Meso intermediates, natural products synthesis

The chiral (salen)Co catalysts have also been applied to cyclization reaction and preparation of intermediates for natural product synthesis [85]. In addition, chiral (salen)Ru catalysts proved to be effective for kinetic resolution of racemic epoxides [86]. Tridentate Schiff base Cr(III) complex (201) derived l-amino-2-indanol acts as a potent catalyst for asymmetric ring-opening reaction of meso-aziridines with trimethylsilyl azide (Scheme 16.60) [87]. The aziridine (200) was readily converted at —30 °C to the corresponding amino-azide in 95% yield with 94% ee. 

This chapter illustrates the application of lipases and esterases as user-friendly biocatalysts in (i) desymmetrization of prochiral or meso-diols and diacetates, (ii) kinetic resolution of racemic alcohols, and (iii) preparation of enantiopure intermediate(s) from a mixture of stereoisomers by enzymatic differentiation. All the examples were taken from our own works in natural products synthesis. 

PLE catalyzes the hydrolysis of a wide range of meso-diesters (Table 2). This reaction is interesting from both theoretical and practical standpoints. Indeed, the analysis of a large range of kinetic data provided sufficient information to create a detailed active site model of PLE (31). From a practical standpoint, selective hydrolysis of y j (9-cyclo-I,2-dicarboxylates leads to chiral synthons that are valuable intermediates for the synthesis of a variety of natural products. 

Enantiomerically pure cyclopropanes are a frequent motif in the structure of natural products. Their synthesis is often demanding and many approaches have been made [50, 51]. Porcine pancreatic lipase (PPL) was used for the stereoselective desymmetrization of a cyclopropane dibutanoate (Fig. 2). The asymmetric hydrolysis of the meso compound yielded the corresponding enantiopure alcohol almost quantitatively. The intermediate obtained was successfully applied in the total synthesis of dictyopterenes A and C, sexual pheromones of brown algae [52], and constanolactones (see below) [53]. 

This collection begins with a series of three procedures illustrating important new methods for preparation of enantiomerically pure substances via asymmetric catalysis. The preparation of 3-[(1S)-1,2-DIHYDROXYETHYL]-1,5-DIHYDRO-3H-2.4-BENZODIOXEPINE describes, in detail, the use of dihydroquinidine 9-0-(9 -phenanthryl) ether as a chiral ligand in the asymmetric dihydroxylation reaction which is broadly applicable for the preparation of chiral dlols from monosubstituted olefins. The product, an acetal of (S)-glyceralcfehyde, is itself a potentially valuable synthetic intermediate. The assembly of a chiral rhodium catalyst from methyl 2-pyrrolidone 5(R)-carboxylate and its use in the intramolecular asymmetric cyclopropanation of an allyl diazoacetate is illustrated in the preparation of (1R.5S)-()-6,6-DIMETHYL-3-OXABICYCLO[3.1. OJHEXAN-2-ONE. Another important general method for asymmetric synthesis involves the desymmetrization of bifunctional meso compounds as is described for the enantioselective enzymatic hydrolysis of cis-3,5-diacetoxycyclopentene to (1R,4S)-(+)-4-HYDROXY-2-CYCLOPENTENYL ACETATE. This intermediate is especially valuable as a precursor of both antipodes (4R) (+)- and (4S)-(-)-tert-BUTYLDIMETHYLSILOXY-2-CYCLOPENTEN-1-ONE, important intermediates in the synthesis of enantiomerically pure prostanoid derivatives and other classes of natural substances, whose preparation is detailed in accompanying procedures. 

Its striking total synthesis was however accompUshed by Overman et al. by following a different route (Scheme 7.27) [76]. meso-Chimonantine (123), a natural product by itself, was chosen as a starting point as it aheady contains two of the pyrroUdinoindoline units of target compound 121. Starting from commercially available oxindole and isatin, mexo-chimonantine had been synthesized previously in the Overman laboratories in a stereocontrolled 13-step procedure [77]. Now, four additional steps were necessary to access the central intermediate for the... 

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