Chemistry Reference
In-Depth Information
RCH
2
CHNH
2
COOH + H
2
O → RH + CH
3
COCOOH + NH
3
(I)
RCH
2
CHNH
2
COOH + R'H → RH + R'CH
2
CHNH
2
COOH + RH
(II)
R'H + CH
3
COCOOH + NH
3
→ R'CH
2
CHNH
2
COOH + H
2
O
(III)
L-Tyrosine and related aminoacids can be synthesized in very high yields through the reverse of -elimination
(III). In the case of L-DOPA synthesis by the resting cells of
Erwinia herbicola
, high concentrations of L-DOPA are
obtained in the reaction mixture (Fig.
14
). Ajinomoto Co. Ltd started the commercial production of L-DOPA via this
new biological route [69]. The enzymatic process shows a fivefold improved productivity in comparison with the
chemical process, and with a significant reduction in the time required to complete the process (Table
2
) [69].
O
COOH
+
COOH
Erwinia herbicola
(Tyrosine phenol lyase)
HO
+ H
2
O
NH
2
HO
HO
OH
+
L-DOPA
NH
3
Figure
14:
The new synthetic process for L-DOPA.
Table 2:
Comparison between the enzymatic and the chemical processes for the production of L-DOPA [70].
Enzymatic synthesis
Chemical synthesis
Main starting materials
Catechol, pyruvic acid, and ammonia
Vainillin, hydantoin, H
2
, (CH
3
CO)
2
O
Number of individual reactions
1
8
Reaction by-products
H
2
O
NH
3
, CO
2
, CH
3
COOH
Optical separation
Not necessary
Separation of reaction intermediates (acetyl-
D/L-veratroylglycine) with the enzyme acylase
and racemisation of the D-compound
Production facilities
(reaction and isolation)
Versatile equipment
Special plant is required
Time required for production
Approx. 3 days
Approx. 15 days
The Chiral Pool: Carbohydrates and Derivatives
Carbohydrates are renewable, often cheap and abundantly available, but as chiral building blocks they are generally
available only in one enantiomeric form and rarely bear a close structural relationship to a target. They suffer from a
profusion of chirality.
The carbon chains are generally too long, requiring costly transformation to smaller, more useful species. Mannitol
is an exception; the symmetry of the molecule permits cleavage to two identical subunits, which are still chiral. This
is utilized in the synthesis of (
S
)-solketal (
4
) [71] from D-mannitol (
3
) (Fig.
15
) and in the synthesis of 2,3-
O
-
isopropylidene-D-glycerol in a convenient procedure reported by Emons
et al.
[72].
Utilization of D-glucose in the classical Reichstein-Grussner process for L-ascorbic acid (vitamin C) is a major, and
one of the earliest, industrial examples of a chiral pool substance being used in synthesis (Fig.
16
), albeit for the
production of further “pool” material. The process was developed in the 1920s. The C
2
and C
3
glucose stereogenic
centers are changed into the C
4
and C
5
carbon atoms of ascorbic acid. In this way, none of the reactions of the
synthetic pathway need to be stereoselective. The only important problem to be solved is the selective oxidation of
one of the primary and secondary hydroxyl groups of D-sorbitol.
