Natural Products Assignment #2
CHEM 7450 / 4580
Natural Products Chemistry and Biosynthesis
Dr. John L. Sorensen
Assignment #2 (Feb 10th 2021)
Due Date: 5:00 pm Thursday Feb 17th 2022
Question #1: (20 Marks)
Answers can be done by hand or by ChemDraw
The polyketide multicolosic acid is produced in fermentation cultures of a strain of the fungus
Penicillum multicolor. The results of biosynthetic experiments are summarized below and
suggest that an initial polyketide synthase product is further transformed in a series of post-
PKS reactions.
Extraction of the fermentation liquor of P. multicolor results in a crude extract that is treated
with diazomethane to methylate ca
oxylic acid groups to simplify purification. Three separate
feeding experiments with the labeled acetates shown below.
The incorporation pattern for [1,2-13C] sodium acetate was determined by 13C NMR
spectroscopy and these results are summarized in a table below. The chemical shift and
multiplicity (as determined in the natural abundance spectra) of each ca
on signal is given in
the second column. In the third column is given the coupling observed in dimethyl O–
multicolosic acid when the doubly labeled acetate is fed to the culture.
(See Over for Table)
O
MeO
OMeO
O OMe
O
O
O
ONa
O
Na
D
D
D
Dimethyl O-methylmulticolosate
P. multicolo
fermentation cultures
P. multicolo
fermentation cultures O
MeO
OMeO
O OMe
O
D
D D D D
1
23
4
5
6 7 8 9
1011
O
O
Na
1. Extraction
2. CH2N2
3. Purification
1. Extraction
2. CH2N2
3. Purification
P. multicolo
fermentation cultures O
MeO
OMeO
O OMe
O
1. Extraction
2. CH2N2
3. Purification
Results given in table belowHINT: R OH
O
CH2N2
R OMe
O
Natural Products Assignment #2
Ca
on d (
13C ppm)
(multiplicity)
J
13C – 13C
(Hz)
[1-13C]
acetate
incorporation
[2-13C]
acetate
incorporation
XXXXXXXXXXs) +
XXXXXXXXXXs) 45 +
XXXXXXXXXXs) +
XXXXXXXXXXs) 90 +
XXXXXXXXXXt) 45 +
XXXXXXXXXXt) 35 +
XXXXXXXXXXt) 35 +
XXXXXXXXXXt) 55 +
XXXXXXXXXXs) 55 +
XXXXXXXXXXd) 90 +
XXXXXXXXXXs) +
CH3O-
(C-11 O–methyl XXXXXXXXXXq)
CH3O-
(C-9 O–methyl XXXXXXXXXXq)
CH3O-
(C-3 O–methyl XXXXXXXXXXq)
i) (5 marks) Re-draw the structure of dimethyl O–
methylmulticolosic and indicate, based on your analysis
of the NMR data above, the pattern of intact acetate
incorporation.
Use the labeling convention below to indicate acetate
units that are incorporated intact, and (or) labels that
esult from isolated acetate derived ca
ons that result from the cleavage of an acetate C–C
ond.
ii) (5 marks) Shown at right is 6-pentylresorcylic acid, the proposed
product of the polyketide synthase enzyme responsible for multicolosic
acid biosynthesis. Re-draw the structure and indicate the pattern of
acetate incorporation from [1,2-13C] sodium acetate that would be
consistent with the results in the table and the polyketide origin of this
molecule.
iii) (10 marks) Propose a detailed mechanism for the biosynthesis of
dimethyl O–methylmulticolosic that is consistent with the data provided
above. Ensure that the pathway that you propose takes into account
not only the double labeling experiment but also the positioning of the
oxygen and deuterium atoms derived from acetate. Provide a
ief
ational for the significant steps in your pathway.
(HINT: The compound at right is not an intermediate in the pathway)
CO2H
OH
HO
*Intact
Acetate
Acetate C-1
derived
label
Acetate C-2
derived
label
O
O
Na
OH
HO