Novel Approach to Diastereoselective Synthesis of 2 -Deoxy[5 - 2 H 1 ]Ribonucleoside Derivatives by Reduction of the Corresponding 5 -O -Acetyl-2 -Deoxy-5 -Phenylselenoribonucleoside Derivatives With a Bu 3 Sn 2 H-Et 3 B System ETSUKO KAWASHIMA, 1 KEIZO TOYAMA, 1 KENSHIRO OHSHIMA, 1 MASATSUNE KAINOSHO, 2 YOSHIMASA KYOGOKU, 3 AND YOSHIHARU ISHIDO 1 * 1 Laboratory of Pharmaceutical Chemistry, Faculty of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo, Japan 2 Department of Chemistry, Faculty of Science, Tokyo Metropolitan University, Hachioji, Tokyo, Japan 3 Institute for Protein Research, Osaka University, Suita-shi, Osaka, Japan ABSTRACT Diastereoselective syntheses of [5'- 2 H]thymidine ( 6-T) [(5'R)/ (5'S)= 31:69] , N 4 -benzoyl-2'-deoxy[5'- 2 H]cytidine ( 6-C Bz ) [(5'R)/ (5'S) = 27:76], N 6 -benzoyl-2'- deoxy[5'- 2 H]adenosine ( 6-A Bz ) [(5'R)/ (5'S) = 39:61], and 2'-deoxy- N 2 -isobutyryl[5'- 2 H]guanosine ( 6-G iBu ) [(5'R)/ (5'S) = 20:80] were attained by a radical reductive deu- teration reaction of the corresponding 5' -O -acetyl-3' -O -TBDMS-2' -deoxy-5' - phenylselenoribonucleosides ( 4 ) with a Bu 3 Sn 2 H-Et 3 B system at <-70° C to give 5 ( 87– 98%yields), followed by unmasking (66–79%yields); 4 were synthesized in three steps of reactions from the corresponding 2'-deoxy-3'- O-TBDMS-5'- O-Ms-ribonucleosides ( 1 ) (88–93%yields) by a known method. Chirality 9:435–442, 1997. © 1997 Wiley-Liss, Inc. KEY WORDS: diastereoselective deuteration; (5'R)/ (5'S) -2'-deoxy[5'- 2 H]ribonucleo- sides; Bu 3 Sn 2 H-Et 3 B The strong demand from structural biologists for nucleo- sides labeled with stable isotopes with high diastereoselec- tivity and/ or site-specificity has currently given a great im- petus to synthetic organic chemists to develop a novel methodology for the synthesis of such appropriate inter- mediates, which are essential to construct an oligonucleo- tide bearing a desired nucleotide sequence. In view of this background, we have developed efficient methods for the synthesis of (2'R)- 1 and (2'S) -2'-deoxy[2'- 2 H]ribonucleo- sides, 2 ribonucleosides, and 2'-deoxyribonucleosides bear- ing 15 N labels on the exocylic amino groups of their het- erocylic moieties. 3 Moreover, we have also reported the synthesis of thymidine bearing a 2'-deoxy[1',2',3',4',5'- 13 C 5 ] D-ribofuranosyl moiety, which was incorporated into a DNA dodecamer for a heteronuclear 2D NMR study. 4 Incidentally, synthetic studies of diastereoisomers of [5'- 2 H]nucleosides with (5'R)- and (5'S)-configurations have been unambiguously achieved by glycosylation of a nucleic acid base with a D-ribose derivative that was chirally la- beled by a deuterio group in advance. The syntheses were not necessarily efficient, as the nucleosides were prepared from D-ribose in low overall yields over ten or more steps, and were confined to the adenosine 5 and 2'-deoxycytidine derivatives. 6 In a previous communication, 7 we described that the reduction of 5'- O-acetyl (Ac)-2'-deoxy-5'-phenylseleno (PhSe)-ribonucleosides ( 4 ) with Bu 3 Sn 2 H-Et 3 B was in- duced efficiently, with diastereoselectivity at the 5'- position. Moreover, we have shown the utility of the result- ing mixtures of (5'R)- and (5'S) -2'-deoxy[5'- 2 H 1 ]ribonu- cleosides, after constructing an oligonucleotide with the corresponding nucleotides, in an NMR spectroscopic analysis of the conformation sugar-phosphodiester back- bone structure. 8 The elucidation of the variety of delicate conformational changes induced by the formation of a com- plex of a nucleic acid with a protein is an important aspect, particularly in connection with protein or ligand induced distortions of DNA structure, 9 in the field of structural bi- ology. We now report in detail the results involving the radical reduction of 4 with a Bu 3 Sn 2 H-Et 3 B system. RESULTS AND DISCUSSION We have searched for appropriate materials for the syn- theses of the title compounds in terms of a chemical con- version of commercially available nucleosides, and have confirmed the utility of 5'- O-Ac -2'-deoxy-5'-PhSe-ribo- nucleosides ( 4 ), one of which has been reported by Hara- guchi and coworkers 10 to be the intermediate for the syn- thesis of a 5'- C-allyluridine derivative via 2,2'-anhydro- - D- *Correspondence to: Yoshiharu Ishido, Lab. of Pharmaceutical Chemistry, Faculty of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-03, Japan. Received for publication 22 November 1996; Accepted 14 May 1997 CHIRALITY 9:435–442 ( 1997) © 1997 Wiley-Liss, Inc.