Stereoselective Synthesis of 4-Deoxyanisomycine Homologues and Related 2-Phenethyl-3-hydroxy-pyrrolidines

There is considerable interest in the synthesis of optically active cyclic amino alcohols since many representatives have been reported to exhibit diverse, strong physiological effects. One of these classes of compounds are 2-alkyl- and 2-aryl- 3-hydroxypyrrolidines. Representative examples are the antibiotic preussin the hypertensive alkaloid codonopsine and the antibiotic anisomycin. Here we would like to present an effective synthesis of 2-(2-aryletyl)-3-hydroxypyrrolidines and their derivatives based on our non-classical Wittig reaction of the 5-aryl substituted 2-aminobutane-4-lactones yielding enantiomerically pure substituted 3a,4-dihydro-2H-furo[3,2-b]pyrrol-5(3H)-ones. (Synlett 2011, 1631-1637.) Subsequent reductive treatment of such bicyclic tetramic acid analogues has opened the door towards methylene homologues of 4-deoxyanisomycins or extrapolated l-phenylalanylamides – methylene homologues of substances with potential anti-HIV activity. (J. Chem. Soc. - Perkin Trans. 1 2001, 1421-1430.)