoxidation
Benzene - acid to rearomatise to phenol, and can do twice
How is Fe(II) and O2 used for benzylic oxidation?
Occurs as activated C-H
Reaction stops here - with KMnO4 would carry on
What is SAM, s-adenosyl methionine?
Methylating agent equivalent to MeI
How is SAM made?
Methionine and ATP -> SAM + triphosphate + nucleoside
S attacks C on ATP via an Sn2 style
Then reacts via Sn2
How can you alkylate an alcohol biochemically?
ATP then Nucleophillic C or S
How can you perform acylation biochemically?
What is the stability of esters and thioesters?
Esters favoured thermodynamically
As S 3p has poorer overlap
What is the pKa of esters compared to esters?
Thioester pKa is around that of anhydride rather than ester
Means enolate chem of thioester closer to ketone
How are polyketides formed?
Enolate chemistry which occurs as produces more stable anion
What are fatty acids?
What is required for fatty acid synthesis?
CO2 required but those C are not incorporated into fatty acids
Malonyl coenzyme A is starting material
How is malonyl coenzyme A made in step 1 of fatty acid synthesis?
Uses biotin - which is a CO2 carrier
What are the steps in fatty acid synthesis?
1) Malonyl coenzyme A synthesised
2) form a β-unsaturated thioester
3) Form an ester
How does a form a β-unsaturated thioester form in fatty acid synthesis?
(step 2)
How does a form fatty acids from β-unsaturated thioesters?
What is the complex in fatty acid synthase?
All enzymes are in the same complex
Also uses acyl carrier proteins - shuttles around complex to enzyme reaction site
How are fatty acids unsaturated or saturated?
Unsaturation by a disulfide
Saturation by O2
What are the uses of prostaglandins and leukotrienes?
Sensing pain
Inflammation
What are prostaglandins made from?
Fatty acids
which themselves are made from acetyl CoA as above
What enzyme is used for prostaglandin synthesis and how is it inhibitied?
Cyclooxygenase (COX) - Fe dependent enzyme
Inhibited by drugs such as ibuprofen, which prevents pain/inflammation
What is arachidonic acid?
Fatty acid commonly used in synthesis of prostaglandin or leukotrienes
How are prostaglandins synthesised from arachidonic acid?
Cyclooxygenase (COX) dependent
First radical is doubly-stabilised as it is a diene
What can be done to modify prostaglandins?
Use different reagents:
NADH cleaves O-O bond in ring to give OH
Selectively reduce terminal peroxide then treat with acid
How are leukotrienes synthesised from arachidonic acid?
5-lipoxygenase enzyme and O2
What are polyketides used for?
Synthesis of polyaromatics
What is an example of mechanism for tetraketides reacting to form an aromatic?
Can have deprotonation at different areas
How can you introduce diversity to ketides?
Branching - Base then SAM for methylation
Decarboxylation after thioester to carboxylic acid
What is a common side-reaction in polyaromat synthesis?
If NADH to produce aldehyde can also have intra attack
How can oxidase be used when making polyaromats?
How can dioxygenase be used in polyaromat synthesis?
When are partially saturated polyketides made?
Made from interrupted sequence during their synthesis
How can you make a partially saturated polyketide?
Where:
KS = ketosynthase - extends by one ketide
KR = ketoreductase - reduces non thio carbonyl
DH = dehydratase - alcohol to alkene
ER = enoyl reductase - enone to carbonyl
What is isoprene?
Thought to be base unit of isoprenoids and terpenes
How can you create an isoprene equivalent?
Acetyl coenzy A -> R-mevalonic acid -> isoprene equivalent
What is R-mevalonic acid?
This is intermediate to producing an isoprene equivalent
How do you synthesise mevalonic acid from acetyl coenzyme?
1)Acetyl CoA + 2x Acetacetyl CoA then hydrolysis
2)Reduction with NADH and H+
How is mevalonic acid reacted to make an isoprene equivalent?
React OH with 2xATP (primary then teriary)
How does isopentyl pyrophosphate react in acid?
This generally occurs before reacts in biological synthesis
What is the reactivity of isopentyl pyrophosphate with nuc?
How are terpenes made from isopentyl pyrophosphate?
This can go on to produce longer terpenes (all E)
Then will intramolec react
How are terpenes form from intermediate?
Intramolec reaction
How are bridged cyclic systems made from terpenes?
How does the wagner-meerwein shift occur in terpene shift to give diversity?
Always look at putting the +ve charge on more sub atom
How can terpenes be modified with COX?
Replaces an alkyl H with OH
Can then be oxygenated via NAD+ to carbonyl
What is squalene?
Intermediate in cholesterol synthesis
How is squalene synthesised?
Produce 2x farnesyl pyrophosphate which can then couple with eachother
How do 2x farnesyl pyrophosphates couple?
How does squalene convert to make a steroid?
Use COX to form epoxide then draw chairs (next to eachother) and do a chain alkene process
Then use Enz to abstract protn and sequential 1,2- C-H/C-Me migrations
What does a desaturase enzyme do?
Forms an alkene from alkyl in a cholesterol molecule
Abstracts H2
What does vitamin D mean?
Group of structurally related secosteroids
They regulate absorption of minerals such as Ca2+ and Mg2+
How can you make a vitamin D compound?
UV (like sunlight on skin!)
Causes 6π photochem electrocyclic ring opening
What are alkaloids?
N-containing 2° metabolite (non-peptidic/nucleoside)
Mostly derived from α-amino acids
Types: aliphatic, aromatic, indole alkaloids
What are examples of aliphatic alkaloids?
How are amino acids biosynthesised conceptually?
α-ketocarboxylate to α-amino acid
Amine transfer using pyridoxamine / pyridoxal phosphate
Uses: aminotransferase, glutamic acid
What is the mechanism for amino acid synthesis?
This is in wrong order
How can you use pyridoxal phosphate to racemise an amino acid?
How is pyridoxal phosphate used as a cofactor?
Acts as an aldehyde
N can attack to form an imine
Then reacts via imine chemistry
What reactions use pyridoxal phosphate as a cofactor?
- C-C formation
- Sub at β-position at α- amino acids
- Internal redox reactions
- Oxn of primary amine
How do you perform a decarboxylation of an amino acid?
How is proline synthesised?
How is orthinine synthesised from glutamate?
What is the urea cycle?
How is α-ketoglutarate?
How is lysine synthesised?
What is the overview of glycolysis?
Glucose to pyruvate
Produces ATP, CO2, and H2
What occurs in glycolysis?
What is thiamine pyrophosphate (TPP)?
Acts like a cyanide:
Good nuc
Stabilises adj -ve charge
Good LG
How can you use TPP for a reaction?
What is the mech of using TPP?
How does an amide with an aromatic system react with POCl3?
How can an aryl group react with an imine?
What technique can be used to make complex alkaloids?
Oxidative radical coupling
Includes ortho/para or ortho/ortho coupling
What is the mechanism of oxidative radical coupling when ortho/para?
What is the mechanism of oxidative radical coupling when ortho/ortho?
What does this reagent do?
Reacts with more e- rich OH (out of the ones on the ring)
Gives RO-I(Ph)-OCOCF3
What is the polonovski reaction?
