Carbocyclic oxetanocin

Chiral cyclobutanes can be prepared by cycloaddition of alkenes substituted with one or more chiral auxiliary groups. A diastereofacial selectivity of 95% was observed in the diethylalu-minum chloride catalyzed cycloaddition of 1,1-dimethoxyethene (36) with ( — )-dimenlhyl-3-yl fumarate (37).16 The chiral cyclobutane 38 has been used as an intermediate in the synthesis of carbocyclic oxetanocin analogs. 

A total enantioselective synthesis of antiviral carbocyclic oxetanocins 289 and 290 was also completed by the Ichikawa group by utilizing a... 

Asymmetric [2 + 2] cycloaddition reaction affords a practical means of synthesis of optically active cyclobutanes, which can be used as useful intermediates in organic synthesis [138]. Narasaka reported that asymmetric [2 -i- 2] cycloaddition between acryloyl oxazolidinone derivatives and bis(methylthio)ethylene proceeded with high enantios-electivity when catalyzed by TADDOL-derived titanium complex (Sch. 58) [139]. The cyclobutane product was transformed into carbocyclic oxetanocin analogs or (-n)-grand-isol [140]... 

Hayashi S, Norbec DW, Rosenbrook W, Fine RL, Matsukura M, Planner J, Broder S. Mitsuya H. Cyclobut-A and cyclobut-G, carbocyclic oxetanocin analogues that inhibit the replication of HIV in T-cells and monocytes and macrophages in vitro. Antimicrob Agents Chemocher 1990 34 287-294. 

The cyclobutyl nucleosides (149) have been prepared they are related structurally to carbocyclic oxetanocin analogues of known antiviral activity (Vol. 23, p. 197-8), but were inactive.2 3 Other references to oxetanocin analogues are given in Chapter 19. 

The previously described 7-deazapurine carbocyclic nucleoside synthesis (see Scheme 1) indicated that the most efficient route to 22 would be via reaction of the protected chiral amine 23 with the dimethylacetal of 2-(2-amino-4,6-dichloropyrimidin-S yl)acetaldehyde followed by ring closure, hydrolysis and dqirotection. A review of the literature revealed two enantioselective routes to cyclobutyl derivatives that had been used in the chiral synthesis of carbocyclic oxetanocins and could be employed for preparing a precursor to 23. In one case, however, the initial step involved a [2-i-2]-cycloaddition reaction of not easily obtainable reagents in the presence of a chiral titanium compound as... 

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