Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Core 5 > Synthesis of biological molecules > Flashcards

Synthesis of biological molecules Flashcards

1
Q

Why are synthetic peptides and carbohydrates important?

A

Therapeutics:

drugs, vaccines, targetted drug delivery

Prove the structure of a natural product

Study of biological processes:

  • ligand receptor interactions
  • enzyme subrate interactions

enzyme reaction mechanisms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are carbohydtrates used for?

A

cell recognition and adhesion

cell signalling

binding of pathogens

physical barriers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the structure of amino acids?

A

N terminus ion the left

C terminus on the right

Amino acids have three letter or one letter codes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How many amino acids constitute different titles of protein?

A

Peptide < 50 amino acids

Protein > 50 amino acids

Di peptide 2 amino acids

Oligopeptide 2-15 amino acids

Poly peptide 15-50 amino acids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What forms can a carbohydtrate exist in?

A

Open chain (acyclic)

Fischer form - the chain is bent round to look cyclic but is not bonded together

Chair form - anomeric hydroxyl is placed axial or equatorial

Axial = alpha

equatorial = beta

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are 3 examples of carbohydrates?

A

galactose, N-acetylgluosamine (GlcNac) and mannose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How is a glycosidic bond formed?

A

Formed in a condensation reaction between two hydroxyl groups on two separate sugars

Gal - α1, 6 - GlcNac = glycosidic bond between C1 on Gal and C6 on GlcNac

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How do we achieve efficient and selective coupling of two amino acids?

A

Activate the C terminal carboxylic acid by turning the OH to a better leaving group

Avoid self-coupling by installing protecting groups

Avoid reaction with other functional groups by installing protecting groups

Use enantimeroically pure amino acids - want the S form

Avoid racemisation / lossof stereochemistry

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How are amino acids activated in nature?

A

Activated through coupling to tRNA

Ribosome catalyses peptide nbond formation

Hydrogen bonding networks and orecise positioning of substrates promote reaction between the correct groups

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How can we react amino acids synthetically?

A

Convert the hydroxyl of the carboxylic acid to an acyl chloride with COCl3 in DMF

Chlorine is a better leaving group than OH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the major problem with synthetic di peptide formation?

A

Side reactions:

Resonance delocalises the lone pair on N onto O

O- then reacts with acyl chlorideto form oxazolone

Oxazolone can tautomerise twice with a base

During tautomerisation the H can add from the top or bottom of the molecule - leads of loss of stereochemistry

Oxazolone can still react with the second amino acid which forms a mixture of products

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How can we activate the hydroxyl?

A

DCC with a mild base that cannot act as a nucleophile - ensures the NH2 is not protonated

There is no internal cyclisation

The biproduct precipitates out of solution - easy to separate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What arethe most common protecting groups for the N terminus and C terminus?

A

N: Boc and F moc

C: methyl ester, t-butyl ester, benzyl ester,

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the mechanism and conditions for installation and removal of Boc?

A

Installation: t-butyloxycarbonyl

Removal: TFA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the mechanism and conditions for installation and removal of Fmoc?

A

Installation: Fmoc-Cl and NaHCO3

Removal: piperidine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the mechanism and conditions for installation and removal of a methyl ester?

A

Installation: MeOH / H+ (HCL)

Removal: NaOH / H+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the mechanism and conditions for installation and removal of a t-Butyl ester?

A

Installation: 2-methyl propene / H+

Removal: TFA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the mechanism and conditions for installation and removal of a benzyl ester?

A

Installation: benzyl alcohol and H+

Removal: hydrogenatio: H2 / Pd/C catalyst

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How can we protect side chains?

A

Carboxylic acids (aspartic, glutamic acid) - methyl esters, butyl esters, benzyl esters

amines (lysine): Boc and Cbz

Hydroxyl (serine, threonine, tyrosine) -

tert butyl ether

benzyl ether

silyl ether (TBDMS)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How do we instal and remove Cbz?

A

Installation: benzyloxycarbonyl (Cbz) + NaHCO3

Removal - H2 / Pd/C

Forms a carbamate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How do we instal and remove tert butyl and bezyl ethers?

