Open AccessSolid-Phase Synthesis of ɤ-Lactone and 1,2-Oxazine Derivatives and Their Efficient Chiral Analysis
Author(s) -
Soňa Křupková,
Gonzalo Pazos Aguete,
Leona Kocmanova,
Tereza Volná,
Martin Grepl,
Lucie Nováková,
Marvin J. Miller,
Jan Hlaváč
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0166558
Subject(s) - dihydroxylation , regioselectivity , chemistry , stereoselectivity , bond cleavage , double bond , sorbic acid , high performance liquid chromatography , carboxylic acid , organic chemistry , combinatorial chemistry , stereochemistry , enantioselective synthesis , catalysis
Derivatives of 3-methyl-3,6-dihydro-2 H -1,2-oxazine-6-carboxylic acid prepared by regioselective hetero Diels-Alder reaction of arylnitroso compounds with sorbic acid were used for solid-phase synthesis of a library of derivatives that included modification of carboxylic group, dihydroxylation of double bond and cleavage of N-O bond. Derivatives of 2,3,4-trihydroxyhexanoic acid obtained from 3,6-dihydro-2 H -1,2-oxazines after double bond dihydroxylation and N-O cleavage were used for simple and stereoselective formation of chiral lactones derived from 3,4-dihydroxydihydrofuran-2(3 H )-one. The final compounds obtained as a mixture of stereoisomers were analyzed with use of chiral HPLC and SFC. HPLC analyses were not successful for all derivatives or required lengthy chromatography. On the other hand SFC afforded much shorter analyses and was effective for all studied derivatives. The method of synthesis and analysis is thus suitable for future study of stereoselective synthesis of lactones and other derivatives from single oxazine derivatives and application of high-throughput synthesis on solid-support and combinatorial chemistry.