Chemistry Reference
In-Depth Information
Box 10.9 (continued)
N
Me
base
OH
N
O
Me
not favourable; enolate anion not
stabilized by extra conjugation
H
OH
O
O
base
H
OH
O
HO
hydrolysis of ester
(
−
)-littorine
O
(+)-phenyl-lactic acid
Additionally, note that base hydrolysis of hyoscyamine gives (
±
)-tropic acid and tropine, with racemization
preceding hydrolysis. Base hydrolysis of littorine gives optically pure phenyl-lactic acid, so we deduce that
hydrolysis is a more favourable process than racemization.
Box 10.10
Epimerization of
L
-amino acids to
D
-amino acids during peptide biosynthesis
Many natural peptide structures, especially the
peptide antibiotics
such as dactinomycin and ciclosporin (see
Box 13.10), contain one or more
D
-amino acids along with
L
-amino acids in their structures. This contrasts with
most proteins, where all the amino acid constituents are of the
L
-configuration (see Section 13.1). It is now
known that the biosynthetic precursors of the
D
-amino acids are actually the corresponding
L
-analogues, and
that an enzymic epimerization process through an enol-type intermediate is involved. However, this does not
appear to involve epimerization of the free
L
-amino acid followed by incorporation of the
D
-amino acid into the
growing peptide chain. There are good reasons for this. Enolization in base does not occur, since ionization of the
carboxylic acid group predominates (see Section 10.7). Enolization in acid is also prevented, because the basic
amino group would be protonated rather than the carbonyl (see Section 4.11.3). In fact, epimerization appears
to take place after the
L
-amino acid has been incorporated into the peptide, and is thus occurring on an amide
substrate.
A simple example is the tripeptide precursor of the
penicillin antibiotics
, called ACV, an abbreviation for
δ
-aminoadipic acid (an
unusual amino acid derived by modification of
L
-lysine),
L
-cysteine, and
L
-valine (not
D
-valine).
-(
L
-
α
-aminoadipyl)-
L
-cysteinyl-
D
-valine. The amino acid precursors for ACV are
L
-
α
S
H
2
N
H
2
N
R
H
2
N
S
CO
2
H
SH
CO
2
H
CO
2
H
CO
2
H
L
-
α
-aminoadipic acid
L
-cysteine
L
-valine
synthesis of tripeptide
from amino acids
N
H
N
H
2
N
H
2
N
SH
S
penicillins
CO
2
H
O
N
CO
2
H
O
NH
O
O
D
formation of
fused ring system
CO
2
H
CO
2
H
ACV
isopenicillin N
