Branched chain nucleosides synthesis

The synthesis of 7-(2,3,6-trideoxy-/ -L-gh/cero-hex-2-enopyranosyl-4-ulose)theophylline (71), which constitutes an important intermediate in the synthesis of branched-chain nucleosides (see Section VI), has been achieved42 by reaction54 55 of the 2, 3 -anhydroketonucleoside 59 with sodium iodide and sodium acetate. 

Synthesis of a Branched-chain Nucleoside from a Branched-chain... 

E xides and oxetanes react readily with lithiodithiane to give derivatives of 3- or y-hydroxy aldehydes or ketones. The method has been used for the multistep synthesis of an inomycin fragment, thietane prostaglandin analogs, branched-chain nucleoside sugars, the southern hexahydrobenzctfu-ran unit avermectin, the anti-Gram-positive bacterial elaiphylin andsyn-l,3-polyols. ... 

In a similar way it has been shown that reaction of mesylate 22, under aqueous basic conditions, affords the oxetane acid 23. This latter compound was used for a formal synthesis of the anti-viral oxetanocin. (See also Vol. 24, p. 217 and p. 176 for similar work.) The synthesis of other branched-chain nucleosides is covered in Chapter 20. 

A synthesis of the branched chain nucleoside analogue precursor 32 has been prepared by sequential treatment of dimethyl (2S)(3S)-2-aIlyl-3-hydroxygIutarate (prepared by yeast reduction of dimethyl 2-allyl-3-oxogIutarate) with ozone, acid resin and methanol then LAH. Branched-chain nucleosides are covered in Ch ter 20 and the preparation of C-linked glycosides and nucleosides are mentioned in Chapters 3 and 20 respectively. 

M. Nomura, S. Shuto, M. Tanaka, T. Sasaki, S. Mori, S. Shigeta, and A. Matsuda, Nucleosides and Nucleotides. 185. Synthesis and biological activities of 4 -a-C-branched-chain sugar pyrimidine nucleosides, J. Med. Chem., 42 (1999) 2901-2908. 

K. Augustyns, J. Rozenski, A. van Aerschot, R. Busson, P. Claes, and P. Hcrdewijn, Synthesis of a new branched-chain hexopyranosyl nucleoside—l-[2, 3 -dideoxy-3 -C-(hydroxymethyl)-ot-D-etyfhro-pentopyranosyl]- thymine, Tetrahedron 50 1189 (1994). 

Synthesis of 6-Chloro-9-(6 -deoxy-3 -C-methyl-2, 3, 4 -tri-0-methyl-/3-D-allopyrano-syl)purine A Branched-chain Sugar Nucleoside, G. B. Howarth, W. A. Szarek, and J. 

Rosenthal, A, Sprinzl, M, Branched-chain sugar nucleosides. IV. 9-(3-deoxy-3-C- hydroxymethyl -P(and a)-D-allofuranosyl and ribofuranosyljadenine. Can. J. Chem., Al, 4477-4481, 1969. Rosenthal, A, Catsoulacos, P, Synthesis of branched-chain sugars by the Wittig reaction. Can. J. Chem., 46, 2868-2872, 1968. 

The preparation of the branched-chain sugar found in the naturally occurring nucleoside antibiotic amipurimycin is depicted in Scheme 1. The synthesis involved deoxygenation at C-4 of a 3-ulose derivative with triphenyphosphine-iodine-imidazole in the first step. ... 

A new radical allylation procedure has been applied to the synthesis of a 3 -C-allyl-2, 3 -dideoxypyrimidine nucleoside, and lactone 121, made by photochemical addition of isopropanol to the corresponding 2,3-ene, has been converted to the nucleoside 122. Branched-chain sulfonates 123 have been made from 3 -ketonucleosides, and the isobutyl group was found to be superior to other possibilities, it being cleavable by iodide ion to give the sulfonic acid, an analogue of a 3 -phosphate. An ingenious route to related phosphonates is outlined in... 

An intermediate prepared from isopropylidene-D-glyceraldehyde via a Claisen rearrangement and previously used for the synthesis of some branched-chain fluorinated nucleosides (Vol. 32, p. 272-273), has now been used to make a fluorinated cyclopentane unit, to which was linked 6-chloropurine, thus leading to carbocyclic 2, 3 -dideoxy-4 -fluoro-L-adenosine (161). The same synthetic sequence could be modified to generate, via a metathesis step, an enantiomeric cyclopentane unit, and hence the enantiomer of 161, and equivalent structures with the other nucleobases. ... 

The branched-chain sugar nucleosides (54) and (55) have been prepared by conventional methods from the corresponding sugars, whose synthesis is referred to in Chapter 13. The branched-chain uridine derivatives show in vitro activity against cultured L1210 cells. ... 

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