Synthesis of novel C -4ʹ-spiro-oxetano- α -L- ribo nucleosides

Novozym 435: the “perfect” lipase immobilized biocatalyst?

“…340 N435 has been used to produce 2′,3′,5′-tri-O-ace-tyl-4′-C-p-toluenesulfonyloxymethyl-β-D-xylofuranosylthymine and 2′,3′,5′-tri-O-acetyl-4′-C-p-toluenesulfonyloxymethyl-β-Dxylofuranosyluracil was used to produce C-4′-spiro-oxetano-α-Lribonucleosides. 341 Three citrus fruit-derived flavonoids (grapefruit extract, naringin, and neohesperidin dihydrochalcone) have been esterified with different fatty acids (e.g., omega-3 polyunsaturated fatty acids obtained from fish oil) in a reaction catalyzed by N435. 342 The conversions were over 85%, and the modification was in the primary alcohol of the glucose moiety of the flavonoids.…”

Advances in the Synthesis of Spirocyclic Nucleosides

“…The Prasad group synthesized novel C-4′-spirocyclic-oxetano--L-ribonucleosides in 39% and 45% overall yields using xylo-configured furanosyl thymine and uracil derivatives 395a and 395b synthesized using a chemoenzymatic approach involving the lipase Novozyme ® -435 (Scheme 59). 77 The Prasad group reported an enzyme-mediated synthesis of C-4′-spirocyclic-oxetano-xylofuranosyl nucleosides T and U (Scheme 60). 78 The precursor diol 405a,b was obtained from 402 in three steps consisting of acetolysis to 403a,b, Vorbrüggen nucleobase coupling with T and U to 404a,b, and treatment with methanolic ammonia resulted in deacetylation to afford 405a,b.…”

“…The Prasad group synthesized novel C -4′-spirocyclic-oxetano-α- l -ribonucleosides in 39% and 45% overall yields using xylo -configured furanosyl thymine and uracil derivatives 395a and 395b synthesized using a chemoenzymatic approach involving the lipase Novozyme ® -435 (Scheme 59 ). 77 . The nucleosides 395a , b were deacetylated with saturated methanolic ammonia and further underwent C -3′- and C -5′-hydroxy acetonide protection to give 397a , b , followed by mesylation of the free hydroxy group to form nucleosides 398a , b .…”

Chemoenzymatic Synthesis of arabino-Configured Bicyclic Nucleosides

“…In the past few years, our research group has aimed and successfully executed the synthesis of various sugar modified nucleosides following chemical and biochemical pathways. 6′-Methyl-2′-O,4′-C-methylene--L-ribofuranosylpyrimidines, 36 -L-ribofuranosylnucleosides, 37 C-4′spiro-oxetano--L-ribonucleosides 38 were synthesized following chemical pathway, whereas 2′-O,4′-C-methyleneribonucleosides C, 39 C-4′-spiro-oxetanoribonucleosides, 40 homolyxofuranosylpyrimidines D 41 were synthesized following chemoenzymatic pathway. Herein, a facile and efficient methodology has been described for the synthesis of LNA nucleosides 8a,b following a chemoenzymatic pathway (Figure 1).…”