title: 26-Desmethyl-2-methylene-22-ene-19-nor-1α,25-dihydroxyvitamin D3 compounds selectively active on intestine.
abstract: Six new analogs of 2-methylene-19-nor-1α,25-dihydroxyvitamin D3, 6-7 and 8a,b-9a,b, have been synthesized. All compounds are characterized by a trans double bond located in the side chain between C-22 and C-23. While compounds 6 and 7 possess C-26 and C-27 methyls, compounds 8a,b and 9a,b lack one of these groups. A Lythgoe-based synthesis, employing the Wittig-Horner reaction was used for these preparations. Two different types of Δ(22)E-25-hydroxy Grundmann's ketone, having either only one stereogenic center located at position C-20 (20 and 21), or two stereogenic centers located at 20- and 25-positions (24a,b-25a,b) were obtained by a multi-step procedure from commercial vitamin D2. The introduction of a double bond at C-22 appeared to lower biological activity in vitro and in vivo. Further removal of a 26-methyl in these analogs had little effect on receptor binding, HL-60 differentiation and CYP24A expression but markedly diminished or eliminated in vivo activity on bone calcium mobilization while retaining activity on intestinal calcium transport.
authors: Department of Biochemistry, College of Agriculture and Life Sciences, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, USA.
authors: Grazia
authors: G
authors: Chiellini
authors: Department of Biochemistry, College of Agriculture and Life Sciences, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, USA.
authors: Pawel
authors: P
authors: Grzywacz
authors: Department of Biochemistry, College of Agriculture and Life Sciences, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, USA.
authors: Lori A
authors: LA
authors: Plum
authors: Department of Biochemistry, College of Agriculture and Life Sciences, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, USA.
authors: Margaret
authors: M
authors: Clagett-Dame
authors: Department of Biochemistry, College of Agriculture and Life Sciences, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, USA. Electronic address: deluca@biochem.wisc.edu.
authors: Hector F
authors: HF
authors: DeLuca
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002118:Calcium / Q000097:blood / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000187:drug effects*; D009928:Organ Specificity / Q000187:drug effects; D051381:Rats; D018167:Receptors, Calcitriol / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D018167:Receptors, Calcitriol; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D002117:Calcitriol; D002118:Calcium
keywords: Calcemic activity; Transcription activity; Vitamin D