iii_2014_paper3.pdf

7/25/2019 III_2014_Paper3.pdf

1/28

NATURAL SCIENCES TRIPOS Part III

Tuesday 27th May 2014 9.00 to 12.10

CHEMISTRY: PAPER 3A

Candidates should attempt FOUR questions, taken from at least THREE different sections.

Where a question is divided into sections, the approximate division of marks betweensections is indicated at the end of the question.

Linear graph paper is available if required.

A Periodic Table, the structures of the amino acids and nucleotide bases, the values ofphysical constants, character tables and selected mathematical formulae will be found inthe data book provided.

Write on ONE side of the paper only.

The answers to each question should be returned separately.

A separate cover sheet for each question should be completed.

Calculator students are permitted to use an approved calculator.

STATIONERY REQUIREMENTS SPECIAL REQUIREMENTS

Graph paper (2 sheets) Department of Chemistry Data BookLined paper Question record card

Rough work pad

You may not start to read the questions printed on

the subsequent pages of this question paper until

instructed that you may do so by the Invigilator.

During the first 10 minutes of the examination

you are permitted to read the paper, but you may

not start writing your answers until this time has

elapsed.

7/25/2019 III_2014_Paper3.pdf

2/28

7/25/2019 III_2014_Paper3.pdf

3/28

NATURAL SCIENCES TRIPOS Part III

Tuesday 27th May 2013 9.00 to 10.40

CHEMISTRY: PAPER 3C

Candidates should attempt any TWO questions.

Where a question is divided into sections, the approximate division of marks betweensections is indicated at the end of the question.

Linear graph paper is available if required.

A Periodic Table, the structures of the amino acids and nucleotide bases, the values ofphysical constants, character tables and selected mathematical formulae will be found inthe data book provided.

Write on ONE side of the paper only.

The answers to each question should be returned separately.

A separate cover sheet for each question should be completed.

Calculator students are permitted to use an approved calculator.

STATIONERY REQUIREMENTS SPECIAL REQUIREMENTS

Graph paper (2 sheets) Department of Chemistry Data BookLined paper Question record cardRough work pad

You may not start to read the questions printed on

the subsequent pages of this question paper until

instructed that you may do so by the Invigilator.

During the first 10 minutes of the examination

you are permitted to read the paper, but you may

not start writing your answers until this time has

elapsed.

7/25/2019 III_2014_Paper3.pdf

4/28

2

SECTION A

L1 Catalysis for chemical synthesis

36

Answer allparts of the question.

(a) Suggest reagents and conditions for accomplishing the multi-step transformation ofDintoE, and provide mechanisms.

O

SiMe3

OH

O

D E

(b) Provide reagents and conditions for the synthesis of the prostaglandin derivative Ifrom fragments F, Gand H(fragments Fand Hare enantiomerically pure and nofurther chiral catalysts or chiral reagents are necessary). Provide mechanisms foryour transformations and comment on the origins of stereocontrol where it arises inyour approach.

O

TBSO

CO2Me

O

TBSO

I

F

G

H I

OTBDPS

C5H13

C5H13TBDPSO

CO2Me

B

[Qu.36continued on next page]

7/25/2019 III_2014_Paper3.pdf

5/28

3

[Continuation of Qu.36]

(c) Compound J, of interest in medicinal chemistry, can be prepared from fragmentsKandL(structures shown) and one other fragmentM(structure not shown). FragmentMprovides the all of the remaining carbon atoms needed.

Suggest a structure for fragment M, and suggest a synthetic approach to J, usingfragments K, L, andM. You should provide suggested conditions, mechanisms andrationalisation of any stereochemistry and chemoselectivity which arises.

NH

O

Cl

N

N

Bn

N

N

Bn

B

HO

OH

NH2

I

Cl

J K L

Approximate division of marks: (a) 30%, (b) 35%, (c) 35%.

