Teicoplanin applications

The most prominent application of the Ru-arene chemistry has been for the preparation of biaryl ethers in the syntheses of portions of vancomycin,467 ristocetin (Equation (127)),462,468-473 and teicoplanin (see also Section 10.14.1.2).474-476 Additional applications477-479 have included the syntheses of the macrocyclic biaryl ether-containing compounds K-13480,481 and OF4949-III,481,482 several macrocyclic depsipeptides,483,484 and poly(phenylene oxide) polymers.485... 

Cyclic amines (including local anesthetic drugs) and amides were among the first classes of chiral compounds investigated in the early stages of the application of macrocyclic antibiotics as chiral selectors therefore, they were screened on vancomycin [7], teicoplanin [30], and ristocetin A [33] CSPs, under RPmode systems. Cyclic imides (including barbiturates, piperidine-2,6-diones, and mephenytoin) have been separated on a vancomycin CSP [157], under NP and RP mobile phase conditions. 

Table 4 lists some representative examples of macrocyclization via the intramolecular SNAr reaction. In addition to the 14- and 17-membered cycloisodityrosines shown in the table, a variety of mono-, bi-, and tricyclic systems from the vancomycin family of natural products including the orienticin C/40 vancomycin J44-47 and teicoplanin[48 aglycons have been prepared by this method.This versatility, coupled with the high yields obtained, makes the intramolecular SNAr reaction currently the most widely applicable method for cycloisodi-tyrosine formation. 

The application of antibiotics as chiral selectors has resulted in the successful resolution of almost all types of neutral, acidic, and basic racemic molecule. These antibiotics have been used for the enantiomeric resolution of amino acids, their derivatives, peptides, alcohols, and other pharmaceuticals. The selectivities of the most commonly used antibiotic-based (vancomycin, teicoplanin, and ristocetin A) CSPs varied from one racemate to another and are given in Table 1. Vancomycin was used for the chiral resolution of amino acids, amines, amides, imides, cyclic amines, amino alcohols, hydantoins, barbiturates, oxazolidinones, acids, profens, and other pharmaceuticals. Teicoplanin was found to be excellent chiral selector for the enantiomeric resolution of amino acids, amino alcohols, imides, peptides, hydantoins, a-hydroxy and halo acids, and oxazolidinones, whereas ristocetin A is capable of chiral resolution of amino acids, imides, amino... 

Macrocyclic antibiotics such as teicoplanin and vancomycin have been used in chiral stationary phases separations of amino acids, drugs, and other species using HPLC and other separations methods. These applications have been reviewed in a number of recent sources, including a 2004 monograph on chiral separations. [97, 101-107]... 

Since first demonstration in 1994 of the potential use of macrocyclic antibiotics as chiral selectors in analysis, glycopeptide antibiotics have been successfully applied for enantiomer separations by liquid chromatography, as recognition components of chiral stationary phases, and by capillary electrophoresis (CE) as soluble chiral selec-tors. Four chiral stationary phases for chromatography with the selectors vancomycin, ristocetin, teicoplanin, and the teicoplanin aglycone are commercialized under the trade name Chirobiotic by Astec and Supelco. Various aspects of analytical applications of glycopeptide antibiotics have been extensively covered in the recent reviews cited above. As an example. Table 2 shows some representative results for CE enantioseparations with vancomycin, ristocetin A, and teicoplanin, which were taken from Ref. 39. 

Further analytical applications of glycopeptide antibiotics involve the development of enantioselective poten-tiometric membrane electrodes employed as sensors for chiral drugs. A carbon paste electrode impregnated with vancomycin or teicoplanin was used for detection of 5-flurbiprofen or / -baclofen (Figure 7) with high sensitivity and selectivity." " ... 

In 2001, the same group reported the application of this key methodology in the synthesis of the aglycon of teicoplanin, which, like vancomycin, is an antibiotic, used for the treatment of methicillin-resistant Staphylococcus aureus (Scheme 2.27) [127]. This was a very successful demonstration of the versatility, mildness, and functiontJ group tolerance of this arylation reaction. 

In recent years, the application of macrocyclic glycopeptide CSPs has been expanded to SFC, and teicoplanin aglycone phase (Chirobiotic TAG) was found to be the most effective closely followed by teicoplanin CSP (Chirobiotic T) [144, 184]. Because of a large number of polar groups available on the Chirobiotic CSPs, it is often required to work with considerable amount of polar additives in the mobile... 

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