Synthesis of antibiotics

H. A. Kirst, in G. Lukacs and M. Ohno, eds., Kecent Progress in the Chemical Synthesis of Antibiotics, Springer-Vedag, Heidelberg, Germany, 1990, p. 39. 

The Stille coupling of an aryl triflate normally calls for the addition of at least one equivalent of LiCl. Presumably, the transmetallation is facilitated by replacing triflate with CP at the palladium intermediate generated from oxidative addition. As Stille demonstrated in 1988, 4-quinolinyl triflate 100 was coupled with phenylstannane 101 in the presence of Pd(Ph3P)4 and LiCl in refluxing 1,4-dioxane to furnish biaryl 102, which was used as an intermediate for the first total synthesis of antibiotic amphimedine (88JA4051). 

If a carbohydrate already contains a nitro group, the nitro-bearing carbon atom can become the nucleophilic center for the coupling of two monosaccharide units (see Section 3.2.2). Suami and coworkers have used this method for the synthesis of antibiotics bearing sugars.102 Atypical example is presented in Eq. 3.63.102b... 

Suzuki, K. Matsumoto, T. In Recent Progress in the Chemical Synthesis of Antibiotics and Related Microbial... 

Addition of (4-methoxybenzyl)magnesium chloride to the pyrroline derivative (312) is a key step in the stereoselective synthesis of antibiotics (—)-anisomicine... 

INAC reactions have also led to enantioselective syntheses of key intermediates in the synthesis of antibiotic l 3-Methylcarbapenem (724), to optically pure derivatives of tetrahydropyrano[2,3] cyclohexane (725a) to novel terahydro-isoxazolo-fused pyrano 2,3-/ quinolines (725b) and to a novel heterocyclic system, isoxazolo[3,4-d]thieno[2,3-b]pyridine (Scheme 2.229) (221). 

Acyloxybutenolides obtained by / -elimination from ribonolactone (see Section IX.2) have served as appropriate chiral intermediates in several synthesis of antibiotics. Barrett and Sheth (205) reported a seven-step synthesis of racemic terI-butyl-8-0-ter/-butyldimethylsilylnonactate, a monomeric moiety of the antibiotic nonactin, from 157. Also, (4,S,6[Pg.189]

Fernandez-Lafuente,R., RoseU, C.M., Piatkowska, B. and Guisan, J.M., Synthesis of antibiotics (cephaloglycin) catalyzed by penicillin G acylase evaluation and optimization of different synthetic approaches. Enzyme Microb. Technol., 1996, 19, 9-14. 

Herezegh P, Kovacs I, Sztaricskai F (1993) In Lukacs G (ed) Recent progress in the chemical synthesis of antibiotics and related microbial products, vol 2. Springer, Berlin Heidelberg New York, p 751... 

Table 12.6 summarizes results obtained in the synthesis of antibiotics in the presence of undissolved substrates catalyzed by penicillin amidase, and... 

J. Jurczak and A. Golfbiowski, The synthesis of antibiotic amino sugars from a-amino aide hydes, Antibiotics and Antiviral Compounds, Chemical Synthesis and Modification, (K. Krohn, H. Kirst, and H. Maas, eds.), VCH, Weinheim, 1993, p. 343. 

The potential of this sequence was applied in Meyers s total synthesis of antibiotic maytansinoids such as (-)-maysine [345]. 

Ynnernilsu, O. and K. Horilu ToLal SynLhcsis of Polyclhcr Antibiotics in G. Lukaes and M. (time. eds. Recent Progress in the Chemical Synthesis of Antibiotics, Springer Verlag, Berlin, Heidelberg, 1990, pp. 448-466. 

Carbohydrates are used increasingly for the synthesis of antibiotics and their analogues. This subject was discussed by J. G. Moffat and S. Umezawa in London (1978) and by C.-H. Wong in Hamburg (2000). Enzymes came into more extensive use S. David discussed the use of immobilized enzymes in preparative carbohydrate chemistry (Ithaca 1986) and C.-H. Wong further developed this subject in Paris (1992). The mechanism of the action of enzymes was discussed by S. G. Withers in his Whistler Award lecture in Cairns (2002). 

However, the synthesis is inferior to the processes based on phenols and glyoxylic acid. One reason is the large amount of waste salts which are inevitably produced. Reductive dehalogenation has been used for the synthesis of antibiotics... 

One common structural element of natural products exhibiting antibiotic properties is the incorporation of a (3-lactam moiety. This structural unit is somewhat labile. Because ozonation is generally recognized as a mild, clean, and selective method for oxidation of a compound, it can be considered an attractive synthetic transformation during the synthesis of antibiotics and their analogues. 

The second example is the biosynthesis of antibiotics. The ppGpp is a positive effector in the synthesis of antibiotics in Streptomyces. The disruption of the ppGpp synthetase relA gene of Streptomyces coelicolor (Chakraburty and Bibb, 1997) and Streptomyces antibioti-cus (Hoyt and Jones, 1999) gives phenotypes unable to produce antibiotics. The disruptants were unable to accumulate ppGpp to the level sufficient for initiation of morphological differentiation and antibiotics production. 

Only a few cases of the synthesis of antibiotics, such as citromicetin, carried out by amino group replacement, and cephalosporin, arc mentioned in the literature most of the reports are dedicated to the use of the antibiotic molecule as a substrate or amine... 

Both 4,5-dihydrooxazoles 3 and 5,6-dihydro-4f/-l,3-oxazines 2 obtained by halocyclization of imidates are cleaved under neutral Or acidic conditions to give trichloroacetamides or amino alcohols which constitute building blocks for the total synthesis of antibiotics and natural products with biological activity144. 

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