ABSTRACT
Background Spiroketals of general structure A (Scheme 1) constitute key structural features of a number of bioactive natural products isolated from insects, microbes, fungi, plants or marine organisms. [1-3] e corresponding aza-spiroketal (cf: general structure B) containing natural products, while less common, are also found in plants, shellsh and microbes.[4,5] For example, pandamarilactone-1 and pandamarine were isolated from the leaves of Pandanus amaryllifolius;[6] solasodine
and its derivatives were isolated from Solanum umbelliferum, which exhibited signicant activity toward DNA repair-decient yeast mutants;[7] azaspiracids are marine phycotoxins isolated from cultivated mussels in Killary harbor, Ireland;[8] and chlorofusin A is a novel fungal metabolite showing the potential as a lead in cancer therapy.[9] In addition, aza-spiropyrans C, being able to equilibrate with the corresponding non-spiro analogue D, is a well known class of compounds possessing photochromic properties for use in the area of photochemical erasable memory,[10] and also found applications as self-development photography, actinometry, displays, lters, lenses of variable optical density,[11] and photomechanical biomaterials etc.[12]
On the other hand, hydroxylated indolizidines [13-20] such as castanospermine, (-)-swainsonine, (+)-lentiginosine [21-23] (1) and (-)-2-epilentiginosine [21-26] (2) constitute a class of azasugars showing potent and selective glycosidase inhibitory activities. [13-20] (1R,8aS)-1-Hydroxyindolizidine 3 has been postulated as a biosynthetic precursor [21-26] of (+)-lentiginosine (1), (-)-2-epilentiginosine (2) and (-)-swainsonine, a potentially useful antimetastasis drug for the treatment of cancer.[15] In addition, these molecules serve as platforms for testing synthetic strategies, and several asymmetric syntheses of both enantiomers of 1-hydroxyindolizidine (3) have been reported. [27-34]In continuation of our
eorts in the development of enantiomeric malimide-based synthetic methodologies, [35-38] we now report concise and highly diastereoselective syntheses of an aza-spiropyran derivative 7 and (1S,8aR)-1-hydroxyindolizidine (ent-3).
