Glycopeptide antibiotics vancomycin

A47934 - peptide antibiotic (glycopeptide antibiotics, vancomycin and chioroeremomycin, also contain this amino acid)... 

The use of macrocyclic antibiotics as chiral selectors for HPLC was first proposed by Armstrong et al. [50] in 1994. The most successful of the CSPs are based on the glycopeptide antibiotics vancomycin, teicoplanin and ristocetin A and are commercially available through Advanced Separation Technologies Inc. (Astec Inc.) as Chirobiotic V , Chirobiotic 1 and Chirobiotic R , respectively. More recently, a number of other derivatives of these antibiotics have also been developed offering different stereoselectivities. A comprehensive handbook is now available from Astec Inc. [51 ] alongside a number of recent review articles... 

Two EPMEs based on macrocyclic glycopeptide antibiotics—vancomycin and teicoplanin—were designed for the assay of acetyl-L-carnitine [44]. The linear concentration ranges for the proposed electrodes were 10 5-10-2 mol/L for the vancomycin-based electrode and 10 4-10-2 mol/L for the teicoplanin-based electrode, with slopes of 58.1 and 55.0mV/p(acetyl-L-camitine), respectively. The enantioselectivity was determined over D-carnitine. 

Three EPMEs based on macrocyclic glycopeptide antibiotics— vancomycin and teicoplanin (modified or not with acetonitrile)—were proposed for the determination of l- and D-enantiomers of methotrexate (Mtx) [48]. The linear concentration ranges for the proposed enantioselective membrane electrodes were between 10 6 and 10-3 mol/L for l- and D-Mtx. The slopes of the electrodes were 58.00 mV/pL-Mtx for vancomycin-based electrode, 57.60 mV/pD-Mtx for teicoplanin-based electrode and 55.40 mV/pD-Mtx for teicoplanin modified with acetonitrile-based electrode. The detection limits of the proposed electrodes were of 10 8 mol/L magnitude order. All proposed electrodes proved to be successful for the determination of the enantiopurity of Mtx as raw material and of its pharmaceutical formulations (tablets and injections). 

Figure 1.3 Chemical structures of glycopeptides antibiotics vancomycin (1) [1], eremomycin (2) [15a], ristocetin A (3) [15b], and teicoplanin (4) [15c],...

Davis and Fanelli applied the sulfinimine mediated asymmetric Strecker synthesis to the enantioselective synthesis of the racemization-prone (/ )-(4-methoxy-3,5-dihydroxyphenyl)glycine (134) from 133.81 This amino acid is the central amino acid of the clinically important glycopeptide antibiotic vancomycin as well as related antibiotics. 

Evans et al. [161] applied this strategy to the synthetic approach to the glycopeptide antibiotic vancomycin and modified the reduction step by using CrCl2 instead of Zn/AcOH. In the synthetic studies on vancomycin by Yamamura and coworkers [162] even no reduction step was necessary. This macrocyclization method has also been used in the synthesis of OF4949-III and K-13 [163]. 

Figure 17 Structure of the glycopeptide antibiotic vancomycin bound to the cell wall terminus D-Ala-D-Ala. Substitution of D-Ala-D-Ala for D-Ala-D-lactate eliminates an essential FI bond resulting in resistance.

The group of Bakhtiar [57-59] described the chiral bioanalysis of MPH in various matrices, utilizing a number of sample pretreatment strategies, separation on a Chirobiotic V columns, and the use of positive-ion APCI-MS in SRM mode. The chiral selectivity of the Chirobiotic V column is based on the use of the macrocyclic glycopeptide antibiotic vancomycin. The column can be used in both aqueous and organic mobile phase. 

Figure 2.14 Mutasynthesis of glycopeptide antibiotics vancomycin, 3,5-dihydroxyphenyl-glycine (DPG), and vancomycin-type antibiotics.

Based on these experiences with a variety of catalyst-dependent, site-selective reactions, we chose to investigate site-selective functionalization of the glycopeptide antibiotics vancomycin (74) and the teicoplanins (75, the congener). These decisions were made for primarily chemical reasons - we were inspired by the high level of chemical complexity exhibited by these molecules. However, we also wished to create the opportunity to contribute new, potentially improved analogs of these so-called antibiotics of last resort to the field of infectious disease therapy [122-125]. The pursuit of analogs of these storied antibiotics is... 

FIGURE 4.19 The glycopeptide antibiotic vancomycin and lipoglycopeptide antibiotic teicoplanin. 

---