Biosynthesis Flashcards

1
Q

What is nature’s enol equivalent?

What is its reactivity like?

A

Nature uses acetyl co-enzyme A as its enol. The ketone in the actyl group can tautomerise to an enol.

Acetyl CoA has the same reactivity as a thioester in the lab - the equilibrium is 50:50 between the keto and enol form.

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2
Q

What reaction can acetyl CoA alone undergo in nature?

Draw the mechanism.

A

Acetyl CoA undergoes Claisen reactions in nature, where the keto and enol forms react to make acetoacetyl CoA.

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3
Q

How does nature run reductive amination?

A

In nature, two cofactors and an aminotransferase enzyme are used for reductive amination.

The two cofactors are called pyridoxamine and pyridoxal.

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4
Q

What are two common reactions that the two cofactors are used for?

A
  • reversible synthesis of amino acids from keto acids via amination/deamination
  • decarboxylation of amino acids to give amines
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5
Q

Draw the mechanism for the reversible synthesis of amino acids from keto acids.

A
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6
Q

How does nature’s methylation occur?

Draw the mechanism(s).

A

Nature’s methylation uses s-adensoyl methionine (SAM).

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7
Q

What are the three classes of natural products?

A
  1. Alkaloids
  2. Polyketides
  3. Terpenes
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8
Q

Where do alkaloids come from?

A

Most alkaloids come from an amino acid biosynthetic precursor. The most common amino acids used are ornithine, lysine, tryptophan, phenylalanine and tyrosine.

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9
Q

What are the important reactions in the biosynthesis of alkaloids?

A
  1. Decarboxylation
  2. Deamination of amino acids then decarboxylation
  3. Imine/iminium ion formation
  4. Mannich reaction
  5. Methylation
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10
Q

Draw curly arrows to demonstrate what the Mannich reaction is.

A
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11
Q

What are pyrrolidine alkaloids synthesised from?

Give an example of a pyrrolidine alkaloid.

A

Pyrrolidine alkaloids include a 5-membered N-containing ring. Most of these are from ornithine as a biosynthetic precursor. An example is hygrine.

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12
Q

Draw the mechanism for hygrine synthesis.

A
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13
Q

Draw the mechanism for the synthesis of tropinone from hygrine.

A
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14
Q

Where do piperidine alkaloids come from?

Give an example and draw its structure.

A

Most 6-membered rings in piperidine alkaloids come from lysine. One example is pseudopelletierine.

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15
Q

Draw the mechanism for the biosynthesis of pseudopelletierine

A

*here, only one amine is methylated. This shows how nature can be both regio- and stereoselective.

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16
Q

Where do isoquinoline alkaloids come from?

Give and example and draw its structure.

A

Isoquinoline alkaloids usually come from tyrosine, such as salsolinol.

17
Q

Draw the mechanism for the biosynthesis of salsolinol.

A

The acetyl carbonyl used to form the iminium ion comes from alanine.

18
Q

Where do benzoisoquinoline alkloids come from?

Give an example and draw its structure.

A

Benzoisoquinoline alkaloids usually come from tyrosine, such as reticuline.

19
Q

Draw the mechanism for the biosynthesis of reticuline.

A
20
Q

Where do polyketides come from?

A

Polyketides are formed from malonyl CoA, which in turn forms from acetyl CoA.

21
Q

What is the key structural feature of a polyketide?

A

A polyketide has many ketone groups, with each C=O being separated by a CH2 group.

22
Q

Draw the mechanism for the biosynthesis of malonyl CoA.

A
23
Q

How are polyketides constructed?

Draw the mechanism and its short hand version.

A

Polyketides are synthesised by a multienzyme complex containing a condensing enzyme (CE) and an acyl carrier protein (ACP).

24
Q

How are aromatic polyketides numbered?

What are the structural features of aromatic polyketides?

A

You give an OH group 1 then number around the ring.

Polyketides show multiple oxygenation groups (OH or C=O) around an aromatic ring, either in a 1,3- or a 1,3,5-pattern.

25
Q

Draw the mechanism for the biosynthesis of orsellinic acid.

A

In the last step, the keto to enol tautomerisationis driven by the generation of full aromaticity. Usually the keto form is preferred but here it’s not.

26
Q

Where do terpenes come from?

A

Terpenes are synthesised from mevalonic acid, which in turn comes from acetyl CoA.

27
Q

What is the structural feature of terpenes?

A

The structure of terpenes is always a multiple of 5 carbons, with 10 carbons being the smallest (monoterpene).

28
Q

Draw the mechanism for the synthesis of mevalonic acid.

A
29
Q

What happens to mevalonic acid before it can go on to synthesis terpenes?

A

Nature’s leaving group, OPP, is attached to mevalonic acid. Then, mevalonic acid produces two different pyrophosphate isomers.

30
Q

Draw the mechansim for the synthesis of limonene.

A

GPP is synthesised, which is the C10 terpene building block.

31
Q

Draw the two kinds of Wagner-Meerwein hydride shifts.

A
32
Q

Draw one kind of Wagner-Meerwein alkyl shift.

A
33
Q

What is the C15 terpene building block?

Draw its synthesis.

A

FPP is the C15 terpene synthesis.

34
Q

Draw curly arrows to show the conversion between cis- and trans-FPP.

A
35
Q

Draw two different ways FPP can form C15 terpene molecules.

A