Structural analysis. “Molecular Dog” by Robert Chambers.
21
Structural analysis
-
date post
19-Dec-2015 -
Category
Documents
-
view
230 -
download
10
Transcript of Structural analysis. “Molecular Dog” by Robert Chambers.
Structural analysis
H3C CH3
H3C
CH3H3C CH3
H3C
CH3
H3C CH3
HC
H
H
H
CH3
H3C
H3C CH3
CH3
H3C
H3C CH3
“Molecular Dog” by Robert Chambers
N
HH
Cl
Cl
Zoloft
N
H
H
Amphetamine - obesity treatment
N
O
Diethylpropion - obesity treatment
O
OH
H
H Dronabinol
HN
O OCH3
Ritalin
OH
O
NH2
HO
HOLevodopa
O
O
O
O
OH
OO
O
HO
NH
OH
OO
O
OTaxol
From the bark of the Pacific yew tree (kills the tree to harvest enough); or a closely related compound from the needles of the European yew tree (doesn’t kill the tree).
C&E News July 7, 2008 Volume 86, Number 27 p. 88 : an example from an illustration for a book review in the New York Times. What do you think of this as a chemical structure???
(What do you surmise the book was about?)
O
O
O
O
O
O
O
O
O
OO H2C
C
O
CH3
H
H H3C
H
H
H
H
CH3
HH
CH3 CH3
H
H
CH3
H
H
H
H
H3C
H
HOO
H
Brevetoxin B
When seas become deadly…
How many carbons in a row can you count in this molecule?____
HO O
CH3
HO
H3C
O
N
OO
O
O
OHCH3
O
O
CH3
CH3
O
H2C
H3C
CH3
CH3
Tacrolimus - immunosuppressant for organ transplantation
H3C CH3
CH3
OH
CH3 CH3
Vitamin A (trans-retinol)
The following slides are examples to consider how molecules get converted
from one to another.
Example 1: cis/trans isomerization
OH
HO OHOH
HO
HO O
OO
O
O
OH
O
O
OH
OH
OH
OO
OH
OH
HOOHHO
HO
Castalagin O
OH OH
O O
O
OH
OH
OH
OO
OH
OH
HOOHHO
HO
OVescalene
Target molecule:Potential potent topoisomerase II inhibitor
Starting point: Molecule from oak-barrel-aged wine
Example 2:
OH
HO OHOH
HO
HO O
OO
O
O
OH
O
O
OH
OH
OH
OO
OH
OH
HOOHHO
HO
Castalagin O
Acid hydrolysis
of two esters
OH OH
O
OH
O
O
OH
OH
OH
OO
OH
OH
HOOHHO
HO
O
1st intermediate
OH OH
O
OH
O
O
OH
OH
OH
OO
OH
OH
HOOHHO
HO
O
1st intermediate
Epimerization
at a chiral center
OH OH
O
OH
O
O
OH
OH
OH
OO
OH
OH
HOOHHO
HO
O
2nd intermediate
(Change of stereochemistry = epimerization)
OH OH
O
OH
O
O
OH
OH
OH
OO
OH
OH
HOOHHO
HO
O
2nd intermediate
Elimination
(Dehydration)
OH OH
O O
O
OH
OH
OH
OO
OH
OH
HOOHHO
HO
O
Vescalene
Prostratin (a molecule with potential to pull HIV out of hiding so it can be eliminated) can be synthesized from phorbol in several steps. What steps would be necessary to change the molecule phorbol into the molecule prostratin?
Phorbol: available from feedstock in quantityProstratin: found in a Samoan rainforest tree; not available from that source in sustainable quantity
Example 3:
