Approaches towards the total synthesis of the ephedradine alkaloids
Approaches towards the total synthesis of the ephedradine alkaloids
A general procedure for the preparation of substituted trans 2,3-dihydro-5-formyl-3-methoxy carbonyl benzo[b]furans by cationic cyclisation of methyl-2-[2-benzyloxy-5-(dimethoxymethyl)phenyl]-3-aryl-3-hydroxypropionate derivatives has been developed. The procedure has been employed in the preparation of the four northern dihydrobenzo[b]furan segments of the ephedradine alkaloids. Studies directed towards the enantioselective synthesis of the dihydrobenzofuran moieties of the ephedradines A-D are described. Thus, (4S)-(-)-3-[(2S,3S)-2-(2-benzyloxyphenyl)-3-(4-benzyloxyphenyl)-3-hydroxy-1-oxopropyl]-4-isopropyl-2-oxazolidione (197) was cyclised to give (4S)-(+)-3-[(2S,3S)-2,3-dihydro-2-(4-hydroxyphenyl)benzo[b]furan-3-ylcarbonyl]-4-isopropyl-2-oxazolidinone (198). Subsequent transformation of oxazolidinone (198) gave the chiral derivatives (+)-(2S,3S)-2,3-dihydro-3-methoxycarbonyl-2-(4-methoxyphenyl)benzo[b]furan (200) and (+)-(2S,3R)-2,3-dihydro-3-hydroxymethyl-2-(4-methoxyphenyl)benzo[b]furan (201). (4R, 2R, 3R) - (198 was readily prepared from (4R, 2R 3R) - (197) in an analogous fashion. The preparation of the novel triprotected spermine unit (213) has been achieved and conditions obtained for the efficient coupling of (213) to the dihydrobenzo[b]furan moieties to afford N-(tert-butoxycarbonyl)-11-cyano-9-[2R,3R)-2,3-dihydro-5-formyl-2-(4-methoxyphenyl)benzo[b]furan-3-ylcarbonyl]-4-(p-toluenesulphonyl)-4,9-diazaundecyl-1-amine (227) and the 7-methoxy derivative (224). Introduction of the C16-17 unit was investigated and the formation of the ephedradine `skeleton' attempted using macrocyclisation reactions. The preparation and intramolecular transamidation reaction of 5-(4-aminobutyl)-4-oxo-2-phenyl-1,5-diazacyclooctane (267) was investigated as an approach to the formation of spermine containing polyaminolactams. (D80180)
University of Southampton
1987
Humphrey, Guy Rowland
(1987)
Approaches towards the total synthesis of the ephedradine alkaloids.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
A general procedure for the preparation of substituted trans 2,3-dihydro-5-formyl-3-methoxy carbonyl benzo[b]furans by cationic cyclisation of methyl-2-[2-benzyloxy-5-(dimethoxymethyl)phenyl]-3-aryl-3-hydroxypropionate derivatives has been developed. The procedure has been employed in the preparation of the four northern dihydrobenzo[b]furan segments of the ephedradine alkaloids. Studies directed towards the enantioselective synthesis of the dihydrobenzofuran moieties of the ephedradines A-D are described. Thus, (4S)-(-)-3-[(2S,3S)-2-(2-benzyloxyphenyl)-3-(4-benzyloxyphenyl)-3-hydroxy-1-oxopropyl]-4-isopropyl-2-oxazolidione (197) was cyclised to give (4S)-(+)-3-[(2S,3S)-2,3-dihydro-2-(4-hydroxyphenyl)benzo[b]furan-3-ylcarbonyl]-4-isopropyl-2-oxazolidinone (198). Subsequent transformation of oxazolidinone (198) gave the chiral derivatives (+)-(2S,3S)-2,3-dihydro-3-methoxycarbonyl-2-(4-methoxyphenyl)benzo[b]furan (200) and (+)-(2S,3R)-2,3-dihydro-3-hydroxymethyl-2-(4-methoxyphenyl)benzo[b]furan (201). (4R, 2R, 3R) - (198 was readily prepared from (4R, 2R 3R) - (197) in an analogous fashion. The preparation of the novel triprotected spermine unit (213) has been achieved and conditions obtained for the efficient coupling of (213) to the dihydrobenzo[b]furan moieties to afford N-(tert-butoxycarbonyl)-11-cyano-9-[2R,3R)-2,3-dihydro-5-formyl-2-(4-methoxyphenyl)benzo[b]furan-3-ylcarbonyl]-4-(p-toluenesulphonyl)-4,9-diazaundecyl-1-amine (227) and the 7-methoxy derivative (224). Introduction of the C16-17 unit was investigated and the formation of the ephedradine `skeleton' attempted using macrocyclisation reactions. The preparation and intramolecular transamidation reaction of 5-(4-aminobutyl)-4-oxo-2-phenyl-1,5-diazacyclooctane (267) was investigated as an approach to the formation of spermine containing polyaminolactams. (D80180)
This record has no associated files available for download.
More information
Published date: 1987
Identifiers
Local EPrints ID: 461565
URI: http://eprints.soton.ac.uk/id/eprint/461565
PURE UUID: a7deec73-2660-4514-89ae-8f2de6efa3b3
Catalogue record
Date deposited: 04 Jul 2022 18:50
Last modified: 04 Jul 2022 18:50
Export record
Contributors
Author:
Guy Rowland Humphrey
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics