Spiro nucleosides

The synthesis of the 4 -spiroannulated ribonucleoside was aceomplished by elimination of the 2 -phenylthio group of compound 132 via a controlled oxidation with Davis oxaziridine reagent. 

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Gimisis T, Chatgilialoglu C (1996) 1,5-Radical translocation protocol for the generation of C-1 radicals in nucleosides. Synthesis of spiro nucleosides through a rare 5-e do-trig cyclization. J Org Chem 61 1908-1908... 

In nature, there are many kinds of polycyclic ether antibiotics, so this method can be used for the construction of polycyclic ethers. Eq. 6.8 shows the preparation of spiro sugar ketals (15) at anomeric position [21-23]. Biologically attractive spiro-nucleosides at the anomeric position may be prepared by this procedure. 

Aza-TSAO is a bioisosteric derivative of the spiro nucleoside TSAO (Fig. 9), which is a potent HlV-1 inhibitor. The bioisosteric replacement leads to less active compounds [49]. The binding mode of several aza-TSAO derivatives of type 150 which show HIV RT inhibitory activity, was in-... 

Abstraction at acetal centers. Simpkins used a hydrogen atom abstraction from tetrahydrofuranyl and tetrahydropyranyl acetals for the preparation of spiroketals (Scheme 41, Eq. 41.1)] [137]. Malacria has inserted this process in a cascade reaction leading to functionalized cyclopentanone (Eq. 41.2) [138], Bertrand and Crich applied this reaction for the preparation of optically active cyclopentane derivative under chiral auxiliary control (Eq. 41.3) [139]. The synthesis of anomeric spiro-nucleosides was reported independently by Chatgilialoglu [46] and Kittaka [140]. In the example reported in Eq. (41.4), the gem-dibromovinyl derivative was treated with hexabutyldistannane to afford the desired spiro derivatives. This kind of reac-... 

Synthesis of spiro sugars and C-nucleosides using anomeric free radicals 98SL700. 

Balzarini J, Perez-Perez M-J, San-Felix A, Schols D, Perno C-F, Vandamme A-M, Camarasa M-J, De Clercq E. 2, 5 -Bis-0-(tert-Butyldimethylsilyl)-3 -spiro- 5" -(4" -amino-1", 2" -oxathiole-2", 2" -dioxide)pyrimidine (TSAO) nucleoside analogues highly selective inhibitors of human immunodeficiency virus type 1 that are targeted at the viral reverse transcriptase. Proc Natl Acad Sci USA 1992 89 4392-4396. 

Balzarini J, Velazquez S, San-Felix A, Karlsson A, Perez-Perez M-J, Camarasa M-J, De Clercq E. Human immunodeficiency virus type 1-specific [2, 5 -bis-0-(tert-butyldimethylsilyl)-(i-D-ribofuranosyl]-3 -spiro-5"-(4"-ami-no-1",2"- oxathiole-2",2"-dioxide)-purine analogues show a resistance spectrum that is different from that of the human immunodeficiency virus type 1 -specific non-nucleoside analogues. Mol Pharmacol 1993 43 109-114. 

A number of novel spiro heterocycles, including the triazepinethione 146 have been derived from 3-hydroxy-3-(2-oxocyclohexyl)indolin-2-one 145 by condensation with active methylene compounds <00SC1257>. A condensation process was also used to prepare tricyclic triazepinones related to the non-nucleoside reverse transcriptase inhibitor nevirapine <00JHC1539>. 

Hydantocidiu. Hydantocidin, C7H10N2O6, is elaborated by S. hygroscopicus. It is unique in that the anomeric carbon of the ribosyl moiety forms the spiro bond of hy dan torn. The nbofuranose moiety which has been reported to be in a Co-endo conformation has been synthesized. Hydantocidin is a herbieidal nucleoside with activity against monocotyledenous and dicotvledenous plants. 

With this normal mode description, then, it is instructive to review the resonance Raman intensity-derived excited-state structural dynamics. The first UV resonance Raman study of thymine was not done until 1994 by Lagant, et al. [113], Although Raman and IR spectra of thymine had been recorded much earlier. Most earlier studies of nucleic acid components focussed on the nucleosides and nucleotides. Indeed, much of the earlier research on nucleic acid components was done by the groups of Peticolas and Spiro, working independently. Spiro focussed more on nucleosides and larger nucleic acid structures (see below), while Peticolas examined the nucleobases initially. Peticolas s approach was to combine ab initio computations of the ground-state and excited-state structures and vibrational frequencies, with... 

In contrast to the isolated nucleobases, a significant amount of work has been done on the excited-state structural dynamics and UV resonance Raman spectroscopy of the nucleotides. The excited-state structural dynamics of nucleosides have not been determined to date, although some UV resonance Raman spectra of the nucleosides have been measured [139, 145, 146], This work on the nucleosides has been primarily for the application of UV resonance Raman spectroscopy in the determination of ground-state structure, rather than excited-state structural dynamics. This emphasis on the nucleotides is no doubt driven by their greater solubility, as well as their immediate relevance to the nucleic acids. In addition, it was believed that the vast majority of the intensity observed in the UV Raman spectra arose through resonance enhancement of the nucleobase chromophore. Much of the early work on the UV resonance Raman spectra of nucleotides and nucleosides was completed by the groups of Tsuboi, Spiro and Peticolas. 

This initial report was followed closely by the UV resonance Raman spectra of uridine (UMP), cytidine (CMP) and guanidine (GMP) monophosphates by Nishimura, et al. [149] and the application of UV resonance Raman spectroscopy to nucleic acids and their components started in earnest. In the years that followed, Peticolas and Spiro provided much of the research effort in this area. For nucleosides and nucleotides, Peticolas studied guanosine [150], UMP [151-154], GMP [152, 155], AMP [144, 152, 156] and CMP [153], Spiro was the only one to measure the UV resonance Raman spectra of TMP, in addition to those of all the other naturally occurring nucleotides [157, 158], For all of these nucleotides, UV resonance Raman excitation profiles have been determined. 

Stec extended his work on P-chiral phosphorothioates and described the synthesis of P-chiral, isotopomeric deoxyribonucleoside-phosphorothioates and -phosphates (76a-p) labelled with an oxygen isotope. To obtain stereodefined PS 0-oligos, the 5 -0-DMT-nucleoside-3 -0-(2-thio- spiro -4,4-pentamethy-lene-l,3,2-[0 ]oxathiaphospholanes were synthesised by phosphitylation of the correct protected nucleoside with chirally pure [O ]oxathiaphospholane, with subsequent sulfurisation. The resulting oxadithiaphospholanes were separated by chromatography into diastereomerically pure forms and individually treated with Se02 to yield the oxathiaphospholanes. ... 

Oxazine ring opening of the sugar spiro derivative 699 with phenylhydra-zine gave the 1,2,4-triazole C-nucleoside 702 through the intermediates shown in Scheme 187 (85CPB102),... 

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