Tetracyclines. V.¹ A Total Synthesis of (±)-6-Deoxy-6-demethyltetracycline

Chemical Modification of the Tetracyclines

“…The totally synthetic route of W oodward and the Pfizer Company is much more circuitous than the totally synthetic pathway of Muxfeldt and coworkers and gives considerably inferior yields (CONOVER et al 1962;KORST et al 1968;MUXFELDT and ROGALSKI 1965;MUXFELDT et al 1979). It is only logical, therefore, that attempts at finding new tetracyclines not producible by semisyn- w. ROGALSKI thetic means have generally followed the synthetic pathway of Muxfeldt, which is distinguished by a particularly elegant structuring of rings A and B.…”

“…While Hoechst proceeds from the aldehyde (214) and describes the tetracyclic mixture (215), the E. Merck research group se1ected the aldehyde (218) (BOOTHE et al 1959;MUXFELDT and ROGALSKI 1965) to produce the tetracyclic ring system (Fig.28) …”

Synthesis of Tetracycline Ring A Analogs

“…Therefore, another approach was tried involving conversion of the basic amino moiety to a neutral species, followed by cyclization and subsequent removal of the protective group. The benzoylamino group was chosen since conditions for its hydrolysis have been well documented (10)(11)(12). The amino ketal ester (XIV) was converted to the benzoylamino derivative (XVIII) by treatment with benzoyl chloride.…”

Naturstoffsynthese im Wandel der Zeit

“…[18] Sie verlief bis zur Zwischenstufe 5 ganz in klassischen Bahnen. [18] Sie verlief bis zur Zwischenstufe 5 ganz in klassischen Bahnen.…”