12a-Deoxytetracycline

Although the Pt/02 reaction has been used for oxidation of primary and secondary alcohols [67], hydroxylation of 12a-deoxytetracyclines [68], oxygenation of cholesterol [69], and oxidation of tertiary amines [5f], this... 

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... 

Although the examples shown for the most part use AIBN and tributyltin hydride in refluxing benzene, other solvents can be used. For instance, radical cyclization of 165 in aqueous ethanol using a combination of phosphoric acid and a base led to 166 in 83% yield. In this example, it is clear that heteroatoms can be part of the chain that links the radical precursor and the alkene. Stork introduced a modification that produces protected lactones via radical cyclization. In a synthesis of 12a-deoxytetracycline, Stork converted 167 to 168 under standard conditions, in 90% yield. 0... 

Lactone opening A crucial operation in a synthesis of 12a-deoxytetracycline requires a mild alcoholysis of a lactone under conditions precluding closure of the B-ring, because intermediates with the linear tricarbocyclic array resist further cyclization. After successful lactone opening by treatment with Bu,SnOMe, the a-tetralone unit can be masked as a lactol silyl ether to permit a Dieckmann cyclization to form the A-ring. 

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