[TURN OVER

7/25/2019 III_2014_Paper3.pdf

6/28

4

37


(a) Explain the outcome of subjecting ()-Ato the following catalytic transformation.Provide a rationale for the control of stereochemistry as part of your answer andclearly indicate the sense of induction at the two marked (*) chiral centres in theproductB.

()-A B

O

Me

O

OMe

NHCOPh

(R)-RuCl2(BINAP)

H2, CH2Cl2, 50 C

OH

Me

O

OMe

NHCOPh

*

*

100% yield, 87% de, 98% ee

PPh2

PPh2

(R)-BINAP

(b) Provide a mechanistic explanation of how C and D are transformed into F usingcatalystE. In your answer, include a detailed description of how the stereochemistryis controlled.

(20 mol%)

OHCMe

CO2t-Bu

CNPh

OHCPh

NC CO2t-Bu

NH

Ph

OTESPh

C D

E

F


7/25/2019 III_2014_Paper3.pdf

7/28

5


(c) Explain the outcome of the catalytic enantioselective transformation in whichGandHare transformed into I. Provide a detailed model that explains the stereochemistryobserved inIas part of your answer.

G H

O

Ph

O

OH

Ph

O

Ot-Bu

HO

Me

Me

Me

N N

O O

Me Me

Ph Ph

Cu

2+

2 OTf

CH2Cl2, 23 C

I

(10 mol%)

(d) Propose a synthesis ofJthat uses asymmetric catalysis. Your synthesis can involvemultiple steps and you may use any common reagents. Provide a detailed descriptionof how the stereochemistry is controlled.

OMe

J

Approximate division of marks: equal for each part.

[TURN OVER

7/25/2019 III_2014_Paper3.pdf

8/28

6

SECTION B

L2 Solid Electrolytes

38


Titania is often oxygen-deficient relative to the stoichiometric composition, TiO2. Thisnon-stoichiometry can be written as either: (i) TiO2xor (ii) Ti1+yO2.

(a) What types of defects are expected to be present in non-stoichiometric titania asexpressed by the formulae (i) and (ii)?

(b) Write down defect reactions, in KrogerVink notation, that give rise to the non-stoichiometric compositions (i) and (ii). Comment on the effects of this oxygen defi-ciency on the dominant electronic charge-carrier type in non-stoichiometric titania.

(c) Hence obtain expressions for the concentration of the dominant electronic chargecarriers in non-stoichiometric titania at high temperatures, corresponding to formulae(i) and (ii), making clear any assumptions made.

Now consider the effects of aliovalent doping of (stoichiometric) titania with eithertrivalent (e.g. Ga3+ or Y3+) or pentavalent (Nb5+) ions present in their correspondingoxides.

(d) Write down defect reactions, in KrogerVink notation, that account for all possibili-ties of aliovalent doping of titania with such trivalent and pentavalent ions.

(e) The ionic radii of the cations concerned are: r(Ti4+) = 0.61 ; r(Ga3+) =0.61 ;r(Y3+) = 0.9 ;r(Nb5+) = 0.64 . Comment on the likelihood of the defect reactionsin (d) occurring, given these structural data.

(f) Comment on the effects of aliovalent doping with trivalent and pentavalent ions onthe resulting oxygen-ion conductivity of titania.

Approximate division of marks: (a) 10%, (b) 15%, (c) 30%, (d) 15%, (e) 20%, (f) 10%.

7/25/2019 III_2014_Paper3.pdf

9/28

7

39


(a) What are the common features of, and differences between, ionic diffusion in solidsand liquids?

(b) In a crystalline solid electrolyte, -Li3PO4, Li+ ions can diffuse in three mutuallyorthogonal directions (along x, y and z axes) by a direct interstitial mechanism. Thelengths of individual diffusional jumps and heights of the potential energy barriersbetween interstitial positions along the x-, y-, and z-axes are equal to a, b, c and Ea,Eb, Ec, respectively. The attempt frequency, 0, of diffusional jumps is the same forall directions.

