Enzymatic Oxidation Chemistry

Abstract

Previously, we reported a general method for the chemo-enzymatic deracemization of primary, 1 secondary 2 and tertiary 3 amines in high yield and enantiomeric excess. The deracemization process involves a two-step, one-pot reaction and employs an enantioselective amine oxidase (MAO-N) in combination with a nonselective chemical reducing agent (Figure 11.1). We have further demonstrated the utility of this variant enzyme by way of the asymmetric synthesis of the natural product (þ)-crispine A in 97 % ee. 4 The previously reported MAO-N-D5 variant, which contains five important mutations (Ile246Met/Asn336Ser/Met348Lys/ Thr384Asn/Asp385Ser) was used; its preparation has been described previously. 5,6 R 3 R 4 N R 3 R 4 N R 3 R 4 N + NH 3 :BH 3 enantio selective amine oxidase R 1 R 2 R 1 R 2 R 1 R 2 (S) (R) Figure 11.1 Enzymatic deracemization of racemic amines via a two-step, one-pot process utilizing an enantioselective amine oxidase in combination with ammonia-borane. Practical Methods for Biocatalysis and BiotransformationsEdited

Concise Enantiospecific, Stereoselective Syntheses of (+)-Crispine A and Its (−)-Antipode

“…Similarly, the cis isomer (5 S ,10b S )- 7a , the major adduct from the Pictet−Spengler cyclization, was converted to the methylselenyl ester (5 S ,10b S )- 12 as shown in Scheme . As with the regioisomer (5 S ,10b R )- 11 , the radical decarboxylation protocol transformed (5 S ,10b S )- 12 to the unnatural antipode of crispine A [( S )-(−)- 1 ] , in 39% isolated yield for the two-step process. The alkaloid enantiomer ( S )- 1 was found to rotate polarized light in an equal but opposite manner to ( R )- 1 and was also shown to be a single isomer by chiral HPLC analysis (see Supporting Information).…”

“…Interestingly, synthetic reports of this heterocycle can also be found in the literature prior to its identification as a natural product extract or its naming as crispine A . A number of directed enantioselective syntheses of this alkaloid have also recently appeared in the literature, along with asymmetric preparations of the ( S ) antipode as well as crispine A analogues . We nevertheless sought to contribute our own novel asymmetric approach based on a Pictet−Spengler bis-cyclization reaction between enantiopure methoxytyrosine derivatives and an acetal bearing a tethered terminal leaving group.…”