Alkaloids Isolation and Asymmetric Synthesis

Lycopodium Alkaloids Isolation and Asymmetric Synthesis Ac, 0 1)K0H, MeOH H... 

Lycopodium alkaloids Isolation and asymmetric synthesis 12TCC(309)1. One-pot asymmetric 6TC-azaelectrocyclization as a new strategy for alkaloid synthesis 13H(87)729. 

In the arena of (3-lactone synthesis, recent advances such as the use of NHC, phosphine, or isothiourea catalysts have expanded the founding work employing alkaloids for the asymmetric synthesis of these targets. Methodologies have incorporated both in situ generated monosubstituted and isolable disubstituted ketenes as well as recent studies from Romo accessing ammonium enolates by means of an in situ carboxylic acid activation strategy. These protocols allow access to (3-lactones, with the full complement of substitution, in routinely exquisite levels of diastereo- and enantioselectivity. 

Another microwave-mediated intramolecular SN2 reaction forms one of the key steps in a recent catalytic asymmetric synthesis of the cinchona alkaloid quinine by Jacobsen and coworkers [209]. The strategy to construct the crucial quinudidine core of the natural product relies on an intramolecular SN2 reaction/epoxide ringopening (Scheme 6.103). After removal of the benzyl carbamate (Cbz) protecting group with diethylaluminum chloride/thioanisole, microwave heating of the acetonitrile solution at 200 °C for 2 min provided a 68% isolated yield of the natural product as the final transformation in a 16-step total synthesis. 

Synthesis of Optically Active Epoxides. Alkaloids and alkaloid salts have been successfully used as catalysts for the asymmetric synthesis of epoxides. The use of chiral catalysts such as quinine or quinium benzylchloride (QUIBEC) have allowed access to optically active epoxides through a variety of reaction conditions, including oxidation using Hydrogen Peroxide (eq 5), Darzens condensations (eq 6), epoxidation of ketones by Sodium Hypochlorite (eq 7), halohydrin ring closure (eq 8), and cyanide addition to a-halo ketones (eq 9). Although the relative stereochemistry of most of the products has not been determined, enan-tiomerically enriched materials have been isolated. A more recent example has been published in which optically active 2,3-epoxycyclohexanone has been synthesized by oxidation with t-Butyl Hydroperoxide in the presence of QUIBEC and the absolute stereochemistry of the product established (eq 10). ... 

Because benzylisoquinolines have been available synthetically (in racemic form) for decades, there is quite a bit of chemistry known regarding their use as key intermediates in the synthesis of a number of more complex isoquinoline alkaloids. The asymmetric synthesis of benzylisoquinolines has been used to complete total synthesis of representative members of several of these alkaloid classes. As shown in Figure 6, the protoberberine alkaloid norcoralydine, the aporphine alkaloid ocoteine, the isopavine alkaloid reframoline and the morphinan 0-methylflavinantine have been made available in optically active form for the first time (except by isolation or resolution) using this approach. 

During the last decade, new alkaloids of this type have been isolated, methods of asymmetric synthesis have been developed, the absolute stereochemistry of a number of alkaloids has been established, and the mechanisms of certain rearrangement reactions of furo- and pyrano-quinoline alkaloids of the group have been studied. Additional pyrano-quinolines of the flindersine type have been discovered, and new methods of synthesis have been developed. Isopropyldihydrofuroquinoline alkaloids without a hydroxy group in the side chain are characteristic components of Lunasia species, but not much new work on this group has appeared recently. 

Synthetic work on the mesembrane group will no doubt be further stimulated by reports on their central nervous system activity and somewhat surprising biosynthesis. An interesting asymmetric synthesis of unnatural (+ )-mesembrine (38) has been announced (Scheme 4). The key intermediate (35), prepared in nine steps from 1,2-dimethoxybenzene, was treated with L-proline pyrrolidide (36) under conditions typical for the preparation of enamines. The product was not isolated but subjected to reaction with methyl vinyl ketone followed by acid treatment to give the cyclohexenone (37) in 38 % overall yield. The last step in the synthesis [(37) — (38)] was based on previous synthetic work on mesembrine alkaloids. The synthetic (+ )-mesembrine (38) was shown to exhibit a positive Cotton effect and thus an antipodal relationship to natural (— )-mesembrine. The mesembrine analogues (40 = H or OMe, = H, Me, or CHjPh) have... 

Osuna, M. R, Aguirre, G., Somanathan, R, Molins, E. Asymmetric synthesis of amathamides A and B novel alkaloids isolated from Amathia wilsoni. Tetrahedron Asymmetry 2992, 13,2261-2266. 

A review was written about the formation of 2-substituted pyridines from pyridine N-oxides (13ARK154) and another review touches on the difficulty of identifying the various 3-alkyl pyridinium and 3-alkyl tetrahy-dropyridine alkaloids that can be isolated firom an artic sponge, Haliclona tnscosa (13PR391). Other reviews focus on the utility of pyridine-based compounds in synthesis for example, the use of optically active pyridine ligands for asymmetric synthesis (13CCR1887). 

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