Enzymatic halogenation

Cyclases are also responsible for NRP depsipeptide and PK lactone cyclization. For example, a di-domain excised from fengydn synthase was able to catalyze the formation of a macrolactone through the formation of a C—O bond [25]. Several cyclases from PK synthases have also been characterized to be functional, including the epothilone D cyclase [26, 27] (Equation 8.1). 

---

Considering the tremendous progress made in recent years to understand and utilize enzymatic halogenations in stereoselective synthesis, this area will continue to receive significant attention and interesting new developments can be expected in the years to come. 

Yaipakdee P, Robertson LW (2001) Enzymatic Halogenation of Flavanones and Flavones. Phytochemistry 57 341... 

Morris DR, Hager LP (1966) Mechanism of the inhibition of enzymatic halogenation by antithyroid agents. J Biol Chem 241 3582-3589... 

Franssen MCR, van Boven HG, van der Plas HC (1987) Enzymatic halogenation of pyr-azoles and pyridine derivates. J Heteroatom Chem 24 1313-1316... 

Jumago, are easily obtained. Chloroperoxidase can also be obtained in larger quantities from the fungus Curvularia inaequalisi40K Thus, a number of different haloperoxidases from various sources are available in quantities necessary for the enzymatic halogenation of organic compounds. 

Enzymatic halogenation catalyzed by haloperoxidases and perhydrolases involves the oxidation of halide ions to a halonium ion species which leads to the formation of hypohalous acids (Fig. 16.9-1). The products obtained by enzymatic halogenation with these enzymes are the same as the products obtained by chemical electrophilic halogenation with hypohalous acids. The differences in the para ortho ratios in the halogenation of some aromatic compounds could be due to a mixture of halogenation at or near the active site and in solution. 

The major advantage of enzymatic halogenation using haloperoxidases and perhydrolases is that the enzymes have a very low substrate specificity and that no free halogen is needed which makes halogenation catalyzed by these enzymes less hazardous than chemical halogenation. 

Comparison of Chemical with Enzymatic Halogenation 1277 References 1278... 

No enzymatic halogenation occurred with substrates lacking the j3-dicarbonyl structural element. Also 15a-hydroxylatlon of 1-dehydrotestoloactone by Penicillium sp. Work by Brown and Hager [J. Am. Chem. Soc. M, 719 (1967)] indicates that the enzymatic reaction involves generation of Cl" from Cl" and hydrogen peroxide. The inference may be drawn that there is no steroid-enzyme interaction required in the halogenation examples shown by Neidleman. 

In view of the predominant chemical nature of biohalogenation, it seems that enzymatic halogenation reactions involving haloperoxidase enzymes do not show... 

SCHEME 43.1. Murai et al. s synthesis of C15 acetogenins via enzymatic halogenation. 

ENZYMATIC HALOGENATION IN STEREOSELECTIVE SYNTHESIS TABLE 45.1. Examples of Halometabolites and Their Applications... 

Blasiak LC, Drennan CL. Structural perspective on enzymatic halogenation. Acc. Chem. Res. 2009 42 147-155. 

---