Nogalamycin synthesis

In addition to electrophilic functionalization, the 5,6-double bond of the adducts (see (222)) is reported to undergo high-pressure [4 + 2]-cycloaddition with jV-(2,4-dinitrophenyl)isoquinolinium chloride (223) (Bradsher cycloaddition) to afford the naphthol-substituted isoxazoline (224) (Equation (61)), which was used for the total synthesis of nogalamycin analogues <92JOC644>. 

Allyl bromide, methyl iodide and benzyl bromide are the triumvirate of common alkyl halides that alkylate metal alkoxides readily. In the case of phenols, potassium carbonate [Scheme 4.230]438 or cesium carbonate are competent bases whereas primary and secondary alcohols require potassium hydroxide [Scheme 4.231J,402 but the strongly basic conditions limit the scope of the method. For example, attempts to alkylate the secondary and phenolic hydroxyl groups of the intermediate 232.1 in a synthesis of the antibiotic Nogalamycin using the traditional metal alkoxide alkylation failed owing to competing sec-... 

Wiley PF. Nogalamycin chemistry and analog synthesis. El Khadem HS. ed. Anthracydine Antibiotics. New York Academic Press, 1982 97-117. 

Full details of the synthesis of nogalamycin cogeners have been... 

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