2-(3'-Hydroxypropylidene)-1alpha-hydroxy-19-norvitamin D compounds with truncated side chains.
Our recent studies with 2-(3'-hydroxypropylidene) analogs of 1alpha,25-dihydroxy-19-norvitamin D(3) showed that this 2-substituent creates compounds with very potent biological activity. In the continuing search for vitamin D compounds with selective activity profiles, we prepared a series of 1alpha-hydroxy-19-norvitamin D analogs characterized by the presence of a 3'-hydroxypropylidene substituent at C-2 and a truncated side chain. These vitamin D compounds were efficiently prepared using convergent syntheses. The C,D-fragments, namely the Grundmann ketones 19, 20, 27, 36 and 37 were synthesized from the known 8beta-benzoyloxy-22-aldehydes 12 and 29. These hydrindanones were subjected to Lythgoe type Wittig-Horner coupling with phosphine oxide 21, prepared by us previously, and after hydroxyl deprotection the set of 19-norvitamins 7-11 was successfully obtained. According to our expectations, all analogs (with an exception of the 20R-compound 7) have pronounced in vitro activity. When compared to the natural hormone 1alpha,25-(OH)(2)D(3) (1), they show the same or only slightly reduced affinity for the vitamin D receptor while being similarly effective as 1 in differentiation of HL-60 cells into monocytes.
Glebocka
Agnieszka
A
Department of Chemistry, Warsaw University, Pasteura 1, 02-093 Warsaw, Poland.
Sicinski
Rafal R
RR
Plum
Lori A
LA
DeLuca
Hector F
HF
D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D015394:Molecular Structure; D051381:Rats; D018167:Receptors, Calcitriol / Q000378:metabolism
D018167:Receptors, Calcitriol; D002117:Calcitriol