(i) Determine how the mean-squared displacement of Li+ ions depends on time.

(ii) Given that the electric current density depends on an external electric fieldaccording to the following expression,

j = nQ20

2kBT

j=nn(i)

eEi j/(kBT)ri jri j E

(1)

explain the meaning of all quantities and notations used in this formula. Whatis the relation between Ei jand Ea,Eb,Ec?

(iii) Using Eq. (1), derive the expression for the conductivity tensor, specifyingall its elements.

(iv) Calculate the smallest non-zero component of the conductivity tensor at roomtemperature, T = 300 K, ifa = 4.1 , b = 3.4 , c = 7.2 , Ea = 0.21 eV,Eb =0.23 eV,Ec =0.35 eV,0 =1013 s1 andn =1022 m3.

Approximate division of marks: (a) 10%, (b) (i) 30%, (ii) 10%, (iii) 30%, (iv) 20%.

[TURN OVER

7/25/2019 III_2014_Paper3.pdf

10/28

8

SECTION C

L3 Electronic Structure of Solid Surfaces

40


(a) Explain concisely the operating principle of a Mott polarimeter and indicate how itmight be employed to quantify the net spin polarisation of valence electrons at amagnetic surface. Clarify any constraints upon the experimental geometry that mayneed to be considered in order to obtain unambiguous results.

(b) The net spin polarisation of a clean Ni{111}surface is found to be enhanced relativeto that of bulk Ni, but is suppressed upon adsorption of CO. Give an expression formagnetic susceptibility within the Stoner model, and use it to explain qualitativelywhy this behaviour is observed.

(c) A clean Cu{111} surface possesses a Shockley state whose scattering offsurface stepsgives rise to an oscillation in the Fermi-level electron density,(y), visible in scanningtunnelling microscopy (STM) and described by

(y) = 01 J0(2kFy)

where kFis the Fermi wavenumber of the surface-localised state, yis the distance

from the step edge, and0is the Fermi-level electron density far from the step.Upon applying a strong magnetic field, the Shockley state is split into two compo-nents, corresponding to spin-up and spin-down electrons, with rigidly offset energiesand hence differing Fermi wavenumbers. If the spin-up electrons now have wave-number kF +kFand the spin-down electrons have wavenumber kFkF(which isreasonable so long askFkF) use the asymptotic limit

limA

J0(A +B)

2A

cos(A +B 3/4)

where B A, to show that the oscillations (i.e. spin-up plusspin-down) will nowfollow the form

(y) =0

1 1kFy

cos(2kFy 3/4)cos(2kFy)

.


7/25/2019 III_2014_Paper3.pdf

11/28

9


(d) For a particular magnetic field strength, fitting the equation derived above to oscilla-tions observed in STM yields best-fit values ofkF =0.19 1 andkF =0.005 1.For the unperturbed surface, on the other hand, Angle-Resolved Ultraviolet Photo-emission Spectroscopy (ARUPS) confirms the value kF = 0.19 1, and reveals azone-centre binding energy of 0.39 eV.

By how much must the spin-up and spin-down Shockley states be rigidly offset inenergy relative to the Shockley state of the unperturbed surface?

Approximate division of marks: (a) 30%, (b) 20%, (c) 20%, (d) 30%.

[TURN OVER

7/25/2019 III_2014_Paper3.pdf

12/28

10

41


(a) A particular metal adopts the simple cubic crystal structure, and has bulk bands withina three-dimensional Brillouin zone (of side-lengthG) approximated by

(kx, ky, kz) = EF Wcos(2kx/G) + cos(2ky/G) + cos(2kz/G) + 2

whereW =5 eV controls the bandwidth and EF =25 eV is the Fermi energy.

