Premium
An Efficient Method for the Preparation of 1′ α ‐Branched‐Chain Sugar Pyrimidine Ribonucleosides from Uridine: The First Conversion of a Natural Nucleoside into 1′‐Substituted Ribonucleosides
Author(s) -
Kodama Tetsuya,
Shuto Satoshi,
Nomura Makoto,
Matsuda Akira
Publication year - 2001
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20010601)7:11<2332::aid-chem23320>3.0.co;2-w
Subject(s) - chemistry , cytidine , anomer , pyrimidine , nucleoside , tautomer , uridine , yield (engineering) , natural product , stereochemistry , medicinal chemistry , organic chemistry , enzyme , rna , biochemistry , materials science , metallurgy , gene
The 1′ α ‐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′ α ‐branched‐chain sugar pyrimidine nucleosides. Successive treatment of 8 with LiHMDS and PhSeCl in THF at <−70 °C gave the desired 1′‐phenylseleno products in 85 % yield as an anomeric mixture of the 1′ α ‐product 11 and the 1′ β ‐product 12 ( 11 / 12 =2.5:1). Highly stereoselective reduction at the 2′‐carbonyl of the 1′ α ‐product 11 occurred from the β ‐face by using NaBH 4 /CeCl 3 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′ α ‐vinyluridine. With this procedure, 1′ α ‐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.