A

Installation: Benzyl / tert butyl bromide + base

Removal catalytic hydrogenation - H2 / Pd/C

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How do we instal and remove silyl ethers

A

Installation: silyl ether (TBDMS) + base

Removal: TBAF (source of F-)

TMS - least stable to acids and bases

TBDPS - selective for primary alcohols

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the synthesis of a tripeptide?

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is a resin?

A

An insoluble polymer in bead form about 1mm in diamter

Also called: polymer bead, resin bead, solid phase, solid support

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
How do we attach an amino acid t the resin?
Usually the C terminus of the first amino acid is attched to the support. OH attackes carbon and kicks out chloride
26
How do we attach the first amino acid to a Wang resin?
Use DCC / DIC to activate OH on the resin and do an esterification reaction
27
How do we attach the first amino acid to a Rink amide resin?
React COOH terminus with the NH2 of the resin to form an amide
28
What are the advantages of the solid support?
No purification No washing between steps
29
What are the differences between protein assembly on solid support and in solution?
Boc cannot be used to protect N terminus on solid support DCC cannot be used as activating agent as it precipitates out of solution which is undesirable using solid support - DIC has same mechanism Side chain protecting groups are generally chosen for one step deprotonation and release from the support
30
How do we cleave peptide from a Merrified resin?
Cleavage requires HF - very corrosive and toxic
31
How do you cleave the peptide from the: Wang resin acid labile derivative Sasrin resin
Acid and TFA 0.5% TFA in DCM with acid
32
What is the real synthesis of a tripeptide using Wang resin? Why is Fmoc used to protect the N terminus and not Boc?
F moc is removed with piperidine whihc doesnt affect the rest of the synthesis Boc is removed with TFA whuch cleaves the peptide from the resin and ends the synthesis
33
What are the advantages and limitations of solid support peptide synthesis?
No work up required, Can be automated No purification of intermediates possible - accumilation of impurities and incomplete coupling reactions lead to biproducts Mixture of products can be diffuclt to separate Limit on the amount of peptide that can be produced
34
What are the terms used to descirbe carbohydrates?
Monosaccharide: single sugar unit Disaccharide: two sugar units joined Oligosccharide: more than two sugar units joined together Carbohydrate: anything from mono ----\> oligo sccharide Glycoside: any carbohydrate molecules with anomeric substituent other than OH Glycoconjugate: general term for a carbohydrate covalently linked to another biomolecule
35
Why is the anomeric cnfiguration important?
anomeric OH axial = alpha anomeric OH equatorial = beta For many biological recognition events only one anomer will take part in the event
36
How can we synthesise enantiomerically pure sugars?
Prevent mutarotation - fix equilibrium in one form (replace OH with OME) Tune the experimental condition - choice of activating agent, protecting group, solvent
37
What is the anomeric effect?
The effct that determines where the equilibrium between alpha and beta anomers lies
38
What causes the anomeric effect?
hyperconjugation dipole minimisation
39
What is hyperconjugation?
For some anomeric substituents when in the axial position the antibonding orbital of the substituent lines up with the axial lone pair of the O in the ring (the non bonding orbital) The non bonding orbital can donate eletron density into the anitbonding orbital which stabalises the complex. This favours the alpha anomer This cannopt happen in a beta anomer
40
What is dipole minimisation?
In the alpha anomer the dipoles point away from each other In the beta anomer they point in the same direction so there is a large dipole moment This favours the alpha anomer
41
What two things must be decided upon when synthesising carbohydrates?
What positions the sugars are going to be linked e.g 1,3 or 1,6 The stereochemistry of the linkage e.g - alpha or beta anomer
42
How do we get efficient and selective coupling of two monomers?
Activate the donor anomeric hydroxyl to a better leaving group Prevent loss of regio/stereochemistry with protecting groups Achieve selecvtive formation of alpha or beta anomers with appropriate choice of solvent, activating agent
43
What can we use to protect non anomeric hydroxyl groups on sugars?
Trityl benzyl ether acetic acid esters benzyl or benzoyl esters
44
How do we install / remove Trityl
Thus is a sterucally demanding group - used for primary hydroxyls Installation: Trityl-Cl and base Removal: mild acid (e.g AcOH)
