Dedicated to Professor Rolf Huisgen on the occasion of his 85th birthdayThe hydrochlorides of both enantiomers of the antibiotic anisomycin were prepared starting with the −diacetone-fructose×-substituted allene 1 and the N-Boc-protected imine precursor 2a. Addition of an excess of lithiated 1 to 2a provided a 2 : 1 mixture 3a of diastereoisomers, which were cyclized to 4a under base promotion (Scheme 2). The two diastereoisomers of 4a were separated and converted into enantiomerically pure pyrrolidin-3-ones (2R)-5a and (2S)-5a. A similar sequence yielded the N-Tos-protected compounds (2R)-5b and (2S)-5b. Compounds 5a were converted into silyl enol ethers 6 and by subsequent regio-and stereoselective hydroboration into pyrrolidine derivatives 7 (Scheme 3). Straightforward functional-group transformations led to the hydrochlorides 9 of anisomycin (Scheme 3). The (2R) series provided the hydrochloride (2R)-9 of the natural occurring enantiomer, whereas the (2S) series furnished the antipode (2S)-9. The overall sequence to the natural product involved ten steps with eight purified intermediates and afforded an overall yield of 8%. Our stereochemically divergent approach to this type of hydroxylated pyrrolidines is highly flexible and should easily allow preparation of many analogues.Introduction. ± A variety of interesting biologically active natural products contain configurationally defined pyrrolidine substructures among which many bear 3-hydroxy substituents or related functional groups. As a consequence, their synthesis and that of analogues has attracted much attention 1 ). Typical examples of these pyrrolidinol derivatives are ()-preussin, (À)-detoxinine, and (À)-anisomycin (Scheme 1), which display interesting biological activities. We have earlier prepared (À)-preussin and (À)-detoxinine by constructing their pyrrolidine core A from alkoxyallenes B and Nprotected imines C. Lithiation of B at C(1) and addition of these strong nucleophiles to imines C followed by ring closure of the primary adducts provided the required dihydropyrrole derivatives A by an efficient [3 2] cyclization mode [2]. Whereas the stereochemical control of the synthesis of (À)-detoxinine was easily achieved with a chiral side chain R 1 of imine C [3], the preparation of (À)-preussin exploited a chiral auxiliary R 2 at the alkoxyallene building block B. In this synthesis [4], the most-difficult problem was control of the configuration at C(5) of the pyrrolidine. In this report, we demonstrate that a suitable auxiliary also allows the synthesis of both enantiomers of anisomycin.(À)-Anisomycin ± a compound with a 4-methoxyphenyl substituent ± is a secondary metabolite of streptomyces species (Streptomyces grisoleaus and S. roseochromo-
