Chemistry Reference
In-Depth Information
Problem 16.04 (level 1; chapters 1, 3 and 7)
The enzyme fumarase catalyses the stereospecific
trans
-addition of water to fumaric acid giving (
S
)-malic acid,
and the reverse reaction, the
trans
-elimination of water from (
S
)-malic acid:
OH
H
CO
2
H
+ H
2
O
HO
2
CCH
2
CH
CO
2
H
S
HO
2
C
H
- H
2
O
fumarase
fumaric acid
(
S
)-malic acid
(a) Give systematic names with stereochemical descriptors for fumaric acid and malic acid.
(b) Show the stereochemistry of (
S
)-malic acid using wedge - dot conventions.
(c) Deduce the structure of the product from the action of fumarase on (2
S
,3
S
)-[3-
2
H]malic acid.
The enzyme malate synthase also synthesises (
S
)-malic acid from glyoxylic acid (OHC-CO
2
H) and the thioester
acetyl-coenzyme A (CH
3
CO.SCoA; this may be regarded as a source of the nucleophile
−
CH
2
CO.SCoA).
(d) Draw a mechanism for the addition reaction.
(e) Draw a mechanism for the hydrolysis of the intermediate thioester, assuming base catalysis.
(f) Indicate the stereochemistry implicit in the addition reaction. What face of the carbonyl group is attacked?
Answer 16.04
Whilst this may look like an intermediary metabolism question, it requires no knowledge of biochemistry, and is
merely a simple chemical analysis of two reactions from biochemistry.
(a) The nomenclature for a dicarboxylic acid follows from that of a monocarboxylic acid, e.g. butanoic acid
becomes butandioic acid. The 1,4-numbering is strictly redundant; the carboxylic acids must be at the ends of
the chain. Stereochemical descriptors are (
E
) for the double bond in fumaric acid, and the (
S
) configuration
stated for malic acid.
longest carbon chain is C
4
: butane
dicarboxylic acid: butan-1,4-dioic acid
E
-double bond at position 2
longest carbon chain is C
4
: butane
dicarboxylic acid: butan-1,4-dioic acid
hydroxyl at position 2
stereochemistry given
1
H
CO
2
H
OH
3
2
1
4
3
2
HO
2
CCH
2
CH
CO
2
H
HO
2
C
H
S
4
(
E
)-but-2-en-1,4-dioic acid
(
S
)-2-hydroxybutan-1,4-dioic acid
(b) Draw the carbon chain in zigzag form, put in the large carboxylic acid groups
anti
, then the substituents. The
configuration at C-2 is determined by trial and error.
only carbon 2 is chiral; at C-2 put in the H and OH
randomly and assess the chirality drawn;
it is easiest to put the group of lowest priority at the
rear (dotted) to assess the configuration.
priority 3
priority 2
H
H
CO
2
H
2
HO
2
C
3
S
HO
H
anticlockwise = S;
this is the correct configuration; if not, simply reverse it
priority 1
priority 4
