Atazanavir synthesis

Figure 13.7 Enzymatic reduction for the production of a chiral intermediate used in atazanavir synthesis.

Scheme 32 Use of the Kumada-Corriu reaction in the synthesis of Atazanavir...

As the examples illustrate, the synthesis of biaryls has received much attention. One reason is because they are difficult to synthesize, another is that they are often candidates for new drugs. The product in the Suzuki coupling, for example, is an intermediate in the synthesis of atazanavir, a protease inhibitor used in the treatment of HIV-AIDS. Numerous other classes of compounds are accessible by appropriate choices of reactants. 

Atazanavir 78 is an acyclic aza-peptidomimetic and potent HIV protease inhibitor [176,177]. The synthesis of atazanavir required [S)-tertiary leucine 99 (Figure 11.29). The same building block is also a key chiral amino acid required for a number of other drugs containing peptides such as Atazanavir, Boceprevir and Telaprevir [178,179]. 

Atazanavir 21 is an acyclic aza-peptidomimetic and potent human immimodeficiency virus (HfV) protease inhibitor [44, 45]. (S)-Tertiary leucine 22 (Figure 4.8) is a key intermediate required for the synthesis of atazanavir along with other drugs containing peptides such as boceprevir and telaprevir [46,47]. 

Atazanavir enzymatic synthesis of (1S,2/ )-[3-chloro-2-hydroxy-1(phenylmethyl) propyl]-carbamic acid,1,1-dimethylethyl ester. 

Synthesis of Atazanavir (HIV Protease Inhibitor) The main flame of atazanavir (AT), an acyclic aza-peptidomimetic, potent HIV protease inhibitor was prepared using biocatalytic asymmetric reduction. As shown in Scheme 33.11, (15)-chloroketone ((5))-ATl) was reduced diastereoselectively by Rhodococcus erythropolis SC 13845 to provide (15,2/ )-aminoalcohol (AT2) in 98.2% de with 99.4% ee. ... 

SCHEME 33.11. Synthesis of main flame of atazanavir by reduction with Rhodococcus erythropolis SC 13845. 

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