The projection of this bulk Brillouin zone onto the two-dimensional Brillouin zone ofthe (110) surface is shown below, together with the projected bulk bands. How wideis the projected band gap at Band , and what is the projected bandwidth at A?

(b) If image states exist at this metal surface, they must satisfy the Schrodinger equation

d2d2

+ 1

=0

where = (2)1/2zand = (8)1/2 are defined to be real and atomic units areused.

Assuming that the image state eigenfunctions take the form

= F() e

with

F() =

q=1

aqq

show that the polynomial coefficients,aq, must satisfy

aq+1

aq=

2q +q(q + 1)

.


7/25/2019 III_2014_Paper3.pdf

13/28

11


Hence show that the resulting discrete set of zone-centre energy eigenvalues, , takethe form

= 132n2,

wherenis an integer.

(c) Assuming a work function of =5 eV and that the lowest energy image state remainsbelow the vacuum level throughout the surface Brillouin zone, in which regions of thesurface Brillouin zone should one expect such a state to be well-defined and hencepotentially observable?

(d) For the lowest energy image state, calculate the distance from the image plane

(i.e.z =

0) at which the electron density reaches its maximum value.


[TURN OVER

7/25/2019 III_2014_Paper3.pdf

14/28

12

SECTION D

L4 Organic solids

42


(a) Define what is meant by crystal engineering with regard to organic molecular solids.

(b) Halogen bonding is frequently cited as an important interaction in crystal engineering.How would use of the Cambridge Crystallographic Database help in identifying theimportance of such an interaction in an organic crystal? How would you determinefrom the observed intermolecular distances whether such an interaction existed withina particular crystal structure?

(c) The figure below illustrates a group of molecules for which attempts were made toprepare a series of cocrystals based on the shown supramolecular motifs. Outlinewhat trends you might expect to see in the melting point (if any) for (i) the bromoand iodo-based cocrystals and (ii) the substituents X and Y in the non-halogenatedmolecules.

+X Y

X, Y = O, NH, S

I

F F

I

FF

Br

F F

Br

FF

X Y I

F F

I

FF

X Y I

F F

I

FF

X Y Br

F F

Br

FF

X Y Br

F F

Br

FF

(d) Discuss the crystallographic factors which determine whether diacetylene monomersare able to undergo lattice controlled polymerization. Outline a strategy that could

be followed in the use of halogen bonding to engineer into a cocrystal the necessaryarrangement for polymerisation to occur.


7/25/2019 III_2014_Paper3.pdf

15/28

13

43


(a) Outline the strategy that would be adopted to predict computationally the likelypolymorphic forms of a small rigid organic molecule. What criteria would beapplied to discriminate between the possible structures to estimate their likelihoodof formation?

(b) What additional factors would need to be considered if the molecule was not rigid buthas various possible conformational structures?

(c) How might the possibility of a crystalline hydrate being formed be investigated usingthe output from a Crystal Structure Prediction (CSP) exercise?

(d) Transmission electron microscopy (TEM) is a technique for obtaining diffraction datafor small micron-sized organic crystals. What are the advantages and limitations ofTEM in obtaining electron diffraction data for such materials?

(e) Outline the process which would be followed in order to use CSP to determine thestructure of a possible new polymorph which has been identified by TEM.

Approximate division of marks: (a) 30%, (b) 10%, (c) 15%, (d) 25%, (e) 20%.

[TURN OVER

7/25/2019 III_2014_Paper3.pdf

16/28

14

SECTION E

L5 Chemical dynamics

44


(a) Theside-side time-correlation function Css(t) for a gas-phase reaction can be written

Css(t) = 1

(2)3N

V

exp(HN) h(q q) h(qt q) drNdpN

where Nis the number of participating atoms, =1/kBT, kBis the Boltzmann con-stant, and

V. . . drNdpN denotes an integral over the phase-space volume enclosing

the reactants.(i) Define the termsHN,q,q, and explain the purpose of the heaviside functions.

