Synthesis and testing of 2alpha-modified 1alpha,25-dihydroxyvitamin D(3) analogues with a double side chain: marked cell differentiation activity.
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.
Suhara
Yoshitomo
Y
Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa, Japan.
Kittaka
Atsushi
A
Kishimoto
Seishi
S
Calverley
Martin J
MJ
Fujishima
Toshie
T
Saito
Nozomi
N
Sugiura
Takayuki
T
Waku
Keizo
K
Takayama
Hiroaki
H
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
D000480:Alkynes; D000970:Antineoplastic Agents; D008024:Ligands; D018167:Receptors, Calcitriol; D002117:Calcitriol