In this tutorial review directed towards chemists interested in synthesis or catalysis, the application of gold catalysis in total synthesis is summarised and the mode of activation of the substrate by the gold catalyst is discussed.

Gold catalysis in total synthesis.

The Synthesis of Vicinal Amino Alcohols

Catalytic Asymmetric Synthesis of α-Amino Acids

The sphingolipid bases, D-erythro- and D-threo-sphingosines, are the target molecules that have been synthesized to demonstrate the efficiency of a new methodology to control both absolute and relative configurations in acyclic systems. Tubulysins are compounds of extraordinary potency, rapidly degrading the tubulin cytoskeleton, with tubulysin D being the most active tubulin-modifier known so far. Among other isonitriles, isocyanoacetate derivatives occupy an important place in the field of synthetic application and reaction diversity, which makes them strongly attractive objects for investigation. The unique multifunctional nature of isocyanoacetic acid derivatives opens up a range of exciting reactions, especially tandem/cascade processes for the synthesis of complex cyclic and macrocyclic systems. Multicomponent chemistry of isocyanoacetates is also a powerful instrument to access different classes of biochemically relevant compounds such as peptides, peptide molecules, and nitrogen heterocycles.

Isocyanoacetate derivatives: synthesis, reactivity, and application.

This Review describes singlet oxygen (1O2) in the organic synthesis of targets on possible 1O2 biosynthetic routes. The visible-light sensitized production of 1O2 is not only useful for synthesis; it is extremely common in nature. This Review is intended to draw a logical link between flow and batch reactions—a combination that leads to the current state of 1O2 in synthesis.

Using Singlet Oxygen to Synthesize Natural Products and Drugs

(-)-Balanol, a fungal metabolite with potent protein kinase C inhibitory properties, has been prepared in a total synthesis which makes use of an anionic homo-Fries rearrangement approach to the benzophenone subunit and in which the azepane subunit is obtained from (2S,3R)-3-hydroxyly- sine

Total Synthesis of (-)-Balanol

Two total syntheses of the potent protein kinase C inhibitory fungal metabolite balanol are described In the first approach, the core aminohydroxyazepane subunit was prepared in racemic form by stereospecific functionalization of N-benzyl-e-caprolactam Resolution prior to coupling to the benzophenone subunit provided access to both enantiomers of balanol In the second approach, an efficient silicon-mediated cyclization of (2S,3R)-3-hydroxylysine followed by reduction provided the azepane subunit in enantiomerically pure form The sterically congested benzophenone subunit was assembled from two highly substituted aromatic precursors by way of an anionic homo-Fries rearrangement

Total Synthesis of (-)- and (+)-Balanol(1).

Two efficient chiral syntheses of 3-hydroxylysine, a naturally occurring amino acid and a putative intermediate in the synthesis of balanol, a potent protein kinase C inhibitor, are described. The synthesis of (2R,3S)-3-hydroxylysine utilizes Hayashi's chiral ferroceno gold catalyst. The synthesis of (2S,3R)-3-hydroxylysine demonstrates a β-hydroxy amino acid synthesis with the chirality derived from the Sharpless chiral cis-hydroxylation

Two Chiral Syntheses of threo-3-Hydroxylsine

Two total syntheses of the potent protein kinase C inhibitory fungal metabolite balanol are described. In the first approach, the core aminohydroxyazepane subunit was prepared in racemic form by stereospecific functionalization of N-benzyl-epsilon-caprolactam. Resolution prior to coupling to the benzophenone subunit provided access to both enantiomers of balanol. In the second approach, an efficient silicon-mediated cyclization of (2S,3R)-3-hydroxylysine followed by reduction provided the azepane subunit in enantiomerically pure form. The sterically congested benzophenone subunit was assembled from two highly substituted aromatic precursors by way of an anionic homo-Fries rearrangement.

Shelley H. Smith

Papers

Total Synthesis of (-)-Balanol

Total Synthesis of (-)- and (+)-Balanol(1).

Two Chiral Syntheses of threo-3-Hydroxylsine

Total Synthesis of (-)- and (+)-Balanol.

Two Chiral Syntheses of threo-3-Hydroxylysine.