TY - JOUR
T1 - 1,2,4-Diazaphosphole nucleosides. Synthesis, structure, and antitumor activity of nucleosides with a ;3phosphorus atom
AU - Riley, Timothy A.
AU - Larson, Steven B.
AU - Avery, Thomas L.
AU - Finch, Rick A.
AU - Robins, Roland K.
PY - 1990/2
Y1 - 1990/2
N2 - Glycosylation of 1, 2, 4 λ3-diazaphosphole (4) under Lewis acid catalyzed conditions gave 1-α-D-ribofuranosyl-1, 2, 4 λ3diazaphosphole (5) as the only product. Ethyl 1, 2, 4 λ3diazaphosphole-3-carboxylate (10) was synthesized by the cyclocondensation of ethyl (chlorophosphinidene)(trimethylsilyl)acetate (8) with (trimethylsilyl)diazomethane and subsequent desilylation with tetra-n-butylammonium fluoride. Reaction of 10 with methanolic ammonia at 80 °C gave 1,2, 4 λ3-diazaphosphole-3-carboxamide. Glycosylation of 10 using trimethylsilyl triflate catalyst followed by ammonolysis gave the ribavirin (1) analogue 1-β-D-ribofuranosyl-1, 2, 4 λ3-diazaphosphole-3-carboxamide (11). Acetylation of 11 and subsequent treatment with phosphorus pentasulfide gave 2',3',5'-tri-O-acetyl-l-β-D-ribofuranosyl-1, 2, 4 λ3-diazaphosphole-3-thiocarboxamide (13). Deprotection with methanolic ammonia gave 1-β-D-ribofuranosyl-1, 2, 4 λ3-diazaphosphole-3-thiocarboxamide (14). Compound 14 gave a 25% increase in life span (ILS) against L1210 in female BDF1mice. The anomeric configuration and site of glycosylation of 5 and 13 were established by single-crystal X-ray crystallography.
AB - Glycosylation of 1, 2, 4 λ3-diazaphosphole (4) under Lewis acid catalyzed conditions gave 1-α-D-ribofuranosyl-1, 2, 4 λ3diazaphosphole (5) as the only product. Ethyl 1, 2, 4 λ3diazaphosphole-3-carboxylate (10) was synthesized by the cyclocondensation of ethyl (chlorophosphinidene)(trimethylsilyl)acetate (8) with (trimethylsilyl)diazomethane and subsequent desilylation with tetra-n-butylammonium fluoride. Reaction of 10 with methanolic ammonia at 80 °C gave 1,2, 4 λ3-diazaphosphole-3-carboxamide. Glycosylation of 10 using trimethylsilyl triflate catalyst followed by ammonolysis gave the ribavirin (1) analogue 1-β-D-ribofuranosyl-1, 2, 4 λ3-diazaphosphole-3-carboxamide (11). Acetylation of 11 and subsequent treatment with phosphorus pentasulfide gave 2',3',5'-tri-O-acetyl-l-β-D-ribofuranosyl-1, 2, 4 λ3-diazaphosphole-3-thiocarboxamide (13). Deprotection with methanolic ammonia gave 1-β-D-ribofuranosyl-1, 2, 4 λ3-diazaphosphole-3-thiocarboxamide (14). Compound 14 gave a 25% increase in life span (ILS) against L1210 in female BDF1mice. The anomeric configuration and site of glycosylation of 5 and 13 were established by single-crystal X-ray crystallography.
UR - http://www.scopus.com/inward/record.url?scp=0025069980&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025069980&partnerID=8YFLogxK
U2 - 10.1021/jm00164a016
DO - 10.1021/jm00164a016
M3 - Article
C2 - 1967649
AN - SCOPUS:0025069980
SN - 0022-2623
VL - 33
SP - 572
EP - 576
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 2
ER -