The Synthesis of Vicinal Amino Alcohols

Structures of Five Antibiotics Bound at the Peptidyl Transferase Center of the Large Ribosomal Subunit

1,2-Amino alcohols are high-value, versatile functional groups that are found in scores of biologically active molecules and other interesting synthetic targets such as ligands and auxiliaries. Given their prominent position within organic compounds of import, it is no surprise to note that many routes have been developed to access this motif and there are many different starting points from which a synthetic chemist might embark on a synthesis. However, one particular approach stands out from the others, and this is the direct conversion of an alkene to a vicinal amino alcohol derivative (oxyamination). Research in this field has been particularly active in recent years and many interesting new methodologies have been reported. The purpose of this review is to give the reader a tour of the methods that have emerged in the last few years so one can appreciate the myriad of different metals and reagents that can accomplish the oxyamination of alkenes. There are still many challenges to be overcome and, herein, we also outline the areas that are ripe for further development and which bode well for the future.

Recent developments in methodology for the direct oxyamination of olefins.

Proton transfer and hydrogen bonding are two aspects of the chemistry of hydrogen that respectively govern the behaviour and structure of many molecules, both simple and complex, from water to DNA. The β-dicarbonyls exhibit both of these features, and in ways which have singled them out for detailed study for many years. They provide the best known examples of keto ⇆ enol tautomerism, with the advantage of slow proton transfer and high concentrations of the enol tautomers in most cases. These enols are stabilized by intramolecular OHO hydrogen bonds which at various times have been thought of as being centred, linear hydrogen bonds that are somehow incorporated into the delocalised π system to give “aromatic” systems. Research involving structural, spectroscopic and computational techniques has deepened our understanding of these compounds and changed our picture of them. The hydrogen bonding is surprisingly strong, surprising since it is neither centred, nor linear, nor involved in the ring’s delocalized bonding, although it is certainly coupled to it. This review deals with controversies that have surrounded the β-dicarbonyls and discusses the current view that the enol tautomers are a double-minimum potential well with a low energy barrier. The review ends with a brief look at the β-thioxoketones, which provide an analogous system based on a heteronuclear SHO hydrogen bond in the enol or enethiol tautomer.

The composition, structure and hydrogen bonding of the β-diketones

To investigate the mechanism which controls the onset of DNA synthesis, we examined the regulation of thymidine kinase (TK) and its mRNA in the cell cycle. TK activity provides a useful marker for the onset of the S phase in mammalian cells. The present analysis of regulation of TK mRNA in BALB/c 3T3 cells showed that (i) the increase in TK activity depended on the availability of TK mRNA, (ii) the level of TK mRNA between G0 and S increased more than 20-fold, (iii) the rate of run-on TK transcription increased at most 2- to 4-fold between the G0 and S phases, (iv) the half-life of TK mRNA was greater than 8 to 12 h in the S and M phases and decreased as cells entered quiescence, (v) the TK mRNA increase was fully blocked by inhibition of protein synthesis by only 60%, (vi) this inhibition was completely effective for up to about 10 h following serum addition and progressively much less effective when the drugs were added later. These results suggest that the appearance of TK mRNA at the beginning of the S phase in serum-stimulated 3T3 cells is controlled not only by the rate of gene transcription but importantly also by the decreased rate of mRNA degradation. Similar mechanisms may be involved in regulation of the onset of DNA synthesis and the increase in TK mRNA since both are controlled in a manner consistent with a requirement for a labile protein.

Control of thymidine kinase mRNA during the cell cycle.

Structure of anisomycin.

A three-dimensional X-ray-diffraction analysis of tetra-acetylethane has been carried out. The crystal are orthorhombic, space group Pbcn, with a= 9·18, b= 9·42, c= 11·66 A, Z= 4. The molecule exists in the dienolic form in the crystal. It has crystallographic symmetry 2 (C2) but, in fact, approximates closely to 2m(D2d), consisting of two substantially planar halves twisted through almost 90° with respect to each other. Each half contains a short and, probably, symmetrical hydrogen bond. The bond lengths and angles are compared with those in a number of metal acetylacetonates, and close similarities are traced.

Peter J. Wheatley

Papers

Structure of anisomycin.

The crystal and molecular structure of tetra-acetylethane

The structure of anisomycin