Tetracyclines. 9. Total synthesis of dl-terramycin

Abstract

100, 3290 (1978), footnote 44) and °,( +) = 365.7 kcal mol-1 can be used to obtain PA(/-C4Hs) = 198.0 kcal mol-1. This value, combined with PA(NH3) -PA(/-C4H8) = 8.6 kcal mol-1 (ref 2), yields PA(NH3) = 206.6 kcal mol 1. This is higher than the value of PA(NH3) = 202.3 kcal mol 1 which was used in ref 3 and throughout the present paper. Using the more recent reference value, all proton affinities will be higher, and all ion heats of formation will be lower by 4.3 kcal mol-1 than the values quoted in the paper. Note, however, that all the discussion in this work is based on relative proton affinities of amines and amino acids, and the conclusions are qualitatively and quantitatively unaffected by the absolute PA values.

Natural Products as Platforms To Overcome Antibiotic Resistance

“…Muxfeldt’s synthesis of the considerably more complex terramycin ( 129 ) avoids a number of synthetic pitfalls, namely various degradation pathways by retro-aldol-type mechanisms. 144 While certainly an innovative work, their synthetic efforts are still not of significant use to the drug discovery field, given their 22-step sequence yielding only 0.06% of racemic terramycin. A more viable synthetic route to a tetracycline was not known until Stork’s 1996 synthesis of a 12a-deoxygenated tetracycline ( 136 ), which would require only C12 oxidation to yield the core structure, starting from juglone and requiring only 16 steps.…”

Fortschritte in der Chemie und Biologie natürlicher Antibiotika

“…Es überrascht daher nicht, dass der hohe Grad molekularer Komplexität in einem trügerisch einfach erscheinenden Kohlenstoffgerüst angesichts der wichtigen antibakteriellen Breitbandwirkung der Tetracycline die Aufmerksamkeit vieler Synthesechemiker auf sich gelenkt hat. Wegweisende Arbeiten mit Blick auf die Totalsynthese von Tetracyclinen wurden unter anderem in den Laboratorien von R. B. Woodward, [23] H. Muxfeldt [24] und G. Stork durchgeführt. [25] Ebenso ist eine Semisynthese von Tetracyclinen durch H. H. Wasserman et al von Bedeutung.…”

Syntheses of linear tetracyclic antibiotics—tetracyclines and anthracyclines

“…After methylation of (26) with diazomethane, the product was converted into the ketal (27) yield, by the usual method. This derivative was transformed into the dihydroanthraquinone (28) in 85% yield, using dithionite in sodium hydroxide, and then subjected to cyclization by treatment with calcium oxide and zinc in glycerol-water at 14OOC to produce 8.4% of the naphthacenetrione (29).…”