Current Organic Chemistry - Volume 5, Issue 4, 2001

In this review we have sought to give the reader an appreciation of the many synthetic applications now known for the more popular asymmetric (3,3)sigmatropic rearrangements. The ability to predict the stereochemical outcome of the rearrangements, and the ability to prepare products containing several contiguous chiral centres makes the application of such asymmetric rearrangements an attractive proposition to the synthetic chemist.We, and others, have begun to develop the amino-Cope rearrangement as a new synthetic protocol that appears to have much untapped potential. The question of the whether the rearrangement proceeds via a stepwise or concerted mechanism, and if the mechanistic pathway can be controlled, remains to be established. Current work in our group is aimed at applying the asymmetric amino-Cope rearrangement in synthetically useful procedures, for example in the synthesis of highly functionalised oxygen and nitrogen heterocycles. Our progress in this area will be reported in due course.

The beeta-turn is a common recognition feature between peptide ligands and their macromolecular targets. The cyclization of a short peptide segment with a linker is one method of imitating this conformation. The first part of this review discusses tethering strategies which have resulted in the development of mimetics for the enkephalins and somatostatin as well as in the discovery of antagonists for targets such as thrombin, the CD4 protein on T lymphocytes, the integrins, and other receptors involved in inflammatory diseases. The second portion of this review describes the application of e-aminocaproic acid (Aca) as a tether in cyclic peptide beeta-turn mimics. Alkyl substituents on Aca may influence the b-turn preference of the dipeptide. The synthesis of the substituted Aca linkers and their incorporation into the macrocycles is highlighted.

Filamentous fungi are capable of catalyzing regio- and stereoselective hydroxylation on an extensive array of natural and synthetic hydrophobic organic substrates. A significant benefit of fungal hydroxylation is that non-activated carbon centers can be functionalized in ways that may not be easily emulated by classical organic means. The enzymes thought to perform the hydroxylations are cytochrome P450 monooxygenases. This review presents the evidence for the role of cytochrome P450s and summarizes the broad spectrum of substrates hydroxylated by various filamentous fungi in the twenty years prior to August 2000. Whole cell systems are generally preferred because monooxygenases that catalyze these reactions have not been isolated and characterized. Optimization of the hydroxylation conditions and the ability to accurately predict the biotransformation product(s) are necessary future developments before widespread synthetic practicality is achieved. Several recent developments in optimization techniques are also discussed including the use of protecting groups, varied experimental conditions, and the use of additives to the whole cell systems.