2,2 -Cyclonucleoside ring

Thietane ring from 3-(acylthio)alcohols with 2,2 -cyclonucleoside ring opening ... 

Cyclonucleoside ring opening with and without epimerization... 

Several examples of the synthesis of cyclonucleoside derivatives by radical ring-closure reactions are also available <1996T9496, 1999J(P1)1257, 2000T8689, 2002CBC534, 2005EJ04640>. 

Many examples of compounds in which a heterocyclic ring is fused to a purine have been recorded. These include the various types of cyclonucleosides such as (210). However in this chapter a discussion of these compounds is not practical and for further details the reader should consult works devoted to nucleoside chemistry. Appropriate references are collected in Table 2. 

The fused heterocyclic rings to be discussed here have normally been produced by an intramolecular cyclization of an N(6)-, N(2)- or S-substituent onto a ring nitrogen atom in the purine nucleus and are mainly five- or six-membered systems cyclonucleosides such as (210) are of course notable exceptions and a few miscellaneous examples exist. 

Protected /3-D-ribofuranose and 3(2//)-pyridazinones gave the N-glucosides, whereas 4-amino-3-chloro-6(l//)-pyridazinone afforded the O-glycoside (87MI27). In the formation of pyridazine cyclonucleosides, either the 2 - (75) or 5 -hydroxy group (76) was involved in ring formation (83JOC3765). 

The Mitsunobu reaction has been used previously to prepare 5 -0-acylnucle-osides and nucleoside 5 -phosphates [111, 112]. With purine nucleosides, the approach failed (< 1 % yields) in the preparation of 5 -phosphates, the main product being N3,5"-cyclonucleosides resulting from an intramolecular nucleophilic attack by a purine ring nitrogen atom on the 5 -carbon atom. The predominant formation of the purine cyclonucleosides was attributed to electrostatic interactions between the phosphorus cation and the purine base which brought the reaction sites (5 and 3-N) close enough to favor cyclization [113]. 

Several reports have appeared concerning phosphates of cyclonucleosides in which the base is cyclized to the sugar ring. Phosphomonoesters and dinucleoside monophosphates containing 8,2 -thioanhydro-adenosine (9),... 

Goodman has reviewed neighboring-group participation in Volume 22 of this Series,366 and this subject will therefore not be discussed comprehensively in the present article. However, Goodman specifically excluded from his review the formation of anhydro sugars by oxide ion displacements, and also the formation of anhydronucleosides ( cyclonucleosides ). These topics will therefore be discussed, together with ring contractions and alkoxyl participations, because most of the literature on these subjects has not been reviewed previously. 

The 3,3 -cycloadenosine derivative (605) and 5 -chloro-5 -deoxyadenosine 2, 3 -sulphate (606) were formed when adenosine reacted with sulphuryl chloride in acetonitrile. Solvolysis of (606) in aqueous ethanol resulted in opening of the pyrimidine ring and formation of the cyclonucleoside (607). 3,5 -Cycloadenosine was synthesized from 5 -chloro-5 -deoxyadenosine, which was prepared by treating adenosine with thionyl chloride in HMPT. 

Novel nucleoside analogues have been prepared by thermal intramolecular addition of the 5 -azido group of the uridine derivative (58) to the 5,6-doubIe bond of the pyrimidine ring. The main product was shown to be the macrocycle (59) together with some of the 6-amino-6,5 -cyclonucleoside. Heating... 

C 3 cannot be ruled out since treatment of 2 -deoj - 5 -0-monomethojQrtrityl-adenosine with DAST afforded N, 3 -cyclonucleoside in good yield. 3 -Fluoro-xylosyladenine 4a, however, should be prepared readily by opening the epoxide ring of 2, 3 -anhydroadenosine with fluoride. ... 

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