ABSTRACT
Two complementary strategies for the synthesis of febrifugine are detailed based on previously developed chemoenzymatic approaches to the 3-hydroxypiperidine skeleton. The introduction of the quinazolone-containing side chain in both strategies was based on an N-acyliminium ion-mediated coupling reaction.
Subject(s)
Piperidines/chemical synthesis , Quinazolines/chemical synthesis , Catalysis , Piperidines/chemistry , Quinazolines/chemistry , Stereoisomerism , Substrate SpecificityABSTRACT
A stereoselective synthesis of (+)-epiquinamide is presented in combination with determination of the absolute configuration of the natural product. Key steps in the sequence involved chemoenzymatic formation of an enantiomerically pure cyanohydrin, reductive cyclization to the corresponding cyclic N,N-acetal, and subsequent conversion into a suitable N-acyliminium ion precursor to enable construction of the second ring.
Subject(s)
Acetals/chemistry , Cations/chemistry , Imines/chemistry , Quinolizines/chemical synthesis , Animals , Anura , Biological Products/chemical synthesis , Biological Products/chemistry , Quinolizines/chemistry , Stereoisomerism , Substrate SpecificityABSTRACT
The nitrile hydrolyzing properties of the bacterium strain Rhodococcus erythropolis NCIMB 11540 have been investigated. Using whole cells of the microorganism, a wide variety of aromatic and aliphatic cyanide-containing substrates was successfully hydrolyzed to the corresponding amide or acid. In the case of dicyanides, selective monohydrolysis took place, which was further explored in the desymmetrization of malononitriles resulting in the corresponding cyano amides in enantiomeric excesses of up to 98%.
