An efficient method for the preparation of 1'alpha-branched-chain sugar pyrimidine ribonucleosides from uridine: the first conversion of a natural nucleoside into 1'-substituted ribonucleosides.
The 1'alpha-phenylselenouridine derivative 13 was successfully synthesized by enolization of the 3',5'-O-TIPDS-2'-ketouridine 8, and was subjected to a radical reaction with a vinylsilyl tether--an efficient procedure for preparing 1'alpha-branched-chain sugar pyrimidine nucleosides. Successive treatment of 8 with LiHMDS and PhSeCl in THF at < -70 degrees C gave the desired 1'-phenylseleno products in 85% yield as an anomeric mixture of the 1'alpha-product 11 and the 1'beta-product 12 (11/12= 2.5:1). Highly stereoselective reduction at the 2'-carbonyl of the 1'alpha-product 11 occurred from the beta-face by using NaBH4/CeCl3 in MeOH, and subsequent introduction of a dimethylvinylsilyl tether at the 2'-hydroxyl gave the radical reaction substrate 14. The photochemical radical atom-transfer reaction of 14 by using a high-pressure mercury lamp proceeded effectively in benzene to give the exo-cyclized PhSe-transferred product 18, in which (PhSe)2 proved to be essential as an additive for radical atom-transfer cyclization reactions. Subsequent phenylseleno-group elimination of 18 gave the sugar-protected 1'alpha-vinyluridine. With this procedure, 1'alpha-vinyluridine (22) and -cytidine (25), designed to be potential antitumor agents, were successfully synthesized. This study is the first example of functionalization at the anomeric 1'-position of a nucleoside by starting from a natural nucleoside to produce a ribo-type 1'-modified nucleoside.
Kodama
T
T
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Shuto
S
S
Nomura
M
M
Matsuda
A
A
D003500:Cyclization; D003561:Cytarabine / Q000031:analogs & derivatives / Q000737:chemistry; D003562:Cytidine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000737:chemistry; D006031:Glycosylation; D015394:Molecular Structure; D016566:Organoselenium Compounds / Q000138:chemical synthesis*; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D012643:Selenium / Q000737:chemistry*; D012825:Silicon / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014529:Uridine / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D014753:Vinyl Compounds / Q000138:chemical synthesis
C430924:1'-phenylselenouridine; C430814:1'-vinylcytidine; C430813:1'-vinyluridine; C103084:1-(3-C-ethynylribopentofuranosyl)cytosine; D016566:Organoselenium Compounds; D011741:Pyrimidine Nucleosides; D012263:Ribonucleosides; D014753:Vinyl Compounds; D003561:Cytarabine; D003841:Deoxycytidine; C070279:2'-cyano-2'-deoxyarabinofuranosylcytosine; D003562:Cytidine; C056034:2'-deoxy-2'-methylenecytidine; D012643:Selenium; D014529:Uridine; D012825:Silicon