(ii) Derive theflux-side time-correlation function Cfs(t) fromCss(t).

(iii) By sketching a graph and giving relevant equations, show howCfs(t) is used tocalculate the rate of a gas-phase reaction.

(b) For a one-dimensional system, with potential energy surfaceV(q):

(i) Prove that thermal rate constantk(T) is independent of dividing surface.

(ii) Obtain the transition-state-theory (TST) approximation tok(T), stating clearlyyour assumptions.

(iii) Prove that the TST approximation gives an upper bound tok(T).

(c) Consider a two-dimensional system confined to the xy plane and with potentialenergy

V(x,y) =cxy

where cis a constant. Derive the form and position of the optimal dividing surfacefor which the TST approximation is closest to k(T) for this system. Under whatconditions will this approximation become exact for this system?


7/25/2019 III_2014_Paper3.pdf

17/28

15

45


(a) The intersecting parabola construction is a convenient potential energy surface modelpopular in theoretical chemical dynamics. For condensed phase reactions the par-abolic curves can also be interpreted as potentials of mean force. Two such quadraticpotentials of mean force for reactant aand productbcan be written as

Aa(x) =

2(x xa)

2

Ab(x) = A +

2(x xb)2

where x is the reaction coordinate.

(i) The reorganization energy for the reaction is defined as

Er = Aa(xb) Aa(xa)

Verify that the reorganization energy can also be written asEr = Ab(xa) Ab(xb).

(ii) Find the pointx where the curves cross and show that for A =0 the crossingpoint is midway betweenxaand xb.

(iii) A

= Aa(x

) Aa(xa) is the activation free energy of the forward reaction.Derive an expression for A in terms ofAandEr.

(iv) Determine , the derivative of A with respect to Aat fixed Er. Sketch thefree energy surfaces for A = Er, A = 0 and A = Erand determine thecorresponding values of.


[TURN OVER

7/25/2019 III_2014_Paper3.pdf

18/28

16


(b) The energy gap is the vertical energy difference between the potential energysurfaces of reactant and product with all atomic coordinates RN fixed.

E = EbRN

Ea(RN)

Equating the reaction coordinate x with the energy gap E leads to a model forreaction rate constants.

A(E)

E

EbEa

0

Ab !E)Aa !E)

EaEb

Aa(E) andAb(E) are the potentials of mean force generated by the potential energysurfacesEa(RN) respectivelyEb(RN). A fundamental theorem in statistical mechanicsstates that the difference in the potentials of mean force at a given value of the energygap is the energy gap itself.

Ab(E) Aa(E) = E

This theorem is unique for energy gaps and is not valid for general reaction coordi-nates x.

(i) Verify thatEcan be used as a reaction coordinate distinguishing reactant andproduct.

(ii) Show that Er = Ea = Eb where Eris the reorganization energy definedin (a) (i) and Ea and Eb are the energy gap coordinates at the minima ofthe parabolic potentials of mean forceAa(E) andAb(E) for a thermoneutral

reaction (A =0, see figure).(iii) Show that the relation obtained in (b) (ii) implies that the activation free energy

A decreases for increasing values ofwhereis the spring constant specify-ing the curvature of the quadratic potentials of mean force Aa(E) andAb(E)(see (a)). How can we rationalize this counterintuitive prediction claiming thatthe stiffer the environment the faster the reaction?

Approximate distribution of marks: (a) (i) 10%, (ii) 20%, (iii) 20%, (iv) 10%, (b) (i) 10%,(ii) 20% (iii) 10%.

7/25/2019 III_2014_Paper3.pdf

19/28

17

SECTION F

L6 Main group organometallics

46


(a) Carbon-based alkenes are planar, whereas the heavier alkene analogues of Group 14,including the germylene1, havetrans-bent arrangements.

