Controlling stereoselectivity by enzymatic and chemical means to access enantiomerically pure (1S,3R)-1-benzyl-2,3-dimethyl-1,2,3,4-tetrahydroisoquinoline derivatives

A chemoenzymatic strategy for the synthesis of enantiomerically pure novel alkaloids (1S,3R)- 1-benzyl-2,3-dimethyl-1,2,3,4-tetrahydroisoquinolines is presented. The key steps are the biocatalytic stereoselective reductive amination of substituted 1-phenylpropan-2-one derivatives to yield chiral amines employing microbial x-transaminases, and the diastereoselective reduction of a Bischler– Napieralski imine intermediate by catalytic hydrogenation in the presence of palladium on charcoal, leading exclusively to the desired cis-isomerFil: Orden, Alejandro Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto de Investigaciones en Tecnología Química; Argentina;Fil: Schrittwieser, Joerg H.. University of Graz. Department of Chemistry, Organic and Bioorganic Chemistry; Austria;Fil: Resch, Verena. University of Graz. Department of Chemistry, Organic and Bioorganic Chemistry; Austria;Fil: Mutti, Francesco G.. University of Graz. Department of Chemistry, Organic and Bioorganic Chemistry; Austria;Fil: Kroutil, Wolfgang. University of Graz. Department of Chemistry, Organic and Bioorganic Chemistry; Austria

Stereoselective synthesis of γ-hydroxynorvaline through combination of organo- and biocatalysis

An efficient route for the synthesis of all four diastereomers of PMP-protected α-amino-γ-butyrolacton to access γ-hydroxynorvaline was established. The asymmetric key steps comprise an organocatalytic Mannich reaction and an enzymatic ketone reduction. Three reaction steps could be integrated in a one-pot process, using 2-PrOH both as solvent and as reducing agent. The sequential construction of stereogenic centres gave access to each of the four stereoisomers in high yield and with excellent stereocontrol

(Chemo)enzymatic cascades - Nature's synthetic strategy transferred to the laboratory

The astonishing efficiency with which living organisms build complex molecules from simple starting materials has inspired chemists for centuries. Among the synthetic strategies that nature uses to achieve this efficiency, the combination of several enzymatic transformations in cascading sequences is of outstanding importance. With the rise of biocatalysis, researchers now have the tools at hand to mimic this strategy and develop artificial enzyme cascades of impressive complexity. This editorial review aims to introduce the reader to some key aspects of (chemo)enzymatic cascades, as well as to put the submissions to the present Special Issue into a broader context

Simultaneous iridium catalysed oxidation and enzymatic reduction employing orthogonal reagents

An iridium catalysed oxidation was coupled concurrently to an asymmetric biocatalytic reduction in one-pot; thus it was shown for the first time that iridium- and alcohol dehydrogenase-catalysed redox reactions are compatible. As a model system racemic chlorohydrins were transformed to enantioenriched chlorohydrins via an oxidation–asymmetric reduction sequence.

Biocatalytic Organic Synthesis of Optically Pure (S)-Scoulerine and Berbine and Benzylisoquinoline Alkaloids

A chemoenzymatic approach for the asymmetric total synthesis of the title compounds is described that employs an enantioselective oxidative CC bond formation catalyzed by berberine bridge enzyme (BBE) in the asymmetric key step. This unique reaction yielded enantiomerically pure (R)-benzylisoquinoline derivatives and (S)-berbines such as the natural product (S)-scoulerine, a sedative and muscle relaxing agent. The racemic substrates rac-1 required for the biotransformation were prepared in 48 linear steps using either a BischlerNapieralski cyclization or a C1C alkylation approach. The chemoenzymatic synthesis was applied to the preparation of fourteen enantiomerically pure alkaloids, including the natural products (S)-scoulerine and (R)-reticuline, and gave overall yields of up to 20% over 59 linear steps

Biocatalytic Organic Synthesis of Optically Pure (<i>S</i>)-Scoulerine and Berbine and Benzylisoquinoline Alkaloids

A chemoenzymatic approach for the asymmetric total synthesis of the title compounds is described that employs an enantioselective oxidative C–C bond formation catalyzed by berberine bridge enzyme (BBE) in the asymmetric key step. This unique reaction yielded enantiomerically pure (<i>R</i>)-benzylisoquinoline derivatives and (<i>S</i>)-berbines such as the natural product (<i>S</i>)-scoulerine, a sedative and muscle relaxing agent. The racemic substrates <i>rac</i>-<b>1</b> required for the biotransformation were prepared in 4–8 linear steps using either a Bischler–Napieralski cyclization or a C1–Cα alkylation approach. The chemoenzymatic synthesis was applied to the preparation of fourteen enantiomerically pure alkaloids, including the natural products (<i>S</i>)-scoulerine and (<i>R</i>)-reticuline, and gave overall yields of up to 20% over 5–9 linear steps

Access to Lactone Building Blocks via Horse Liver Alcohol Dehydrogenase-Catalyzed Oxidative Lactonization

The oxidative lactonization of 1,4-, 1,5-, and 1,6-diols using horse liver alcohol dehydrogenase (HLADH) is reported. Molecular oxygen was used as terminal electron acceptor by utilization of the laccase-mediator concept to regenerate the oxidized nicotinamide cofactor and producing water as sole byproduct. Spontaneous hydrolysis of the lactone products was identified as a major limiting factor toward preparative application of the system, which can be alleviated by using a two liquid phase approach to extracting the product into an organic solvent