Synthesis of polyhydroxylated cyclopentanes from bromodeoxyaldonolactones.

Anne Marie Horneman

    Research output: Book/ReportBook

    Abstract

    The aim of this work has been the preparation of polyhydroxy carbocycles from bromodeoxyaldonolactones. Intramolecular radical cyclisation of alfa,beta-unsaturated lactones was shown to be a good method for this purpose.Starting from mono- and dibromo-heptonolactones a series of 7-bromo-7-deoxy-hept-2-enono-1,4-lactones were prepared in either two or three steps. 7-Bromo-5,6-di-O-acetyl-2,3,7-trideoxy-D-arabino-hept-2-enono-1,4- lactone (3) and 7-bromo-5,6-di-O-acetyl-2,3,7-trideoxy-D-lyxo-hept-2-enono-1,4-lac tone (6) were prepared by NaHSO3-induced beta-bromo-acetoxy elimination starting from 2,7-dibromo-2,7-dideoxy-D-glycero-D-ido-heptono-1,4-lactone (1) and 2,7-dibromo-2,7-dideoxy-D-glycero-L-gluco-heptono-1,4-lactone (4) respectively.Five alfa,beta-unsaturated heptonolactones possessing an acetoxy or an azido substituent at C-2 were prepared by base induced beta-hydro-acetoxy-elimination. The beta-hydro-acetoxy-eliminations were followed by isomerisation at C-4, which could not be avoided. Thus 2-O-acetyl-7-bromo-3,7-dideoxy-5,6-O-isopropylidene-D-arabino-hept -2-enono-1,4-lactone (24) and 2-O-acetyl-7-bromo-3,7-dideoxy-5,6-O-isopropylidene-D-ribo-hept-2- enono-1,4-lactone (25)were prepared starting from 7-bromo-7-deoxy-D-glycero-D-galacto-heptono-1,4-lactone (19), 2-O-acetyl-7-bromo-3,7-dideoxy-D-xylo-hept-2-enono-1,4-lactone (64) and 2-O-acetyl-7-bromo-3,7-dideoxy-D-lyxo-hept-2-enono-1,4-lactone (65) were prepared from 7-bromo-7-deoxy-D-glycero-L-galacto-heptono-1,4-lactone (59), and 2-azido-7-bromo-5,6-di-O-acetyl-2,3,7-trideoxy-D-arabino-hept-2-en ono-1,4-lactone (38) was prepared starting from 1. Additionally, compound 3 was converted into the C-4 epimer 35 by base catalysed epimerisation.The eight 7-bromo-7-deoxy-hept-2-enono-1,4-lactones were submitted to tributyltin hydride promoted radical cyclisations to give bicyclic cyclopentane derivatives. The cyclisations gave rise to the formation of one or two new chiral centres, depending on the substitution pattern of the starting compound. The reactions occurred with high regio and stereoselectivity and thus the cyclisation products 14, 15, 31, 32, 36, 44, 69 and 71 were isolated in yields of 80%-90%.The lactone moieties of the bicyclic products were reduced to hydroxyl groups. The polyhydroxy cyclopentanes obtained by reduction can be seen as carbocyclic analogues of furanoses. Thus the following carbafuranoses were prepared: 5-Deoxycarba-alfa-L-xylo-hexofuranose (78), 5-deoxycarba-alfa-L-lyxo-hexofuranose (80), 5-deoxycarba-beta-D-lyxo-hexofuranose (82), carba-beta-D-glucofuranose (83), carba-alfa-L-mannofuranose (84), carba-alfa-L-glucofuranose (86), carba, beta-D-mannofuranose (88) carba-alfa-L-xylofuranose (90), carba-beta-D-lyxofuranose (92) and 5-amino-5-deoxycarba-alfa-L-glucofuranose hydrochloride (94). These carbasugars showed only moderate inhibitory effect towards alfa and beta glucosidase, alfa and beta mannosidase, and alfa galactosidase.
    Original languageEnglish
    Place of PublicationLyngby
    PublisherTechnical University of Denmark
    Number of pages140
    Publication statusPublished - 1996

    Cite this

    Horneman, A. M. (1996). Synthesis of polyhydroxylated cyclopentanes from bromodeoxyaldonolactones. Technical University of Denmark.