title: Design and synthesis of novel 1,25-dihydroxyvitamin D3 analogues having a spiro-oxetane fused at the C2 position in the A-ring.
abstract: Four structurally novel stereoisomeric analogues of 1,25-dihydroxyvitamin D3 (3a-d) bearing a spiro-oxetane fused at the C2 position of the A-ring have been designed and synthesised in a convergent manner. The requisite A-ring enyne precursors (13a,b) for the vitamin D analogues (3a,b) and (3c,d), respectively, were synthesised from pentaerythritol according to an eleven-step procedure. Preliminary biological evaluation of the analogues using the bovine thymus vitamin D receptor (VDR) suggested that the incorporation of the spiro-oxetane moiety instead of a gem-dimethyl group at the C2 position had a beneficial effect on the VDR affinity.
authors.affiliation: Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Shido, Sanuki, Kagawa 769-2193, Japan. tofu@kph.bunri-u.ac.jp
authors.forename: Toshie
authors.initials: T
authors.lastname: Fujishima
authors.forename: Takato
authors.initials: T
authors.lastname: Nozaki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suenaga
mesh_terms: D000818:Animals; D002417:Cattle; D015195:Drug Design; D004988:Ethers, Cyclic / Q000737:chemistry*; D011485:Protein Binding; D018167:Receptors, Calcitriol / Q000737:chemistry / Q000378:metabolism; D013141:Spiro Compounds / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
chemical_list: D004988:Ethers, Cyclic; D018167:Receptors, Calcitriol; D013141:Spiro Compounds; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; C005287:oxetane
keywords: Hormone; Nuclear receptor; Oxetane; Steroid; Vitamin