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Digital archive of theses discussed at the University of Pisa


Thesis etd-02192010-184518

Thesis type
Tesi di dottorato di ricerca
Thesis title
Synthesis of N-Cbz Imino glycal-derived allyl epoxides and aziridines and of 2-alkoxy-D-galactal-derived allyl epoxide. Regio- and stereoselectivity in nucleophilic addition reactions.
Academic discipline
Course of study
tutor Prof. Crotti, Paolo
  • 3-deoxy sugar
  • addition reactions
  • allyl-aziridine
  • allyl-oxirane
  • azasugars
  • glycal
  • glycosylation
  • imino glycal
  • iminosugars
Graduation session start date
Release date
The present thesis deals with the synthesis of new azasugars precursors and/or derivatives, as the diastereoisomeric iminoglycal-derived allyl epoxides and activated aziridines, and corresponding addition products, and with the synthesis of the new allyl epoxide derived from 2-OMEM-substituted-D-galactal, as a precursor of alkyl 3-deoxy-O-glycosides and corresponding conjugated 3-oxo derivatives. In particular, as for the azasugars precursor, the diastereoisomeric 6-OBn-substituted epoxides 4.1α and 4.1β, derived from D,L-N-Cbz-imino allal and –imino galactal, respectively and the corresponding 6-deoxy-epoxides 5.1α and 5.1β and N-nosyl aziridines 6.1α and 6.1β, not previously described activated imino glycal derivatives, were synthesized in a completely regio- and stereoselective fashion in which the initial construction of the imino glycal moiety was performed by adopting the Comin’s approach based on the addition of the appropriate organometallic reagent to the N-Cbz pyridinium chloride. Our interest in allyl epoxides 4.1α, 4.1β, 5.1α, 5.1β and allyl N-nosyl aziridines 6.1α-6.1β derived from our intention to synthesize azasugars and corresponding derivatives, in view of their biological properties, by means of imino glycals. A further interest derived also from an examination of relevant literature, which indicated that appropriately substituted imino glycal systems react with nucleophiles showing a large or complete facial selectivity dependent on the nature of the nucleophilic attack, with the exclusive or almost exclusive formation of the corresponding β-anomer (product-dependent selectivity). In this framework, it appeared interesting to check whether the facial selectivity observed in the nucleophilic addition reactions to imino glycal-derived epoxides and aziridines 4.1α-6.1β was independent of the nature of the nucleophilic attack and dependent on the configuration of the heterocyclic system (substrate-dependent selectivity). 6-OBn-Substituted epoxides 4.1α-4.1β, 6-deoxy epoxides 5.1α-5.1β and N-nosyl aziridines 6.1α-6.1β turned out to be excellent glycosyl donors and able to glycosylate alcohols and partially protected monosaccharides in a completely 1,4-regio- and stereoselective fashion with the exclusive formation of corresponding alkyl 2,3-unsaturated-O-glycosides with the same configuration (α or β) as the starting epoxide or aziridines (α or β) in a directly substrate-dependent glycosylation process. In this framework, the use of N-nosyl aziridines 6.1α and 6.1α allowed the regio- and stereoselective insertion of a free amino group at C(4) of an azapyranoside system. The transformation of the obtained alkyl 2,3-unsaturated-O-glycosides into corresponding azapyranosides was also achieved and subsequent transformation into azasugars realized in some cases.
2-OMEM-substituted D-galactal-derived epoxide 7.5β-OMEM, regio- and stereoselectively prepared through an original synthetic process, turned out to be an excellent glycosyl donor and alcohols were glycosylated by a corresponding substrate-dependent selectivity. Subsequent deprotection of the –OMEM functionality, carried out by an original and mild protocol, led to the regioselective synthesis of 2-oxo-2,3-dideoxy-O-glycosides and corresponding conjugated unsaturated enone system useful for further functionalizations.