Current Organic Chemistry - Volume 6, Issue 5, 2002

An increasingly large number of bioactive cyclic peptides have been found in nature. The enhanced biological specificity, activity, and metabolic stability of cyclopeptides, by virtue of their conformationally constrained structural feature, have attracted much attention and made these compounds extensively studied. Cyclic peptidomimetic scaffolds and templates have been widely used to assemble various spatially defined functional groups for molecular recognition and drug discovery. These efforts are complemented optimally by NMR and X-ray based structure information, and assisted by molecular modeling based structure predictive methods. Peptide cyclization also becomes an effective and commonly employed strategy for peptide modifications. During the past several decades, great effort has been made to develop more efficient methods for the synthesis of cyclic peptides and peptidomimetics, as potential drug leads and / or as models for conformational analysis. This review is aimed at highlighting novel recently developed peptide cyclization approaches, and illustrating the profitable applications.

After introducing chirality with the winding columns of baroque altars and snail shells, the enantioselective hydrogenation of dehydroamino acids is described. Then, the enantioselective homo Diels-Alder reaction of norbornadiene with phenylacetylene is presented, which leads to 8-phenyldeltacyclene in almost enantiomerically pure form. Its reaction with 1,2-bisphosphanylbenzene affords P,P,P'-tris(9-phenyldeltacyclan-8-yl)-1,2-bisphosphanylbenzene, a chelate ligand with 3 chiral deltacyclanyl substituents and a PH bond, comprising 24 asymmetric carbon atoms of a given configuration and a stereogenic secondary phosphorus atom. This chelate ligand forms mononuclear, phosphido-bridged dinuclear and - most unusual - trinuclear Ni, Pd and Pt complexes. The trinuclear complexes consisting of three joint square planar units are unique in Ni, Pd and Pt chemistry.

It is well recognized that biocatalysis is of special relevance in organic synthesis. Among the enzymes used, lipases have demonstrated a great versatility in enzymatic hydrolysis, transesterification, or aminolysis reactions. Other biocatalysts, such as oxidoreductases and some liases, are also of interest for organic chemists to synthesize compounds that are difficult to obtain by classical chemical procedures. Recently, biotransformations have shown their utility in natural products synthesis, such as in carbohydrates, steroids and nucleosides. Vitamin D, through its hormonally active form 1α,25-dihydroxyvitamin D3, plays an important role in the endocrine system. This metabolite exhibits a much broader spectrum of biological activities than expected. As a result, considerable effort has been made toward the synthesis of structurally related congeners that show interesting pharmacological applications. Most of the analogues prepared have modifications on the upper side chain, more accessible from a synthetic point of view. However, the enzymatic methodology can simplified the chemical routes allowing the synthesis of adequate precursors in a most simple way. We review here, the utility of biotransformations for the preparation of new Vitamin D analogues using different kind of biocatalysts.

Disaccharide and oligosaccharide mimics are potentially more selective glycosidases inhibitors than simple monosaccharide mimics. They represent also more selective ligands for lectins and oligosaccharide receptors and can become immunostimulating agents. The biological properties of disaccharide and oligosaccharide analogs containing thiosugars (5-thiopyranoses, 4-thiofuranoses) are revised together with the methods for their obtention.