Anthracyclinones. Part 5. Synthesis of some anthracyclinones and 4-hydroxyanthracyclinones containing a tertiary methyl carbinol function in ring A from D-glucose precursors

Abstract

Reaction of 3-C-Methyl-1,2-O-isopropylidene-α-D-ribo-pentodialdo-1,4-furanose (8a) with leuco-quinizarin (2,3,4a,9a-tetrahydroanthracene-1,4,9,10-tetraone)(1a) in alkaline solution followed by aerial oxidation gave mainly (5S)-3-C-methyl 1,2-O-isopropylidene-5-(quinizarin-2-yl)-α-D-ribofur-anose (9a), acid hydrolysis of which gave the quinizarinylpyranose (14a). Similarly 3-O-benzyl-3-C-methyl-1,2-O-isopropylidene-α-D-ribopentodialdo-1,4-furanose (8b) and leucoquinizarin gave the (5S)-1,4-furanose derivative (9c) from which the (5S)-O-benzyl quinizarinyi pyranose (14b) was obtained. In contrast, the O-benzylfuranose (8b) with leucoquinizarin and DBU gave a mixture of (5R) and (5S)3-O-benzyl-3-C-methyl-1,2-O-isopropylidene-5-(quinizarin-2-yl)-α-D-ribofuranose (9d) and (9c) respectively. The (5R)-derivative produced the (5R) quinizarinylpyranose (15a) from which the corresponding (10R)-anthracyclinone (19c) was obtained. Similarly the (10S)-anthracyclinones (19a) and (19b) respectively were prepared from (9a) and (9c) respectively, and the latter was debenzylated with boron trichloride to produce (19a). In a similar manner the O-benzyl aldehyde sugar (8b) with 5-hydroxyleucoquinizarin (1b) in DMF with DBN gave after aerial oxidation the (5R), (5S) and related 5-deoxy hydroxyglycitylanthraquinones (9e), (9f), and (9g) respectively. Each of these was converted into the corresponding (10R), (10S), and (10R) 7-deoxy-4-hydroxyanthracyclinones (19i), (19j), and (19h) by the same general series of reactions outlined above. Structures of the compounds were confirmed by UV, mass, IR, CD, and ¹H NMR spectroscopy.