“…All of the lipases tested hydrolyzed the (2 S, 3 R ) enantiomer of ester 7 . Identical results were obtained by Clark et al for the hydrolysis of the corresponding ethyl ester: with immobilized protease from Streptomyces griseus (2 S, 3 R )- 4 was obtained with 95% ee. With a best E -value of 48 the maximal reachable ee for (2 S, 3 R )- 4 will be 96%.…”
Section: Resultssupporting
confidence: 81%
“…No efforts at optimization and scale-up of this reaction were made (Scheme ). The enantiopure (1 R, 2 R ) amino diol 3 , obtained in 73% yield from 4 , can be transferred into thiamphenicol and florfenicol by methods described in the literature. − 8 …”
Section: Resultsmentioning
confidence: 99%
“…More recently, researchers at Celgene described the use of an aldolase to promote the retro-aldol reaction of the (2 R, 3 S ) enantiomer of racemic threo -3-[4-(methylthio)phenyl]serine ( 4 ), leaving the desired (2 S, 3 R ) enantiomer of 4 . Other enzymatic resolution processes are described by Clark et al in which additional reaction steps are necessary. , Various asymmetric syntheses for florfenicol and thiamphenicol 10 and synthesis from chloramphenicol 11 have been described, but most of these methods lack practical applicability on a large scale.…”
Enantiomerically pure 4-methylthio- and 4-methylsulfonyl-substituted (2S,3R)-3-phenylserines are prepared
by enzymatic
resolution of the corresponding racemic threo amides using
the
amidase from Ochrobactrum anthropi NCIMB 40321.
The
unwanted (2R,3S) enantiomers of the amides are
separated from
the enantiopure amino acids and easily racemized after
Schiff
base formation with the corresponding 4-(methylthio)- and
4-(methylsulfonyl)benzaldehyde. The racemization can
be
combined with the preparation of the racemic amides by
aldol
reaction under crystallization conditions to yield only the
threo
isomers. Enantiopure
(2S,3R)-3-[4-(methylthio)phenyl]serine
and
(2S,3R)-3-[4-(methylsulfonyl)phenyl]serine
are thus obtained in 78% and 62% overall yields starting from the
corresponding substituted benzaldehydes.
(2S,3R)-3-[4-(Methylthio)phenyl]serine is reduced to
(1R,2R)-2-amino-1-[4-(methylthio)phenyl]propane-1,3-diol with
NaBH4/H2SO4 and can
be
used for the synthesis of thiamphenicol and florfenicol.
“…All of the lipases tested hydrolyzed the (2 S, 3 R ) enantiomer of ester 7 . Identical results were obtained by Clark et al for the hydrolysis of the corresponding ethyl ester: with immobilized protease from Streptomyces griseus (2 S, 3 R )- 4 was obtained with 95% ee. With a best E -value of 48 the maximal reachable ee for (2 S, 3 R )- 4 will be 96%.…”
Section: Resultssupporting
confidence: 81%
“…No efforts at optimization and scale-up of this reaction were made (Scheme ). The enantiopure (1 R, 2 R ) amino diol 3 , obtained in 73% yield from 4 , can be transferred into thiamphenicol and florfenicol by methods described in the literature. − 8 …”
Section: Resultsmentioning
confidence: 99%
“…More recently, researchers at Celgene described the use of an aldolase to promote the retro-aldol reaction of the (2 R, 3 S ) enantiomer of racemic threo -3-[4-(methylthio)phenyl]serine ( 4 ), leaving the desired (2 S, 3 R ) enantiomer of 4 . Other enzymatic resolution processes are described by Clark et al in which additional reaction steps are necessary. , Various asymmetric syntheses for florfenicol and thiamphenicol 10 and synthesis from chloramphenicol 11 have been described, but most of these methods lack practical applicability on a large scale.…”
Enantiomerically pure 4-methylthio- and 4-methylsulfonyl-substituted (2S,3R)-3-phenylserines are prepared
by enzymatic
resolution of the corresponding racemic threo amides using
the
amidase from Ochrobactrum anthropi NCIMB 40321.
The
unwanted (2R,3S) enantiomers of the amides are
separated from
the enantiopure amino acids and easily racemized after
Schiff
base formation with the corresponding 4-(methylthio)- and
4-(methylsulfonyl)benzaldehyde. The racemization can
be
combined with the preparation of the racemic amides by
aldol
reaction under crystallization conditions to yield only the
threo
isomers. Enantiopure
(2S,3R)-3-[4-(methylthio)phenyl]serine
and
(2S,3R)-3-[4-(methylsulfonyl)phenyl]serine
are thus obtained in 78% and 62% overall yields starting from the
corresponding substituted benzaldehydes.
(2S,3R)-3-[4-(Methylthio)phenyl]serine is reduced to
(1R,2R)-2-amino-1-[4-(methylthio)phenyl]propane-1,3-diol with
NaBH4/H2SO4 and can
be
used for the synthesis of thiamphenicol and florfenicol.
“…In the literature, several approaches for the synthesis of florfenicol have been reported . But none of the reported procedures could be adopted as such because our requirement was for the [ S ‐methyl‐ 14 C]‐florfenicol.…”
Section: Resultsmentioning
confidence: 99%
“…In the literature, several approaches for the synthesis of florfenicol have been reported. 3,4,[6][7][8][9][10][11][12][13][14][15][16] But none of the reported procedures could be adopted as such because our requirement was for the [S-methyl-14 C]-florfenicol. Introduction of the radioisotopic label at the latest possible stage of the synthesis has generally been recognized as ideal on consideration of yield, cost, risk, and so on.…”
In this paper is reported a novel reaction scheme for the no-carrier-added submicromolar scale radiosynthesis of [S-methyl-(14)C]-florfenicol that has been newly designed, developed and employed by us successfully. The [(14)C]-product was obtained in an overall radiochemical yield of 30% based on [(14)C]-methyl iodide taken for the reaction with a radiochemical purity of more than 96%. The specific activity of the product was ~50 mCi (1.85 GBq)/mmol. Chlorosulfonation of compound I was followed by sodium salt formation in situ and it was succeeded by the introduction of [(14)C]-methyl group by coupling with [(14)C]-CH3 I. Subsequently, the oxazolidin-2-one protecting group was opened up by a reaction with sulfuric acid in dioxane and later, the amino group was dichloroacetylated with methyl-2,2-dichloroacetate in triethylamine to obtain [S-methyl-(14)C]-florfenicol.
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