Resolution of chiral drugs by liquid chromatography based upon diastereomer formation with chiral derivatization reagents

Separating chiral isomers of amphetamine and methamphetamine using chemical derivatization and differential mobility spectrometry

“…However, since DMS has previously been used to separate diastereomers, 23 , 35 we pursued a chemical derivatization approach to generate diastereomers from the target enantiomer analytes using S‐TPC 8 , 9 as the reagent. Aside from these previous DMS studies, we have recently separated isomeric species using DMS that exhibited different physicochemical properties 39 , 48 ; since diastereomers typically exhibit different physicochemical properties from one another, 70 , 71 we hypothesized that DMS separation of the TPC‐AMP synthesized diastereomers should be achievable.…”

Separating chiral isomers of amphetamine and methamphetamine using chemical derivatization and differential mobility spectrometry

“…However, since DMS has previously been used to separate diastereomers, 23 , 35 we pursued a chemical derivatization approach to generate diastereomers from the target enantiomer analytes using S‐TPC 8 , 9 as the reagent. Aside from these previous DMS studies, we have recently separated isomeric species using DMS that exhibited different physicochemical properties 39 , 48 ; since diastereomers typically exhibit different physicochemical properties from one another, 70 , 71 we hypothesized that DMS separation of the TPC‐AMP synthesized diastereomers should be achievable.…”

Synthesis and Characterization of Four Diastereomers of Monorhamnolipids

“…Unfortunately, these approaches are not readily amenable to production of these materials at scale, as they are labor intensive (>18 steps per diastereomer) and use expensive reagents, dangerous procedures, and low yielding reactions. Here, we report a solution phase methodology in which a long shelf life, air and moisture stable peracetylated rhamnose donor can be activated in the presence of a minimally competent Lewis acid , to produce a racemic mixture of the lipid acceptor that can be resolved in a flash preparative silica column by means of enantiomer-to-diastereomer conversion − after stereocontrolled glycosylation. The pure free acid diastereomers are esterified with the second lipid unit to render a new mixture of diastereomers that is separable as free acids by conventional flash column chromatography.…”

High‐performance liquid chromatographic enantioseparation of (RS)‐bupropion using isothiocyanate‐based chiral derivatizing reagents

“…Most of the reactions for enantioseparation of chiral amines are based on the formation of amide, carbamate, urea and thiourea derivatives. The thiourea diastereomers, formed by reaction with isothiocyanate‐based CDR, are readily separated on a reversed‐phase (RP) C 18 column in spite of the large distance between the two chiral centers (in the diastereomer; Toyo'oka, ). In the present study, reaction of BUP with isothiocyanate‐based CDRs yielded thiourea diastereomers.…”

Separating chiral isomers of amphetamine and methamphetamine using chemical derivatization and differential mobility spectrometry

“…However, since DMS has previously been used to separate diastereomers, 23 , 35 we pursued a chemical derivatization approach to generate diastereomers from the target enantiomer analytes using S‐TPC 8 , 9 as the reagent. Aside from these previous DMS studies, we have recently separated isomeric species using DMS that exhibited different physicochemical properties 39 , 48 ; since diastereomers typically exhibit different physicochemical properties from one another, 70 , 71 we hypothesized that DMS separation of the TPC‐AMP synthesized diastereomers should be achievable.…”

Synthesis and Characterization of Four Diastereomers of Monorhamnolipids

“…Unfortunately, these approaches are not readily amenable to production of these materials at scale, as they are labor intensive (>18 steps per diastereomer) and use expensive reagents, dangerous procedures, and low yielding reactions. Here, we report a solution phase methodology in which a long shelf life, air and moisture stable peracetylated rhamnose donor can be activated in the presence of a minimally competent Lewis acid , to produce a racemic mixture of the lipid acceptor that can be resolved in a flash preparative silica column by means of enantiomer-to-diastereomer conversion − after stereocontrolled glycosylation. The pure free acid diastereomers are esterified with the second lipid unit to render a new mixture of diastereomers that is separable as free acids by conventional flash column chromatography.…”

High‐performance liquid chromatographic enantioseparation of (RS)‐bupropion using isothiocyanate‐based chiral derivatizing reagents

“…Most of the reactions for enantioseparation of chiral amines are based on the formation of amide, carbamate, urea and thiourea derivatives. The thiourea diastereomers, formed by reaction with isothiocyanate‐based CDR, are readily separated on a reversed‐phase (RP) C 18 column in spite of the large distance between the two chiral centers (in the diastereomer; Toyo'oka, ). In the present study, reaction of BUP with isothiocyanate‐based CDRs yielded thiourea diastereomers.…”

Separating chiral isomers of amphetamine and methamphetamine using chemical derivatization and differential mobility spectrometry

“…However, since DMS has previously been used to separate diastereomers, 23 , 35 we pursued a chemical derivatization approach to generate diastereomers from the target enantiomer analytes using S‐TPC 8 , 9 as the reagent. Aside from these previous DMS studies, we have recently separated isomeric species using DMS that exhibited different physicochemical properties 39 , 48 ; since diastereomers typically exhibit different physicochemical properties from one another, 70 , 71 we hypothesized that DMS separation of the TPC‐AMP synthesized diastereomers should be achievable.…”

Synthesis and Characterization of Four Diastereomers of Monorhamnolipids

“…Unfortunately, these approaches are not readily amenable to production of these materials at scale, as they are labor intensive (>18 steps per diastereomer) and use expensive reagents, dangerous procedures, and low yielding reactions. Here, we report a solution phase methodology in which a long shelf life, air and moisture stable peracetylated rhamnose donor can be activated in the presence of a minimally competent Lewis acid , to produce a racemic mixture of the lipid acceptor that can be resolved in a flash preparative silica column by means of enantiomer-to-diastereomer conversion − after stereocontrolled glycosylation. The pure free acid diastereomers are esterified with the second lipid unit to render a new mixture of diastereomers that is separable as free acids by conventional flash column chromatography.…”

High‐performance liquid chromatographic enantioseparation of (RS)‐bupropion using isothiocyanate‐based chiral derivatizing reagents

“…Most of the reactions for enantioseparation of chiral amines are based on the formation of amide, carbamate, urea and thiourea derivatives. The thiourea diastereomers, formed by reaction with isothiocyanate‐based CDR, are readily separated on a reversed‐phase (RP) C 18 column in spite of the large distance between the two chiral centers (in the diastereomer; Toyo'oka, ). In the present study, reaction of BUP with isothiocyanate‐based CDRs yielded thiourea diastereomers.…”