Options: Natural Products Flashcards by David B

What are features of primary metabolic processes?

Processes esssential to life
They are conserved across species

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What are some examples of primary metabolic processes?

Formation of: carbohydrates, acetly coenzyme A, amino acids, nucleotides, etc

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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

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What is acetyl coenzyme A and mevalonic produced from?

Derived from acetate

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What can acetyl coenzyme A be used to make?

2ndary metabolism process:
Fatty acids
Prostaglandins
Polyketides
Phenols

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What can be made from mevalonic acid?

2ndary metabolism process:
Terpenes
Steroids

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What can amino acids be used for in 2ndary metabolism?

Producing alkaloids

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Define enzymes

Biological catalysts (not used up)
Dictates substrate selectivity, chemio, regio and stereoselectivity of the reaction

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Define cofactors

Biochemical reagents which contain reactive functional group and groups for recognition/binding to the enzyme

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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

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What is NADPH?

Hydride donor

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What is NAD⁺?

Hydride acceptor (deprotonated form of NADH)

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How is NADH synthesised?

Hantsch pyridine synthesis

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What is the mechanism of Hantzsch pyridine synthesis?

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What occurs to Fe(II) and O₂?

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How does Fe(II) and O₂ react with an alkene (and benzene)?

Epoxidation

Benzene - acid to rearomatise to phenol, and can do twice

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How is Fe(II) and O₂ used for benzylic oxidation?

Occurs as activated C-H
Reaction stops here - with KMnO₄ would carry on

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What is SAM, s-adenosyl methionine?

Methylating agent equivalent to MeI

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How is SAM made?

Methionine and ATP -> SAM + triphosphate + nucleoside

S attacks C on ATP via an Sn2 style
Then reacts via Sn2

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How can you alkylate an alcohol biochemically?

ATP then Nucleophillic C or S

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How can you perform acylation biochemically?

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What is the stability of esters and thioesters?

Esters favoured thermodynamically

As S 3p has poorer overlap

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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

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How are polyketides formed?

Enolate chemistry which occurs as produces more stable anion

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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?

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