45
How do we instal and remove benzyl ethers?
Installation: BnBr/BnCl and base (NaH) Removal: H2, Pd/C catalyst
46
How dpo we instal and remove acetic acid esters?
Installation: AcO2, pyridine (acts as base and catalyst) Removal: NaOMe, MeOH
47
How do we instal and remove benzyl/benzoyl esters?
Installation: benzoyl chloride +pyridine Removal MaOMe, MeOH
48
How does nature acitivate the anomeric hydroxyl
- activated through coupling to a nucleoside diphosphate group (e.g UDP) Glycosyltransferases catalyse glycosidic bond formation with control over regio- and stereochemistry
49
How can we activate the anomeric OH synthetically?
Actuvation with a good leaving group can lead to the formation of a carbocation (oxocarbenium ion). The nucleophile can then attack from above or below the face of the sugar Due to the anomeric effect the alpha anomer is dominant
50
What happens when Br is used as a leaving group in the activation of carbohystrates?
All OHs are protected with with AcO2 and pyridien then the anomeric OH is converted to Br with HBr Only the beta product forms
51
Why do we only observe the beta product when Br is a leaving group?
The lone pair on the C=O of the acetate attacks the electrophilic anomeric carbon to cyclise which blocks the bottom face and prevents the alpha anomer being formed
52
How do we use trichloroacetimidate as an activating group?
Giid leaving group - must be activated by Lewis acid installation: Cl3CCN + base (NaH) TMS-OTf (imine attacks Si forming good leaving group) Only beta product observed again
53
How are thioethers used as activating groups?
Can be made into a good leaving group anomeric OH is converte to Br with HBr and then to SPH with Ag2CO3 and HSPh or the anomeric OH is directly coverted to SPh with HSPh and BF3 . OEt
54
How is SPh made into a good leaving group using acid?
NIS (N- iodo succunimide) + acid
55
How is SPh made into a good leaving group with Tf2O?
mCPBA and Tf2O
56
How can the stereochemistry of 1,2-trans glycosides be controlled?
neighbouring group participation anomeric effect solvent
57
How can neighbouring group participation control the stereochemistry of the 1,2-trans glycosides?
A cyclic oxonium ion intermediate blocks one face of the ring so that the nucleophile of the second sugar can only attack on one face When AcO in equatorial position beta anomer forms When AcO in axial position alpha anomer forms
58
In which situation does neighbouring group participation not work?
The use of HBr produces the alpha anomer despite the cyclic oxonium ion forming. The beta anomer is the kinetic product and is formed initially but equiloibratuion happens quickly diue to the acidic conditions - equilibrium lies towards the alpha anomer
59
How does the anomeric effect control the stereochemistry of the 1,2-trans glycosides?
In the absence of NGP the anomeric effect will drive formation of the alpha anomer When the 2OH is protected by something other than Ac or Bz and in the equatorial position a 1,2-cis glycoside is produced In mannose when the 2-OH is in the axial position a 1,2-trans glycoside is formed
60
How does the solvent control the stereochemistry of 1,2-trans glycosides?
Nucleophilic solvents will participate in the reaction - follow same rules as other nucleophiles The solvent nucleophile will mainly form the alpha anomer and block this face so the sugar can only attack at the equatorial position to form the beta anomer In a non-nucleophilic solvent the anomeric effect drives formation of the alpha anomer
61
How can we control the sterochemistry of 1,2-cis glycosides?
The anomeric effect intramolecular tethering
62
How does the anomeric effect influence the stereochemistry of 1,2-cis glycosides?
The anomeric effect is useful in forming 1,2-cis glycosides of gluscose or galactose where the 2-OH is pointing down (equatorial) - pushes towards the alpha anomer In mannose when the 2-OH is pointing up the anomeric effect pushes towards the 1,2-trans glycoside
63
How can intramolecular tethering be used to control the stereochemistry of 1,2-cis glycosides?
Intramolecular tethering can be used to form 1,2-cis glycosides of mannose The 2-OH must be unprotected - SiMe2Cl2 and imidazole (base) is used to to couple to sugars
64
What is the synthesis of a β(1,6) linked diasaccharide?
65
Is it possible to automate oligosaccharide synthesis?
Varying degrees of success Oligosaccharides are assembled on polystyrene Merrified resin Must control stereo- and regioselectivity Need close to 100% efficiency due to lack of purification of intermediates The glyconeer 2.1 (2017) fully automated oligosaccharide synthesiser: Mainly used to synthesis polymer of 1 sugar or repeating disaccharide
66

Core 5 (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions