Crystal structures of chiral 2-[bis-(2-chloro-eth-yl)amino]-1,3,2-oxaza-phospho-lidin-2-one derivatives for the absolute configuration at phospho-rus.

ABSTRACT: 'Nitro-gen mustard' bis-(2-chloro-eth-yl)amine derivatives (2R,4S,5R)- and (2S,4S,5R)-2-[bis-(2-chloro-eth-yl)amino]-3,4-dimethyl-5-phenyl-1,3,2-oxaza-phos-pho-lidin-2-one (2a and 2b, respectively), C₁₄H₂₁Cl₂N₂O₂P, and (2R,4R)- and (2S,4R)-2-[bis-(2-chloro-eth-yl)amino]-4-isobutyl-1,3,2-oxaza-phospho-lidin-2-one (3a and 3b, respectively), C₁₀H₂₁Cl₂N₂O₂P, were synthesized as a mixture of diastereomers through a 1:1 reaction of enanti-omerically pure chiral amino alcohols with bis-(2-chloro-eth-yl)phospho-ramidic dichloride. Flash column chromatography yielded diastereomerically pure products, as supported by ³¹P NMR. The crystal structures of 2b and 3b were obtained to determine their absolute configuration at phospho-rus, and ³¹P NMR chemical shift trends are proposed based on the spatial relationship of the bis-(2-chloro-eth-yl)amine moiety and the chiral substituent of the amino alcohol. Oxaza-phospho-lidinones were observed to have a more downfield ³¹P NMR chemical shift when the aforementioned substituents are in a syn configuration and vice versa for when they are anti.

SUBMITTER: Rohde LN 

PROVIDER: S-EPMC6127709 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature