Designing and testing biomimetic switches: Multireference perturbation theory is used to model a light-driven molecular switch featuring the same photoisomerization mechanism as the chromophore of the visual pigment rhodopsin (see picture; QM/MM: quantum mechanics/molecular mechanics). By exploiting a synthetic route based on nitrilium-cation cyclization, it was shown that the designed system can indeed be prepared and characterized

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The original and classical Mannich-type construct for the tropane skeleton, developed over half a century ago by Willstätter, Robinson and Schöpf as the first biomimetic synthesis, has been employed for the enantioselective construction of 6b-hydroxytropinone. The component compounds of this novel one-step Mannichtype condensation sequence are acetonedicarboxylic acid, methylamine hydrochloride and (2R)-hydroxy-1,4-butanedial, in turn prepared from tert-butyl (R)-3-hydroxy-4-pentenoate as the starting chiral synthon.Tropane alkaloids constitute a group of some 200 natural products, mostly occurring in plants of Solanaceae family, featuring the 8-azabicyclo[3.2.1]octane skeleton as the key structural element. The remarkable biological activity associated to many tropane alkaloids has attracted much attention, achieving a significant folklore and influence in medicine for hundred of years, while their structure elucidation and synthesis has contributed in no small part to the development of organic chemistry since the middle of the 19 th century. [1][2][3][4] A prodigious number of tropane analogues have been synthesized, major efforts being expended in the search for cocaine antagonists or partial agonists. Beside the original and still widely used Mannich-type 5-8 construct for the tropane skeleton a number of synthetic methodologies have since been developed. 9-11 However, few asymmetric versions of cycloadditions for the stereospecific synthesis of tropane analogues are known and still suffer from low yield and poor stereoselectivity. Therefore, most of the non-racemic tropane derivatives were synthesized by the derivatization of natural cocaine or through enantioselective deprotonation of tropinone, 12-14 while others were obtained by resolution or separation of racemic or diastereomeric reaction mixtures. 15Despite a pertinent accumulation of tropane chemistry, no enantioselective variant of the Mannich-type condensation between acetonedicarboxylic acid and methylamine hydrochloride using optically active 2-hydroxysuccinaldehyde or its equivalents as a chiral control element has been described in the literature. It seems likely that concerns about the preservation of the integrity of the stereocenter of the a-hydroxyaldehyde during the reaction, coupled with the commercial availability of 2,5-dimethoxy-2,5-dihydrofuran (a convenient precursor of racemic 2-hydroxysuccinaldehyde), have made the preparation of racemic tropane derivatives through the Mannich-type condensation followed by resolution more attractive. [16][17][18][19][20][21][22][23] Interestingly, the enzymatic resolution of tropinone derivatives, including racemic 6-hydroxytropinone, has been successfully achieved but the absolute configuration of the chiral derivatives could not be determined. 24 In this paper, we describe a direct, enantioselective approach to 6-hydroxytropinone through a suitable adaptation of the classical Robinson-Willstätter route employing an optically active 2-hydroxysuccinaldehyde derivative in the classical one-pot, mult...