Abstract: The synthesis of iminosugars is one of the most active fields in synthetic organic chemistry. Due to the structural resemblance to sugars, these unique molecules have a tremendous potential in biological functions mediated by carbohydrates and have been postulated in the control of diabetes, Gaucher\'s disease, cancer, HIV, and viral infections like influenza. A survey of the literature reveals that the synthesis of 2,3,5-substituted pyrrolidines is not a trivial task specially when the attainment of enantiomerically pure compounds are requested. In this work, we describe the synthesis of enantiomerically pure poly(hydroxymethyl)pyrrolidines (iminosugars) and different routes to selective functionalization of –OH and -NH groups. The optically active pyrrolidine derivatives were obtained from 2-azabicyclo[2.2.1]hept-5-enes, which were synthesized in one step according to the literature procedure by an aza-Diels-Alder reaction between protonated glyoxylate imines possessing two chiral auxiliaries, N-(S)- or N-(R)-1-phenylethyl and (-)-8-phenylmenthyl or (+)-8-phenylneomenthyl, respectively, and cyclopentadiene. These polycyclic aza-Diels-Alder adducts, trough bis-hydroxylation of double bond followed by the oxidative cleavage of the corresponding diols and in situ reduction of the resulting intermediates, afforded 2,3-bis-(hydroxymethyl)-pyrrolidines from which, application of a selective protection/deprotection methodology provided the possibility of regioselective functionalization at positions 1, 2, 3, and 5 of the pyrrolidine scaffold. In conclusion, an efficient and straightforward orthogonal protection/deprotection methodology, allowing selective introduction of functional groups in iminosugars, was developed. References: · Tetrahedron Letters 2006, 47 (43), 7595-7597 · Tetrahedron Letters 1998, 39 (31), 5663-5666 · Tetrahedron 2010, 66 (34), 6797-6805 · Tetrahedron 2011, 67 (37), 7162-7172 · Synthesis 2008, 2008 (EFirst), 971-977 · Tetrahedron Letters 2012, 53 (9), 1029-1032.