To optically pure synthons for

Economic Perspectives of Biocatalytic Conversion of Aromatics to Optical Pure Synthons for the Pharmaceutical Industry... 

Antibody catalysts, role in environmentally benign synthesis of chemicals, 125-126 Aqueous-supercritical carbon dioxide medium, phase-transfer catalytic oxidation, 144-145 Arene cw-dihydrodiols, biocatalytic conversion of aromatics to optically pure synthons for pharmaceutical industry, 180-195... 

The aim of this article is to focus on the diversity of aldonolactones as chiral synthons. The chemistry of aldonolactones was an almost unexplored area when, in 1979, we started our investigations on the reaction of aldonolactones with hydrogen bromide in acetic acid thereby obtaining bromodeoxyaldonolac-tones [1,2]. These compounds have over the years proven to be very versatile compounds for stereoselective synthesis, both in the carbohydrate field, giving access to otherwise less readily obtainable sugars, and as chiral, optically pure synthons in a broader sense within organic chemistry. 

Utilization of the optically pure compounds for the construction of optically active material is exemplified with the preparation of A-ring precursor 218 from alcohol (/ )-(+)-215, which reacts to form cyclopropane compound 217, which is then desilylated to A-ring synthon 218. 

The hydrolysis of racemic non-natural amides has led to useful products and intermediates for the fine chemical industry. Thus hydrolysis of the racemic amide (2) with an acylase in Rhodococcus erythrolpolis furnished the (S)-acid (the anti-inflammatory agent Naproxen) in 42 % yield and > 99 % enantiomeric excess1201. Obtaining the 7-lactam (—)-(3) has been the subject of much research and development effort, since the compound is a very versatile synthon for the production of carbocyclic nucleosides. An acylase from Comamonas acidovor-ans has been isolated, cloned and overexpressed. The acylase tolerates a 500 g/ litre input of racemic lactam, hydrolyses only the (+)-enantiomer leaving the desired intermediate essentially optically pure (E > 400)[211. 

J )-Mandelic acid 3 is a useful chiral synthon for the production of pharmaceuticals such as semi-synthetic penecillins, cephalosporins and antiobesity agents and many methods have been reported for the preparation of the optically pure material. A method to deracemize the racemate which is readily available on a large scale was developed by Ohta et al. using a combination of two biotransformations. The method consists of enantioselective oxidation of (S)-... 

Steroid synthesis. The sulfoxide (S)-( + )-2 has been used as a chiral synthon for ring D in steroid synthesis. The first step in a synthesis of 11-ketoequilenin (5)3 involves addition of 6-methoxy-2-naphthylmagnesium bromide followed by in situ methylation of the intermediate enolate ion to give 3 in greater than 98% optical purity. This product was converted into optically pure (S, S)-( + )-4, the racemate of which has been converted into( + )-l 1-kctoequilenin. 

As a part of ongoing efforts to synthesize a potent, orally active anti-platelet agent, xemilofiban 1 [1], development of an efficient chemoenzymatic process for 2, the chiral yS-amino acid ester synthon (Fig. 1) was proposed. The scheme emphasized the creation of the stereogenic center as the key step. In parallel with the enzymatic approach, chemical synthesis of the / -amino acid ester synthon emphasized formation of a chiral imine, nucleophilic addition of the Reformatsky reagent, and oxidative removal of the chiral auxiliary. This chapter describes a selective amida-tion/amide hydrolysis using the enzyme Penicillin G amidohydrolase from E. coli to synthesize (R)- and (S)-enantiomers of ethyl 3-amino-5-(trimethylsilyl)-4-pen-tynoate in an optically pure form. The design of the experimental approach was applied in order to optimize the critical reaction parameters to control the stereoselectivity of the enzyme Penicillin G amidohydrolase. 

Having completed the synthesis of the optically pure AB ring synthon (- )-153, the authors turned their attention to the allylic bromide 163, a synthon for rings D and E of 3-amyrin. 

After their utilization as plastic items, PHAs can not only be composted, but can also be easily depolymerized to a valuable source of optically pure R-(-)-configured bifunctional hydroxy acids which are of interest as synthons for chiral high-value chemicals such as vitamins, antibiotics, pheromones and aromatics (Ren et al. 2005). Some of these acids also exhibit important biological properties such as antimicrobial and antiviral activity (Ruth et al. 2007). 

The use of sulfoxides as chiral synthons has, over recent years, become a highly dependable protocol in synthetic organic chemistry. To some extent, however, the use of sulfoxides in asymmetric synthesis has been limited by the lack of a reliable and general method for their preparation in optically pure form. In this review we present the development of chiral sulfoxide synthesis via nucleophilic displacement at sulfur from the pioneering work of Andersen in 1962 to more recent methods. Sulfoxides have become associated with many diverse areas of synthetic chemistry indeed, their ability to act as a handle for the stereoselective generation of chirality at proximate centres has attracted much research worldwide. 

Several groups in the United Kingdom and two in the United States began to exploit the asymmetric features of these diverse and potentially valuable synthons in synthesis. A look at a general design for entire classes of compounds from the simple, optically pure materials provided by the enzymes make the advantages of a chemoenzymatic approach to the preparation of complex molecules clear. 

However, it should be noted that the concept of carbohydrates as chiral synthons has always fascinated sugar chemists as the excellent 1972 review by Inch will attest 42). Thus in order to preserve historical perspective three antecedents for the use of sugars in asymmetric syntheses are noted in Scheme 1. First is Wolfrom s proof of the structure of (-t-)-alanine by synthesis from D-glucosamine 102). Second is the synthesis of the optically pure mandelic acid derivatives from 2,3-4,5-di-O-isopropylidene-fl/tfeAy o-D-arabinose (1) by Bonner (9), and third is Lemieux s synthesis of ethanol-l-d from diacetone glucose (6 a, Scheme 2) via the deuterated xylose (2) (57). 

There has been a further report on the use of optically-pure (61), prepared emqmiically, to make carbanucleosldes, (-)-carbocyclic-ddT and (-)-carbocyclic-2, 3 -dideoxy-3 -fluorothymidlne being the targets thus prepared. A synthon for carbocycUc -nucleosides, previously available as a racemate (Vol.20, p.214. Scheme 16), has now been made in chiral form by use of a di-l-menthyl ester as a chiral auxiliary. 

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