{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:41:45Z","timestamp":1787071305566,"version":"build-2736575974"},"reference-count":48,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2020,10,2]],"date-time":"2020-10-02T00:00:00Z","timestamp":1601596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cassa di Risparmio di Pistoia e Pescia","award":["Bando Giovani@Ricerca scientifica 2017"],"award-info":[{"award-number":["Bando Giovani@Ricerca scientifica 2017"]}]},{"DOI":"10.13039\/501100015694","name":"Fondazione CR Firenze","doi-asserted-by":"publisher","award":["Bando congiunto per il finanziamento di progetti competitivi sulle malattie neurodegenerative. Project: A multidisciplinary approach to target Parkinson\u2019s disease in Gaucher related population, Acronym: MuTaParGa"],"award-info":[{"award-number":["Bando congiunto per il finanziamento di progetti competitivi sulle malattie neurodegenerative. Project: A multidisciplinary approach to target Parkinson\u2019s disease in Gaucher related population, Acronym: MuTaParGa"]}],"id":[{"id":"10.13039\/501100015694","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015694","name":"Fondazione CR Firenze","doi-asserted-by":"publisher","award":["grant N\u00b02018.0942"],"award-info":[{"award-number":["grant N\u00b02018.0942"]}],"id":[{"id":"10.13039\/501100015694","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015694","name":"Fondazione CR Firenze","doi-asserted-by":"publisher","award":["grant number 2017.0734"],"award-info":[{"award-number":["grant number 2017.0734"]}],"id":[{"id":"10.13039\/501100015694","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministerio de Econom\u00eda y Competitividad of Spain","award":["CTQ2016-77270-R"],"award-info":[{"award-number":["CTQ2016-77270-R"]}]},{"name":"Regione Toscana (Bando Salute 2018)","award":["\u201cLate onset Lysosomal Storage Disorders (LSDs) in the differential diagnosis of neurodegenerative diseases: development of new diagnostic procedures and focus on potential pharmacological chaperones (PCs), Acronym: Lysolate"],"award-info":[{"award-number":["\u201cLate onset Lysosomal Storage Disorders (LSDs) in the differential diagnosis of neurodegenerative diseases: development of new diagnostic procedures and focus on potential pharmacological chaperones (PCs), Acronym: Lysolate"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Pharmacological chaperones (PCs) are small compounds able to rescue the activity of mutated lysosomal enzymes when used at subinhibitory concentrations. Nitrogen-containing glycomimetics such as aza- or iminosugars are known to behave as PCs for lysosomal storage disorders (LSDs). As part of our research into lysosomal sphingolipidoses inhibitors and looking in particular for new \u03b2-galactosidase inhibitors, we report the synthesis of a series of alkylated azasugars with a relative \u201call-cis\u201d configuration at the hydroxy\/amine-substituted stereocenters. The novel compounds were synthesized from a common carbohydrate-derived piperidinone intermediate 8, through reductive amination or alkylation of the derived alcohol. In addition, the reaction of ketone 8 with several lithium acetylides allowed the stereoselective synthesis of new azasugars alkylated at C-3. The activity of the new compounds towards lysosomal \u03b2-galactosidase was negligible, showing that the presence of an alkyl chain in this position is detrimental to inhibitory activity. Interestingly, 9, 10, and 12 behave as good inhibitors of lysosomal \u03b2-glucosidase (GCase) (IC50 = 12, 6.4, and 60 \u00b5M, respectively). When tested on cell lines bearing the Gaucher mutation, they did not impart any enzyme rescue. However, altogether, the data included in this work give interesting hints for the design of novel inhibitors.<\/jats:p>","DOI":"10.3390\/molecules25194526","type":"journal-article","created":{"date-parts":[[2020,10,3]],"date-time":"2020-10-03T07:22:16Z","timestamp":1601709736000},"page":"4526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Synthesis of \u201cAll-Cis\u201d Trihydroxypiperidines from a Carbohydrate-Derived Ketone: Hints for the Design of New \u03b2-Gal and GCase Inhibitors"],"prefix":"10.3390","volume":"25","author":[{"given":"Maria Giulia","family":"Davighi","sequence":"first","affiliation":[{"name":"Department of Chemistry \u201cUgo Schiff\u201d, University of Firenze, via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Clemente","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cUgo Schiff\u201d, University of Firenze, via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8336-383X","authenticated-orcid":false,"given":"Camilla","family":"Matassini","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cUgo Schiff\u201d, University of Firenze, via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2890-8179","authenticated-orcid":false,"given":"Amelia","family":"Morrone","sequence":"additional","affiliation":[{"name":"Paediatric Neurology Unit and Laboratories, Neuroscience Department, Meyer Children\u2019s Hospital and Department of Neurosciences, Pharmacology and Child Health, University of Florence, Viale Pieraccini 24, 50139 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Goti","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cUgo Schiff\u201d, University of Firenze, via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy"},{"name":"Associated with Consorzio Interuniversitario Nazionale di Ricerca in Metodologie e Processi Innovativi di Sintesi (CINMPIS), 70100 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Macarena","family":"Mart\u00ednez-Bail\u00e9n","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Facultad de Qu\u00edmica, Universidad de Sevilla, Garc\u00eda Gonz\u00e1lez 1, E-41012 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6766-4624","authenticated-orcid":false,"given":"Francesca","family":"Cardona","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cUgo Schiff\u201d, University of Firenze, via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy"},{"name":"Associated with Consorzio Interuniversitario Nazionale di Ricerca in Metodologie e Processi Innovativi di Sintesi (CINMPIS), 70100 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"jcs221739","DOI":"10.1242\/jcs.221739","article-title":"Lysosomal storage disorders\u2014challenges, concepts and avenues for therapy: Beyond rare diseases","volume":"132","author":"Marques","year":"2019","journal-title":"J. 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