6-Halogeno-6-deoxy derivative

Dianhydrides react with other nucleophilic or electrophilic reagents in a steric course similar to that operating with water under basic or acid catalysis, to give amino, halogeno, and thio derivatives (see Sects. VI and VII). Catalytic reduction in the presence of Raney nickel,540,746 or with lithium aluminum hydride,155 331 affords the mono-155 331 746 and di-746 deoxy derivatives of 1,6-anhydrohexoses (see Sect. VII,3,a,ii). 

Modification of the primary, 6"-hydroxyl group of kanamycin A has been extensively studied by Umezawa and coworkers. Tetra-N-(benzyl-oxycarbonyl)kanamycin A was selectively p-toluenesulfonylated or naphthalenesulfonylated at 0-6" and the product converted into the corresponding chloro (216) and iodo derivative. - Catal) c hydrogenation of the iodo derivative gave " 6"-deoxykanamycin A (217). These 6"-halogeno and 6"-deoxy derivatives have an activity similar to that of the parent antibiotic. Kanamycin-6"-uronic add (218), its esters, and amide, and kanamycin 6"-phosphate (Ref. 245) (219) and 4",6"-0-benzylidene-kanamycin were prepared and found to have decreased antibacterial activity. 

D-lyxopyranosyl nucleosides with hydrogen halides to give the 3 -bromo- or 3 -chloro-3 -deoxy-nucleosides (406), or a mixture of the 2 - and 3 -fluoro-deoxy-nucleosides (407). 9-(3-Deoxy-3-iodo-)3-D-xylofuranosyl)hypoxanthine has been synthesized and converted into 3 -amino-3 -deoxy- and 3, 4 -unsatu-rated nucleosides as shown in Scheme 138. Both l-(2-deoxy-2-fluoro- and 2-chloro-2-deoxy-j8-D-arabinofuranosyl)cytidine have been prepared from the corresponding halogeno-sugar derivatives by standard methods (see Schemes 43 and 46). ... 

Stereospecific dependencies of the nonselective relaxation-rates for other protons in a sugar molecule may be seen in the data for a set of 3,4,6-tri-O-acetyl-l-0-benzoyl-2-deoxy-2-bromo-D-hexopyranose derivatives (40-42), as well as other 2-halogeno derivatives. A comparison of their... 

Selective chlorination or bromination of the 5 -hydroxyl group in unprotected D-ribonucleosides has been achieved75 by treatment with thionyl chloride or thionyl bromide, respectively, in hexamethyl-phosphoric triamide at room temperature for 10-15 hours the 5 -deoxy-5 -halogeno derivatives of cytidine and adenosine have been prepared in this way. The reactions presumably occur by way of alkoxyphosphonium salts as intermediates.78... 

A wide variety of natural and synthetic variations is permissible at C5", and at C6" for C 5 branched compounds (41). An extensive study of C6" modificationsof kanamycin B revealed that halogeno, azido, amino, alkylthio, and alkoxy substitutions are all well tolerated until they become very bulky (70). For example, only the N-hexanoyl-N-butylarnino derivative was essentially inactive against all bacteria tested, but the smaller substituents retained good activity. The NMR structure of gentamicin Cla (which is 5 deoxy) indicates that any modification at C 5 would be directed away from 30S (60). The predicted lack of interaction between C5" substituents and 308 explains why a variety of small substitutions is permissible. 

Dideoxynucleosides can also be prepared by hydrogenolysis of 2, 3 -dideoxy-2 -thio [158], 2, 3 -dideoxy-3 -thio [159, 160], 8,3 -S-anhydronucleo-sides of purine [161] and 2, 3 -dideoxy-3 -halogenoderivatives of nucleosides [52,162,163]. The intermediate dideoxy-3 -thio and 3 -halogeno derivatives can be easily prepared by nucleophilic displacement of the sulfonyloxy group of 2 -deoxy-3 -0-mesyl or tosyl nucleosides with mercaptide anion or with halide ion, respectively. The procedure has been successfully used for the synthesis of 3 -deoxythymidine 109h, 2, 3 -dideoxyuridine 109i and 2, 3 -dideoxy-5-... 

Treatment of 5-deoxy-5-halogeno nucleosides of adenine and uracil with trimethylamine yielded the corresponding 5-deoxy-5-trimethylammonium salts, whose interaction with anionic polynucleotides was then examined. Various A -alkyl, A -cycloalkyl, and iV-alkaryl derivatives of 3-amino-3-deoxy-and 3, 5 -diamino-3, 5 -dideoxy-adenosine have been prepared from the amino-sugar nucleosides the 3 -benzylamino derivative gave the unusual oxazolidine derivative (52). ° ... 

The syntheses of D-3-modified (Cl, Br, OMe) myo-inositol 1,4,5 trisphosphates as probes for the D-1,4,5 IP3/d-1,3,4,5-IP4 functional interface have been described. In the case of the halogeno derivatives, the known (A.P. Kozikowski et. al.. Cancer Chemother. Pharmacol., 1991, 29, 95) D-3-deoxy-3-halogeno-m> o-inositols were the starting materials and methylation of the known (J.P. Vacca et. al., J. Am. Chem. Soc., 1987, 109, 3478) D-4-0-benzyl-3-0-camphanoyl-l,2 5,6-di-0-cyclohexylidene-mj inositol provided access to the 3-0-methyl derivative. 

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