The reactivity features of photochemically and chemically generated reactive species from organometallic compounds and their applications in organic synthesis are described. The reactive species include exciplexes, radical ions, and radicals involving group 14 organometallic compounds, and also iron complexes generated from Fe₃ (CO) ₁₂ and Bu₄NFe(CO)₃NO. By utilizing the specific chemical properties of these reactive species, a variety of new, highly selective synthetic reactions have been developed. The typical examples of the developed reactions are as follows : 1) synthesis of Si-and Ge-containing spiro and cyclophane compounds, 2) photo-allyl and arylmethylation of aromatic nitriles, 3) photo-allylation and silylation of electron-deficient alkenes, 4) double vicinal C-C bond formation on electron-deficient alkenes, 5) cyclodimerization of α, β-unsaturated carbonyl compounds, 6) pyrrole formation via reductive deoxygenation of dihydro-1, 2-oxazines, 7) regioselective nucleophilic and electrophilic addition to the allylic ligands of (η³-allylic) Fe (CO)₂NO complexes, and 8) 1, 4-functionalization of 1, 3-dienes. The methods for enhancing the efficiencies and selectivities of photoreactions involving electron-transfer are also described.

View full abstract

There are two difficulties for peripherally administered peptides to display their activities in central nervous system (CNS). First, a small amount of peptide is easily inactivated by peptidases present in blood and peripheral tissues. Second, peptides that do reach CNS are also digested by proteases in CNS before binding to their specific receptors. Dynorphin-A was degraded by incubation with mouse serum and mouse brain homogenates at 37°C in the presence or absence of protease inhibitors which were used to prevent secondary degradation of fragments. With the basic knowledge of the enzyme-susceptible sites of dynorphin-A, structure-activity relationships were studied so that we were able to reach the metabolically stable analogue (E-2078) whose structure is (N-MeTyr¹, N-MeArg⁷, D-Leu⁸) dynorphin-A (1-8) ethylamide. This compound showed stronger analgesic activity than morphine by peripheral administration and was successfully massproduced by the development of the new deblocking method.

View full abstract

This review deals with the chemistry of aspartic acid derivatives and its utilization for drug-syntheses. It should be noted in particular that “Aspartylation”, in which the aspartic acid skeleton is introduced into the target molecules by the use of various aspartic acid synthons, provides a useful methodology for the prepara-tion of the pharmaceuticals.

View full abstract

The interest in the synthetic reactions by enzymes in organic solvents is growing rapidly. There are many advantages in employing enzymes in organic solvents, such as the increase in solubility of nonpolar substrates and the shift of thermodynamic equilibria to favor synthesis over hydrolysis : This paper reviews the recent advance in the synthesis of esters and peptides by proteases in hydro-organic reaction systems. Attention is paid to the characteristics of the reactions in hydrophilic and hydrophobic solvents, and also to the changes in the activity and specificity of the proteases as compared to the reactions in aqueous solutions. The effects of immobilization and the chemical modification of the enzymes on the reactions in organic solvents are also described.

View full abstract

New NADPH-dependent carbonyl reductases which catalyze stereospecific reductions of carbonyl compounds have been purified from various microorgansms and characterized. The enzymes “polyketone reductase” from Candida parapsilosis and Mucor ambiguus specifically catalyze reduction of various prochiral cyclic diketones, yielding the corresponding (R)- and (S)-hydroxyketones, respectively. Aldehyde reductase from Sporobolomyces salmonicolor and carbonyl reductase from C. macedoniensis catalyze stereospecific reduction of various aliphatic and aromatic ketones and aldehyds. Ketopantoic acid reductase from Pseudomonas maltophilia and an FMN-dependent alcohol dehydrogenase from Nocardia asteroides, catalyze reduction of ketopantoic acid to _D-pantoic acid and oxidation of _L-pantoyl lactone to ketopantoyl lactone. These enzymes were successfully applied to the synthesis of chiral intermediates for the synthesis of _D-pantothenic acid and _L-carnitine.

View full abstract