Stereoselective synthesis of 3-amino-4,5-dihydroxyaldehydes - a novel preparation of N-acetyl-L-daunosamine

A general route for the stereoselective synthesis of 3-amino-4,5-dihydroxya ldehydes, with almost any desired configuration at the three stereogenic ce nters, is described by applying a combination of enzymatic and chemical ste ps. L-Daunosamine 1, for example, the glycosidic fragment of many important anthracycline antibiotics has been prepared by this route starting from O- allyl-L-lactaldehyde (S)-6a. (R)-Hydroxynitrile lyase (HNL) catalyzed addit ion of HCN to (S)-6a yields the 2,3-dihydroxynitrile (2S,3S)-7a with high s tereoselectivity (91% de) in 75% yield. The addition of allyl Grignard to t he O-protected 2,3-dihydroxynitrile (2S,3S)-9a and subsequent hydrogenation of the imino intermediate leads to 4-amino-2,3-dihydroxy-1-heptene (4S,5S, 6S)-12a, which after ozonization and deprotection gives N-acetylated L-daun osamine 14a in a total yield of 15% referring to (S)-6a. The general applic ability of this chemoenzymatic multistep procedure is demonstrated in the s tereoselective synthesis of the unnatural aminodeoxy sugar (2S,3S,4S)-14b, starting from isovaleraldehyde 3. (C) 2000 Elsevier Science Ltd. All rights reserved.