Terramycin synthesis

For almost half a century, tetracycline (68) has been well-known as a major antibiotic from the viewpoint of its unique structural features as well as antibacterial activities 24). The total synthesis of tetracycline families was initiated by Woodward s 6-demethyl-6-deoxytetracycline synthesis in 1962 (25), followed by Muxfeldt s terramycin synthesis in 1968 (26), and culminated by Stork s 12a-deoxytetracycline synthesis in 1996 (27). However, all these syntheses have been accomplished only in racemic forms. The total synthesis of... 

Other key classes of antibacterials include the tetracyclines (Aureomycin, Terramycin), macrolides (erythromycin, Zithromax, Biaxin), and aminoglycosides (streptomycin, amikacin, neomycin). These antibacterials are protein synthesis inhibitors. 

Among the recent outstanding contributions to the chemistry of natural products is the conformational analysis designed by Derek Barton. He used it for the structural determinations of many complex molecules such as P-amyrin and cycloartenol. Robert B. Woodward was involved in the structural determinations of penicillin, strychnine, patalin, terramycin, aureomycin and the synthesis ofVitamin B12. 

Acidic hydrolysis of MOM ethers is not easy 3% concentrated HQ in aqueous EtOH and trifluoroacetic acid in dichloromethane at room temperature are typical conditions taken from the solo synthesis of Pleuromutilin by Gibbons [Scheme 4.238J.444 At the other extreme are the remarkably easy scission of a phenolic MOM group activated by an adjacent carbonyl in Muxfeldfs synthesis of Terramycin [Scheme 4.239J44-15 and the use of an acidic exchange resin in re-fluxing methanol to cleave a MOM ether and a dioxolane used in a synthesis of 7-deoxypancratistatin [Scheme 4.240].446... 

The last step in the first total synthesis of the tetracycline antibiotic terramycin (1) by Muxfeldt and co-workers5 involved dialkylation of a primary amine group at C4. 

Startg. aldehyde allowed to react with 2-phenyl-2-thiazolin-5-one in tetrahydro-furan in the presence of basic lead acetate product. Y 11%. - This is a stage in a total synthesis of dl-Terramycin, a tetracycline derivative. H. Muxfeldt et al.. Am. Soc. 90, 6534 (1968). 

Other kinds of antibiotics attack bacteria in different ways from the penicillins and cephalosporins. Many interfere with the synthesis or functioning of bacterial DNA. The tetracyclines (e.g., Achromycin and Terramycin) and erythromycin, for example, inhibit bacterial protein synthesis, and rifampin (important in treating tuberculosis) inhibits RNA synthesis from DNA. 

The successful total synthesis of the major antibiotic terramycin constitutes a versatile two-stage process which augments previous approaches and may afford novel members of this therapeutic class. 

An account of the total synthesis of dl-Terramycin, a highly substituted and labile tetracyline derivative, has been published A mixture of NaNHg and Na-tert-butoxide prepared from NaNHg and Zert-butanol is a highly reactive base. Reductions including reductive substitutions of a,/5-unsaturated to saturated acids as well as autoxidations of hydrocarbons have been performed with Li in hexamethylphosphoramide. Phosphatoplumbic acids have been used as efficient oxidants in methanolic and aqueous medium... 

---