Biological epoxidation reactions

A prominent example of such a reaction is the biological epoxidation of the poly ene squalene... 

The mechanisms and the regio- and stereo-selectivity of epoxide reactions have been reviewed.39 The review also covers the role of epoxides in biologically important reactions. The achiral and chiral catalysts used in these reactions are discussed. A second review40 discusses the ring-opening reactions of oxiranes with carbon nucleophiles. 

The stereoselective synthesis of (+)-polyoxin J is accomplished by Gosh in 24 steps and 3 % overall yield. The key intermediates are protected thymine polyoxin C 8 and the 5-Ocarbamoyl polyoxamic acid 2, which were synthesized from D-ribose and dimethyl L-tartrate. Key steps are two different epoxidation reactions, one carried out with MCPBA and the other under Sharpless conditions with the D-(-)-tartrate. Both epoxides are opened with diisopropoxytitanium diazide. The coupling of the two fragments was realized with the BOP reagent 37. This synthesis provides an easy access to the synthesis of various (+)-polyoxin J analogs for biological evaluation. 

In conclusion, a Sharpless asymmetric epoxidation reaction may be used to achieve regioselectivity in a complex molecule containing two allylic alcohol moieties with opposite topicity. Thus, 32 could be alternatively converted into laulimalide (1) and its C-20 regioisomer simply by switching the chiral additive from +)- R,R)- to -)- S,S)-diisopropyl tartrate (DIPT). Biological tests have shown that the natural compound 1 is by far the most active one compared to other derivatives such as the C-20 regioisomer. 

Biological enzymes are well known to carry out epoxidation. For example, MMO is an efficient and selective catalyst for epoxidation of small terminal olefins such as ethylene, propylene, and 1-butene [246,247]. Lipases have been used to generate peroxoacids which in turn are used for epoxidation reactions [248,249]. The subject has been reviewed [250]. Biocatalytic systems are of interest not only because they can carry out enantioselective epoxidation of substrates, but also because they offer the exciting possibility of being engineered for specific transformations of nonnatural reagents. 

EIGURE 22.20 Polyols of a given triglyceride prepared via (a) epoxidation reaction and (b) hydrofoimylation reaction. With permission from Petrovic ZS. Polymers from biological oils. Contemp Mater 2010 I-l 39-50. 

Alkylamines have a variety of applications in the chemical industry as starting materials for the preparation of insecticides and pharmaceuticals. Labetalol, for instance, a so-called /3-blocker used for the treatment of hi h blood pressure, is prepared by SN2 reaction of an epoxide with a primary amine. The substance marketed for drug use is a mixture of all four possible stereoisomers, but the biological activity derives primarily from the (R,R) isomer. 

Chapter 7, Alkenes Reactions and Synthesis—Alkene epoxidation has been moved to Section 7.8, and Section 7.11 on the biological addition of radicals to alkenes has been substantially expanded. 

Since the seminal contributions by Nugent and RajanBabu the field of reductive C - C bond formation after epoxide opening via electron transfer has developed at a rapid pace. Novel catalytic methodology, enantio- and stereoselective synthesis and numerous applications in the preparation of biologically active substances and natural products have evolved. In brief, a large repertoire of useful and original reactions is available. These reactions are waiting to be applied in a complex context ... 

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