David J. S. Tsai

Determination of enantiomers in a synthetic argininal peptide using capillary zone electrophoresis and high-performance liquid chromatography.

SCH 201781 is a synthetic argininal peptide containing two chiral centers and an aromatic sulfonamide group. It can exist as four reversible forms, the aldehyde, the hydrate, and two diastereomeric aminals. Capillary zone electrophoresis (CZE) and reversed-phase high-performance liquid chromatographic (HPLC) methods were developed to separate and quantitate the enantiomers in SCH 201781. Comparable results were obtained using both methods. The CZE method uses direct injection, while the HPLC method requires a precolumn derivatization and is more time consuming. The CZE method provides superior sensitivity to the HPLC method. Both methods were shown to be precise and reproducible.

STRUCTURAL DETERMINATION OF TWO ISOMERS OF BETAMETHASONE BY NMR SPECTROSCOPY

Two isomers of betamethasone 9α‐fluoro‐11β,17α,21‐trihydroxy‐16β‐methylpregna‐1,4‐diene‐3,20‐dione (1), were isolated from the mother liquor of a manufacturing process and were characterized by NMR spectroscopy. They were identified as 8α‐fluoro‐11β,17α,21‐trihydroxy‐16β‐methyl‐9β‐pregna‐1,4‐diene‐3,20‐dione (2) and 14β‐fluoro‐11β,17α,21‐trihydroxy‐16β‐methyl‐8α,9β‐pregna‐1,4‐diene‐3,20‐dione (3). The stereochemistries of 2 and 3 were assigned on the basis of proton–proton and proton–fluorine NOE experiments. The structure of the former was confirmed by x‐ray crystallographic analysis.