298
MAURICE WELSCH
carboxyphenazine (or griseolutic acid), the griseoluteins A and Β, which
are 9-methoxy-l-carboxyphenazines bearing, respectively, in position 6,
the side chain:
- CH 2 —Ο—CO—CH 2 OH
and
—CH 2 —O—CHOH—CH 2 OH
It should be stressed that, despite the great resemblance of the griseoluteins, only slight cross-resistance is observed between the two antibiotics, and also that, despite the similarity of 1,6-dihydroxyphenazine
and iodinin, the former is specifically antifungal whereas the latter is
antibacterial.
A relation with the shikimic acid route is also probable for the
biosynthesis of the quinoxaline moiety (LXXXI) of antibiotics of the
echinomycin (LX) family and for the quinoline nucleus (LXXXII)
common to the pyo compounds of Pseudomonas aeruginosa. They include
derivatives of 4-oxyquinoline [e.g., 2-n-heptyl, 2-n-nonyl (and their Noxides), 2-n-A
1
-nonenyl 2-n-undecyl-N-oxide] and the 2-n-heptyl-3-oxy4-quinolone. These compounds may arise from the combination of
anthranilic acid with a fatty acid followed by, first, oxidative decarboxylation, and next, reduction. The possibility of direct production from
tryptophan, via kynurenine, has however not been ruled out.
According to Chambers et al. (242), the C 6 -C 3 coumarin moiety of
novobiocin (XVI), as well as the C 6 -Ci fragment to which it is linked
by an amide bond, originate from tyrosine. The cinnamic acid moiety
which, in homomycin (IX) and related antibiotics, is bound to an amino
sugar by an amide linkage, is also likely to be formed via the shikimic
acid pathway, and so is the p-aminobenzoic acid of the amicetin group
of antibiotics (XV).
Little is known of the biosynthesis of chloramphenicol (LXXXIII) by
Streptomyces venezuehe. Contrary to expectation, C
14
-labeled p-nitrophenylserinol and dichloroacetic acid were found not to be incorporated
into its molecule. The presence of the phenylpropane skeleton, however,
suggests its relation to the common aromatic amino acids and the
probability of its origin via the shikimic acid pathway.
The occurrence, in chloramphenicol, of the dichloroacetyl and aryl
nitro groups are rather unusual features for a natural product. The latter,
however, is also found in aureothin (LXXXIV) a by product found in
the cultures of aureothricin-producing S. thioluteus. Α nitro group is
also present in azomycin (LXXXV), a heterocyclic antibiotic produced
by Nocardia mesenterica and Streptomyces eurocidicus, and in the aliphatic antibiotic bovinocidin, N0 2 —CH 2 —CH 2 —COOH, a substance,
weakly active against Mycobactenum tuberculosis, which is produced by
several green plants, fungi, and a Streptomyces sp.
MAURICE WELSCH
carboxyphenazine (or griseolutic acid), the griseoluteins A and Β, which
are 9-methoxy-l-carboxyphenazines bearing, respectively, in position 6,
the side chain:
- CH 2 —Ο—CO—CH 2 OH
and
—CH 2 —O—CHOH—CH 2 OH
It should be stressed that, despite the great resemblance of the griseoluteins, only slight cross-resistance is observed between the two antibiotics, and also that, despite the similarity of 1,6-dihydroxyphenazine
and iodinin, the former is specifically antifungal whereas the latter is
antibacterial.
A relation with the shikimic acid route is also probable for the
biosynthesis of the quinoxaline moiety (LXXXI) of antibiotics of the
echinomycin (LX) family and for the quinoline nucleus (LXXXII)
common to the pyo compounds of Pseudomonas aeruginosa. They include
derivatives of 4-oxyquinoline [e.g., 2-n-heptyl, 2-n-nonyl (and their Noxides), 2-n-A
1
-nonenyl 2-n-undecyl-N-oxide] and the 2-n-heptyl-3-oxy4-quinolone. These compounds may arise from the combination of
anthranilic acid with a fatty acid followed by, first, oxidative decarboxylation, and next, reduction. The possibility of direct production from
tryptophan, via kynurenine, has however not been ruled out.
According to Chambers et al. (242), the C 6 -C 3 coumarin moiety of
novobiocin (XVI), as well as the C 6 -Ci fragment to which it is linked
by an amide bond, originate from tyrosine. The cinnamic acid moiety
which, in homomycin (IX) and related antibiotics, is bound to an amino
sugar by an amide linkage, is also likely to be formed via the shikimic
acid pathway, and so is the p-aminobenzoic acid of the amicetin group
of antibiotics (XV).
Little is known of the biosynthesis of chloramphenicol (LXXXIII) by
Streptomyces venezuehe. Contrary to expectation, C
14
-labeled p-nitrophenylserinol and dichloroacetic acid were found not to be incorporated
into its molecule. The presence of the phenylpropane skeleton, however,
suggests its relation to the common aromatic amino acids and the
probability of its origin via the shikimic acid pathway.
The occurrence, in chloramphenicol, of the dichloroacetyl and aryl
nitro groups are rather unusual features for a natural product. The latter,
however, is also found in aureothin (LXXXIV) a by product found in
the cultures of aureothricin-producing S. thioluteus. Α nitro group is
also present in azomycin (LXXXV), a heterocyclic antibiotic produced
by Nocardia mesenterica and Streptomyces eurocidicus, and in the aliphatic antibiotic bovinocidin, N0 2 —CH 2 —CH 2 —COOH, a substance,
weakly active against Mycobactenum tuberculosis, which is produced by
several green plants, fungi, and a Streptomyces sp.