Ge Ge

ArAr

Ar

ArGe Ge

(Dipp = 2,6-Diisopropylphenyl)

N N DippDipp

L =

L

L

1 2

89.9

(i) Explain, using valence-bond diagrams, why the C and Ge derivatives adoptdifferent geometries.

(ii) How are these differences reflected in the solution behaviour and reactivity ofR2C=CR2vsthe heavier alkenes of group 14?

(iii) Species2 is stabilised by donation from two N-heterocyclic carbenes (L). Usea valence-bond approach to show how the bonding in 2differs from1.

(b) Explain why the bis-cyclopentadienyl-aluminium cation 3has a linear structure butbis-cyclopentadienyl-germanium 4is bent.

GeAl+

3 4


[TURN OVER

7/25/2019 III_2014_Paper3.pdf

20/28

18


(c) The cyclobutadienyl dianion5reacts with one equivalent of GeCl2to give6.

SiMe3

SiMe3Me3Si

Me3Si

2-

-

2Cl+GeCl2 SiMe3

Ge

Me3Si

Me3Si SiMe3

5 6

Describe the bonding within6, considering it as:

(i) an electron-deficient cluster;

(ii) a metal-ligand-complex.

Approximate division of marks: (a) 45% (b) 30%, (c) 25%.

7/25/2019 III_2014_Paper3.pdf

21/28

19

47


(a) Suggest aggregation states for lithium enolatesAandB. Rationalise your answer.

A

But

OLiOLi

NMe2

B

(b) Explain the two observations below.

ZnMe2

O O

Zn(TMP)Me

O O

Li TMPH Li MeH

AlMe3

O O

Li TMPH no reaction

N

TMPH =

H

2,2,6,6-tetramethylpiperidine


[TURN OVER

7/25/2019 III_2014_Paper3.pdf

22/28

20


(c) Reaction ofCwith tBuLi in Et2O givesDand gaseousE.

ON

C

In the solid-stateDexists in two forms (each with formula weight=

489) incorporat-ing Li+ ions that are bonded only to O atoms. Cryoscopic measurements in benzenesuggest an average molecular mass of 249 6 in solution. The 1H NMR spectrum ofDin d6-benzene is as follows:

7.266.54 (m, 3H), 4.50 (sept., lH), 3.48 (q, 12H), 3.05 (sept., lH), 2.70 (q, lH),2.21 (q, 2H), 2.04 (d, 3H), 1.98 (t, 3H), 1.62 (d, 3H), 1.49 (d, 3H), 1.30 (t, 18H),0.81 (d, 3H), 0.78 (d, 3H) ppm.

(i) Sketch the molecular structure ofD in the solid state.

(ii) Suggest how the structure ofDchanges upon dissolution in benzene.(iii) Assign the 1H NMR spectrum ofD.


7/25/2019 III_2014_Paper3.pdf

23/28

21

SECTION G

L8 Total Synthesis

48


The following scheme describes Overmans synthesis of the alkaloid natural product,actinophyllic acidJ. Answer the following questions relating to the synthesis below.

N

CO2tBu

CO2tBu

Mg(OMe)2, MeOH

then

NO2

COCl NO2

O

CO2tBu

CO2tBuNH

CO2tBu

CO2tBu

A B C D

NH

CO2tBu

CO2tBu

NBocO

NBocO

Br

DMF, rt

E

F

LDA (3.2 equivalents)

[Fe(DMF)3Cl2]+[FeCl4]

(3.5 equivalents)

THF, 78 C to rt

Hint : [Fe(DMF)3Cl2]+[FeCl4]

is a source of Fe3+

NH

BocN

CO2tBu

CO2tBu

O

G

(i) F3CCO2H, rt

(ii) (CH2O)n, MeCN, 70 C

(iii) HCl/MeOH then aq. Na2CO3

then F3CCO2H

H

HN

OH

HO2C

O

HN

HN

MeO2C H

F3CCO2O

LDA, CH2O, THF

then HCl Cl

I J

CeCl3, THF, 78 C

MgBr


[TURN OVER

7/25/2019 III_2014_Paper3.pdf

24/28

22


(a) Account for the transformation ofAintoC, explaining the role of the Mg(OMe)2.

