title: Synthesis and testing of 2alpha-modified 1alpha,25-dihydroxyvitamin D(3) analogues with a double side chain: marked cell differentiation activity.
abstract: The 2alpha-methyl-, 2alpha-(3-hydroxypropyl)-, and 2alpha-(3-hydroxypropoxy)-derivatives of the 'double side chain' analogue of 1alpha,25-dihydroxyvitamin D(3) were synthesized using Trost A-ring/CD-ring connective strategy. Regarding the requisite A-ring building blocks, a new, high yield and stereoselective route to the 2alpha-methyl compound starting from D-glucose was developed. All three new analogues showed potent HL-60 cancer cell differentiation activity.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa, Japan.
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Suhara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kittaka
authors.forename: Seishi
authors.initials: S
authors.lastname: Kishimoto
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Calverley
authors.forename: Toshie
authors.initials: T
authors.lastname: Fujishima
authors.forename: Nozomi
authors.initials: N
authors.lastname: Saito
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sugiura
authors.forename: Keizo
authors.initials: K
authors.lastname: Waku
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takayama
mesh_terms: D000480:Alkynes / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D008024:Ligands; D018167:Receptors, Calcitriol / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000480:Alkynes; D000970:Antineoplastic Agents; D008024:Ligands; D018167:Receptors, Calcitriol; D002117:Calcitriol