Substituents azido

Yields of 130 from 126 = PhCHz 63%, (CHglzCH 57%, HOCH2 39%, HOzdCHzlz 32% 

The azido group is inert to boronic esters but reacts readily with alkyldichlorobo-ranes [70]. Section 8.4.1 describes the conversion of boronic esters into (alkyldichloro)boranes and their reaction with azides. 

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The rabbit FruA discriminates the enantiomers of its natural substrate with a 20 1 preference for D-GA3P (12) over its L-antipode [202], Assistance from anionic binding was revealed by a study on a homologous series of carboxylated 2-hydroxyaldehydes which showed optimum enantioselectivity when the distance of the charged group equaled that of 12 (Scheme 15, Fig. 11) [299], The resolution of racemic substrates is not, however, generally useful since the kinetic enantioselectivity for nonionic aldehydes is rather low [202], 3-Azido substituents (69) can lead to an up to 9-fold preference of enantiomers in kinetically controlled experiments [300] while hydroxyl (70 preference for the... 

Both 3-bromo- and 3-azido- substituents in thiochroman-4-one occupy a pseudo-equatorial site with H-3ax appearing as a dd with. 7=8.5 and 3.1 Hz at 64.98 and at 64.54 (/= 12.5 and 4.4 Hz), respectively <2002EJ0285>. The geminal methyl groups in 3,3-dichloro-thiochroman-4-one 1,1-dioxide 167, X = C1, are equivalent and appear as a... 

Also, the rigidification of the galactose ring was not sufficient to block the elimination of the 2-azido substituent of 17 even using the low-temperature reagent (Fig. 5). Another failure occurred with the isoxazole sulfone 19. Here, the heterocycle did not survive base treatment. The isoxazole sulfide precursor was also unstable to base (Fig. 6). 

Most transformations of other azoles into tetrazoles involve azido substituents for example, 5-azido-l,2,3-triazoles 753 with a C02Me group at C(4) rearrange at 5070 C in organic solvents into the 5-diazoester substituted tetrazoles 754 (Scheme 325) <1998J(P2)785>. For a comprehensive review on the preparation of tetrazoles from transformations of other heterocycles see <1998JPR687>. 

In order to further delineate the role of AZAL in azide mutagenicity, a number of structure-activity studies have been undertaken and the results are summarized in Table 3.2. The close structural analogues 3-chloroalanine (9) and 3-cyanoalanine (10) were both found to be non-mutagenic [30], underlining the importance of the azido substituent for genotoxicity. Interestingly, 0-acetylserine sulfhydrylase is quite catholic in the substrates... 

As part of our studies with azido-substituted drugs, we investigated further the nature of the biotransformation of the azido substituent, and the effect upon metabolism of other functionalities on the aryl ring, using phenyl azide (la) and a series of simple 4-substituted aromatic azides... 

The introduction of an azido substituent on the C-2 position of cytosine arabinoside (ara-C) (149) or adenosine arabinoside (ara-A) (154) has been found to confer favourable properties to these antimetabolites. Ara-C, one of the most effective drugs for the treatment of human acute myeloblastic leukaemia [176], is subject to rapid metabolic deamination, by deoxycytid-ine deaminase, to the inactive uridine derivative ara-U (152) Scheme 3.5), and the drug has a half-life of approximately 12 minutes in man [177]. Efforts to circumvent this problem by modifying the 2 -arah/ o-position led... 

Following conversion to the triphosphate, the role of the azido substituent of AZT in the interaction of the drug with viral RT is also uncertain. Enzyme inhibition studies have demonstrated that HIV RT has a of 2.8 for the natural substrate thymidine-5 -triphosphate, whereas... 

However, equivalent potency of enzyme inhibition has been reported for the triphosphates of 3 -deoxythymidine and 3 -amino-3 -deoxythymidine despite the weak antiviral activity of the parent nucleosides (163) and (90) in vitro, both of which are poor substrates for phosphorylation [213, 214]. These observations suggest that the antiviral aetivity of 2, 3 -dideoxynucleo-sides may depend less on the relative inhibitory activities of the triphosphates against isolated RT, but rather reflects the affinity of the parent nucleosides for the cellular kinase enzymes effecting triphosphorylation. Nevertheless, other studies of RT inhibition by nucleoside triphosphates have demonstrated a defined SAR for modifications at the 3 -position [215], and it is likely that the azido substituent of AZT contributes both to the requisite substrate activity for the cellular phosphorylating enzymes, and the specificity of RT inhibition following conversion to the triphosphate. 

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