Halogenations enzymatic

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. 

Several cyditol derivatives of varying ring size, for example, (69)/(70), have been prepared based on an enzymatic aldolization as the initial step. Substrates carrying suitably installed C,H-acidic functional groups such as nitro, ester, phosphonate (or halogen) functionalities made use of facile intramolecular nucleophilic (or radical) cyclization reactions ensuing, or subsequent to, the enzyme-catalyzed aldol addition (Figure 10.27) [134—137]. 

Vamvakas S, Dekant W, Berthold K, et al. 1987. Enzymatic transformation of mercapturic acids derived from halogenated alkenes to reactive and mutagenic intermediates. Biochem Pharmacol 36 2741-3748. 

Activated esters of halogenated alcohols, such as 2-chloroethanol, 2,2,2-trifluoroethanol, and 2,2,2-trichloroethanol, have been often used as substrate for enzymatic synthesis of esters, owing to an increase in the electrophilicity (reactivity) of the acyl carbonyl and avoid significant alcoholysis of the products by decreasing the nucleophilicity of the leaving alcohols. ... 

Thus, neither halogen substitution nor ring strain induces enzymatic hydrolysis. Molecules 21 and 22 may be bound in such a way that the (3-lactam carbonyl lies too far away from the catalytic serine hydroxyl group.72... 

Figure 7.25 Enzymatic reduction of a-halogenated propargylic ketones by LBADH...

Table 7 includes many structurally unique nonprotein amino acids with heterocyclic units as part of the structure. These amino acids are isolated from various sources and exhibit interesting bioactivities. In most cases, enzymatic modification of proline occurs through installation of hydroxyl groups, halogenated side chains, and alkyl side chains to give rise to the observed structural diversity. 

The production of 7-ADCA, which also traditionally was carried out chemically, in 1989 has been replaced by Gist-brocades (now DSM) by an enzymatic process so as to avoid the use of halogenated solvents. 

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

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