Supramolecular Host-Guest Asymmetric Induction In Organic Synthesis

Reprint Address: Santos, LS (reprint author), Talca Univ, Lab Asymmetr Synth, Chem Inst Nat Resources, POB 747, Talca, Chile.In past decades, the pharmacopoeia was dominated by racemates, but since the emergence of new technologies in the 1990s that allowed the preparation of pure enantiomers in significant quantities, the awareness and interest in the stereochemistry of drug actions have increased. In this short review, the implementation of several hosts, guests, building blocks and methods in host-guest supramolecular chemistry was outlined with an emphasis on the synthetic aspects, catalyst libraries and molecular recognition. Solid-state host-guest interactions, intra- and intermolecular host-guest photoreactions in solution and in the solid state, molecular and supramolecular self-assembly and molecular recognition between host and guests, and some specific and important reactions, such as aldol and Michael reactions, were reviewed

Stereoselective bioreduction of beta-carboline imines through cell-free extracts from earthworms (Eisenia foetida)

Mirabal-Gallardo, Y (Mirabal-Gallardo, Yaneris); Soriano, MDC (Soriano, Maria del Pilar C.) ; Santos, LS (Santos, Leonardo S.). Univ. Talca, Lab Asymmetr Synth, Chem Inst Nat Resources, POB 747, Talca, Chile.Although remarkable advances have been made over the last decade in organic synthesis, catalysis, and biotechnology, there is still a need to introduce and develop new processes for chemical production to achieve sustainable and cleaner approaches to support the increasing global pharmaceutical/chemical industry. There is a growing need to produce optically active compounds in high yields to maintain and support areas such as pharmaceutical and natural product synthesis. Thus, chemists today are looking for alternative reactions carried out under green conditions. In this context, we describe beta-carboline imine reductions employing cell-free extracts from red Californian earthworms (Eisenia foetida) in high yields and enantiomeric excesses. The enantiomeric excess values of the bioreduction showed no dependence on the imine 1a-g substituents to afford amines with an (R)-configuration. Based on these data, a model for the cell-free extract from the earthworm is proposed. (C) 2013 Elsevier Ltd. All rights reserved

Short Total Synthesis of (-)-Lupinine and (-)-Epiquinamide by Double Mitsunobu Reaction

Santos, LS (Silva Santos, Leonardo. Univ Talca, Chem Inst Nat Resources, Lab Asymmetr Synth, Talca, ChileAlternative total syntheses of (-)-lupinine (1) and (-)-epiquinamide (2) have been described via the key intermediate 3 obtained from the addition of 2-trialkylsilyloxyfuran 5 to N-acyliminium intermediate derived from 4. The major R, R-isomer 8 obtained from the Mannich reaction was converted into its R, S-isomer through Mitsunobu reaction. Then, a second Mitsunobu reaction of 3 led to cyano 9 and azido 11 derivatives, which were converted into 1 and 2 in 33 and 36% overall yield from 4, respectively. The synthetic route is amenable for the generation of several quinolizidine alkaloids

Enantioselective total synthesis of (S)-(+)-lennoxamine through asymmetric hydrogenation mediated by L-proline-tetrazole ruthenium catalyst

Santos, LS (reprint author), Univ Talca, Chem Inst Nat Resources, Lab Asymmetr Synth, POB 747, Talca, ChileA novel asymmetric synthetic strategy to prepare isoindolobenzazepine based lennoxamine alkaloid has been achieved in high ee% starting from 2-(benzo[d][1,3]dioxol-5-yl)ethanamine and 1-(chloromethyl)-2,3-dimethoxybenzene in 5 steps and with a 34% overall yield. The potentiality of this route involved the Bischler-Napieralsky cyclization that leads to tetracyclic indolinium skeleton, generation of chiral center through asymmetric hydrogen-transfer reaction employing L-proline-tetrazole as chiral ligand with Ru/Ir/Rh, and anodic oxidation as the key steps in the synthesis. (C) 2012 Elsevier Ltd. All rights reserved

Synthesis of the Indolo[2,3-a]quinolizidine Ring through the Addition of 2-Siloxyfurans to Imines and Intrinsic Reaction Coordinate Calculations

Santos, LS (reprint author), Talca Univ, Chem Inst Nat Resources, Lab Asymmetr Synth, POB 747, Talca, ChileA concise asymmetric diastereoselective strategy for the synthesis of indolo[2,3-a]quinolizidine derivative 1 was developed using diastereoselective addition of 2-siloxyfurans 4 to imine 3 through chiral auxiliary induction. The addition of an ionic liquid as additive in the reaction favored the anti configuration in the major adduct. The stereochemical outcome of the antilsyn (threolerythro) selectivity was rationalized based on transition state and IRC calculations at DFT (B3LYP) and MP2 theories. MP2 calculations was shown to be the method of choice in these systems, which orbital desymmetrizations were observed in the anti transition state of the addition of 4 to 3 and secondary orbital interactions allowed us to rationalize the production of the major anti-adduct 6. Furthermore, the work also suggested that 2-(triisopropylsiloxy)furan (4a) was the nucleophile of choice in this kind of Mannich reaction. Moreover, the strategy features the use of the Mitsunobu reaction to insert an amino group with the correct configuration into amine 2, key intermediate to achieve 1. The synthetic route can also be applied in the total synthesis of promising aza-beta-carboline compounds