5. ONIUM COMPOUNDS
207
The presence of the sulfonium configuration, as is well known, confers on a compound an additional center of optical activity, and
stereoisomers of sulfonium compounds have been separated by classical
chemical procedures (131, 132). Synthetic S-adenosylmethionine,
whether prepared by chemical methylation of S-adenosylhomocysteine
(133) or by condensation of 5'-methylthioadenosine with 2-amino-4bromobutyric acid would be expected to be a mixture of diastereoisomerides, while it could be expected that the natural compound would
be optically homogeneous. Recently both sulfonium diastereoisomers of
S-adenosyl-L-methionine have been prepared by different enzymatic
procedures, based on the fact that the synthetic compound differs from
the natural compounds in that it is utilized only to 50% in the enzymatic
methylation of guanidinoacetic acid (whereas under similar conditions
natural S-adenosylmethionine is utilized to 90-100%). These findings
suggested that one of the two stereoisomers of S-adenosyl-L-methionine
NH 2
L 1 >-H
^NA N /
H
CH—CH(OH)—CH(OH)—CH—CH 2 —S—CH 2 -CH 2 —CH(NH 2 )—COOI
O
1
CH 3
FIG. 6. S-Adenosylmethionine.
might be inactive as a methyl donor in this and possibly other enzymatic systems. The optical rotation of the two sulfonium diastereoisomers has been determined and compared to that of the synthetic compound (134). It was found that the optical rotation of samples of
S-adenosyl-L-methionine prepared by the chemical methylation of
adenosylhomocysteine was f [«] 589 o
240 ( + ) 52°}; this value is significantly different from that of S-adenosylmethionine formed by the
methionine activating enzymes of liver and yeast which gave identical
values of {[a] 5 89o
24 approx. (-f-)48°}. Finally the optical rotation of
the epimeric sulfonium isomer of S-adenosyl-L-methionine was
{[a]r,89o
24
° ( + ) 57°}. This isomer,* which may be designated as
* In considering the four diastereoisomerides possible in S-adenosylmethionine,
it will be convenient to use the conventional designations D- and L- to describe the
configuration about the 2-carbon atom, while using the symbols (-f) and ( —) to
indicate the contribution of the sulfonium group to the rotation of the whole
molecule. The completely racemic compound will be described as ( ±) S-adenosylDL-methionine and the natural, or enzymatically formed compound as ( —)Sadenosyl-L-methionine.
207
The presence of the sulfonium configuration, as is well known, confers on a compound an additional center of optical activity, and
stereoisomers of sulfonium compounds have been separated by classical
chemical procedures (131, 132). Synthetic S-adenosylmethionine,
whether prepared by chemical methylation of S-adenosylhomocysteine
(133) or by condensation of 5'-methylthioadenosine with 2-amino-4bromobutyric acid would be expected to be a mixture of diastereoisomerides, while it could be expected that the natural compound would
be optically homogeneous. Recently both sulfonium diastereoisomers of
S-adenosyl-L-methionine have been prepared by different enzymatic
procedures, based on the fact that the synthetic compound differs from
the natural compounds in that it is utilized only to 50% in the enzymatic
methylation of guanidinoacetic acid (whereas under similar conditions
natural S-adenosylmethionine is utilized to 90-100%). These findings
suggested that one of the two stereoisomers of S-adenosyl-L-methionine
NH 2
L 1 >-H
^NA N /
H
CH—CH(OH)—CH(OH)—CH—CH 2 —S—CH 2 -CH 2 —CH(NH 2 )—COOI
O
1
CH 3
FIG. 6. S-Adenosylmethionine.
might be inactive as a methyl donor in this and possibly other enzymatic systems. The optical rotation of the two sulfonium diastereoisomers has been determined and compared to that of the synthetic compound (134). It was found that the optical rotation of samples of
S-adenosyl-L-methionine prepared by the chemical methylation of
adenosylhomocysteine was f [«] 589 o
240 ( + ) 52°}; this value is significantly different from that of S-adenosylmethionine formed by the
methionine activating enzymes of liver and yeast which gave identical
values of {[a] 5 89o
24 approx. (-f-)48°}. Finally the optical rotation of
the epimeric sulfonium isomer of S-adenosyl-L-methionine was
{[a]r,89o
24
° ( + ) 57°}. This isomer,* which may be designated as
* In considering the four diastereoisomerides possible in S-adenosylmethionine,
it will be convenient to use the conventional designations D- and L- to describe the
configuration about the 2-carbon atom, while using the symbols (-f) and ( —) to
indicate the contribution of the sulfonium group to the rotation of the whole
molecule. The completely racemic compound will be described as ( ±) S-adenosylDL-methionine and the natural, or enzymatically formed compound as ( —)Sadenosyl-L-methionine.