(b) Provide reagents and conditions for the transformation of Cinto D, explaining themechanism of your proposed reactions.

(c) Explain the reaction ofDandEin the formation ofF.

(d) Propose a mechanism that explains howGis formed from F.

(e) Draw the structure forH, explaining how the stereochemistry arises. What is the roleof CeCl3?

(f) Account for the formation ofHtoI, and fromItoJ, providing a detailed mechanisticrationale for the steps involved.

Approximate division of marks: (a) 10%, (b) 10%, (c) 10%, (d) 20%, (e), 10%, (f) 40%.

7/25/2019 III_2014_Paper3.pdf

25/28

7/25/2019 III_2014_Paper3.pdf

26/28

24


(a) Explain how Cis formed from the reaction of Aand B. Provide a stereochemical

rational for the production of isomer shown.(b) Account for the stereochemical outcome in the transformation ofC toD.

(c) Provide a mechanism to explain the conversion ofEtoF.

(d) Provide a detailed mechanistic explanation for the formation of H from G. Youranswer should include a three-dimensional diagrammatic explanation of the stepsinvolved. Comment on the unusual nature of bridged bicyclic framework withinH.

(e) Explain the transformation ofHtoI.

(f) How would you convert Iinto J. Provide reagents and conditions for each step inyour proposed synthesis.

Approximate division of marks: (a) 15%, (b) 10%, (c) 25%, (d) 25%, (e), 10%, (f) 15%.

7/25/2019 III_2014_Paper3.pdf

27/28

25

SECTION H

L9 Biosynthesis

50

Answer bothparts of the question.

(a) Give a plausible biosynthetic pathway to the fungal metabolite marcfortine,A, fromprimary metabolites, giving brief mechanistic details for the ring-forming reactions.

N

NMe

HN

O

O

O Omarcfortine A

(b) Outline the biosynthetic pathway to alkaloids of general structure B from primarymetabolites, giving brief mechanistic details. What isotopic labelling experimentwould you do to confirm your biosynthetic pathway? Show the labelling pattern in Bthat would result from your experiment.

NMe

O

O

OR

O

R'

OB

Approximate division of marks: (a) 60%, (b) 40%.

[TURN OVER

7/25/2019 III_2014_Paper3.pdf

28/28

26

51


Granaticin is produced by a number of Streptomycete bacteria, and is generated by fusinga polyketide with a glucose-derived sugar via two carboncarbon bonds.

O

OOH

OH

O

O

O

O

OH

OH

H

granaticin

sugar-derived

OHOHO

OH

OH

OH

glucose

(a) The polyketide is generated by a type II polyketide synthase. Propose a biosyntheticpathway to the polyketide, including the names of the different types of enzymeinvolved, and the tailoring steps required. Mechanisms are not required.

(b) If sodium [1-13C]acetate and [1,2-13C]acetate are separately fed to a granaticin-producing organism, describe the differences that would be expected in the 13C NMRspectrum obtained for granaticin from each feeding experiment, compared with thespectrum of unlabelled granaticin. Show the incorporation pattern of the 13C in

granaticin that you would expect to observe from these experiments based on thepathway proposed in part (a).

(c) Discuss the probable origin of each of the oxygen atoms in the polyketide, anddescribe experiments to confirm your hypothesis.

(d) Predict the sugar precursor, and describe the biosynthetic pathway to it from glucose.

(e) Propose a plausible mechanism for the formation of the two carboncarbon bondsbetween the sugar and polyketide moieties.

Approximate division of marks: (a) 40%, (b) 20%, (c) 10%, (d) 20%, (e) 10%.

END OF PAPER

iii_2014_paper3.pdf

Documents