Taxol, precursor

Magnus and co-workers (158-162) used the power of the oxidopyrylium cycloaddition to prepare a taxol precursor 288, generating a synthon for the taxol... 

A similar approach was employed en route to a synthesis of taxol precursors, as shown in Scheme 14 <1996T14081>. In this case, a [5+2] cycloaddition reaction of 133 yielded diastereoisomers 134a and 134b. 

Murugkar, A. Padhye, S. Guha-Roy, S. Wagh, U. Metal complexes of Taxol precursor 1. Synthesis, characterization and antitumor activity of the copper complex of 10-deacetylbaccatin thiosemicarbazone. Inorg. Chem. Commun., 1999, 2 545-548. 

A practical application of these studies is that an engineered strain of E. coli has been developed that yields taxadiene (A16.2) in a reasonable yield of 1-3 mg per liter of cell culture (565). This successful bioproduction of a taxol precursor suggests that future work in this area will lead to improved bioproduction of taxol or baccatin III. 

Ajikumar PK, Xiao WH, Tyo KE, Wang Y, Simeon F, Leonard E, Mucha O, Phon TH, Pfeifer B, Stepha-nopoulos G (2010) Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli. Science 330 70-74... 

Scheme 5.29 Cascade process in E. coli toward taxol precursors. Pathway engineering yields taxa-4(5),l 1 (12)-diene with subsequent C5 hydroxylation to taxadien-5a-ol catalyzed by an artificial fusion protein consisting of taxadiene-5a-hydroxylase and Taxus...

Ajikumar PK et al (2010) Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli. Science 330 70-74... 

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