Asymmetric total synthesis of(–)-protoemetinol,(–)-protoemetine,(–)-emetine, and (–)-tubulosine by highly stereocontrolled radical cyclisations
01 Jan 1990-Journal of The Chemical Society-perkin Transactions 1 (The Royal Society of Chemistry)-Iss: 5, pp 1469-1476
TL;DR: Both enantiomers of the menthyl halfesters (10) and (23) of ethylmalonic acid were converted into (+)-(4S,5R)-4-(2-benzyloxyethyl)-5-ethyl-3,4,5,6-tetrahydro-2-pyrone (18) as discussed by the authors.
Abstract: Both enantiomers of the menthyl half-esters (10) and (23) of ethylmalonic acid were converted into(+)-(4S,5R)-4-(2-benzyloxyethyl)-5-ethyl-3,4,5,6-tetrahydro-2-pyrone (18). A mixture of the trans-(18) and cis-lactones (19) in a ratio of ca. 4 : 1 was prepared by way of radical cyclisation of the (E)-α,β-unsaturated esters (16), while the former (18) was synthesised with high stereoselection by the cyclisation of the (Z)-esters (26). The lactone (18) was enantioselectively transformed into (–)-protoemetimol (5) and (–)-protoemetine (4), correlated to (–)-emetine (1) and (–)-tubulosine (3).
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TL;DR: A catalytic asymmetric allylation of 3,4-dihydroisoquinoline was carried out with allyltrimethoxylsilane-Cu as the nucleophile and the allyl adduct obtained was applied to the synthesis of several isoquinoline alkaloids such as crispine A and homolaudanosine.
Abstract: A catalytic asymmetric allylation of 3,4-dihydroisoquinoline was carried out with allyltrimethoxylsilane-Cu as the nucleophile in the presence of DTBM-SEGPHOS as the chiral ligand to afford corresponding chiral 1-allyltetrahydroisoquinoline derivatives in good yield and stereoselectivity. The allyl adduct thus obtained was applied to the synthesis of several isoquinoline alkaloids such as crispine A and homolaudanosine. The reaction was further used for the synthesis of the isoquinoline moiety of schulzeine A.
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TL;DR: The potential of this strategy is demonstrated in the synthesis of biologically interesting natural product analogues not accessible through synthetic elaboration of alkaloid precursors available from nature, for example, thieno[3,2-a]quinolizidine derivatives.
Abstract: Here we present a general and common catalytic asymmetric strategy for the total and formal synthesis of a broad number of optically active natural products from the corynantheine and ipecac alkaloid families, for example, indolo[2,3-a]- and benzo[a]quinolizidines. Construction of the core alkaloid skeletons with the correct absolute and relative stereochemistry relies on an enantioselective and diastereodivergent one-pot cascade sequence followed by an additional diastereodivergent reaction step. This allows for enantio- and diastereoselective synthesis of three out of four possible epimers of the quinolizidine alkaloids that begin from common and easily accessible starting materials by using a common synthetic route. Focus has been made on excluding protecting groups and limiting isolation and purification of synthetic intermediates. This methodology is applied in the total synthesis of the natural products (-)-dihydrocorynantheol, (-)-hirsutinol, (-)-corynantheol, (-)-protometinol, (-)-dihydrocorynantheal, (-)-corynantheal, (-)-protoemetine, (-)-(15S)-hydroxydihydrocorynantheol, and an array of their nonnatural epimers. The potential of this strategy is also demonstrated in the synthesis of biologically interesting natural product analogues not accessible through synthetic elaboration of alkaloid precursors available from nature, for example, thieno[3,2-a]quinolizidine derivatives. We also report the formal synthesis of (+)-dihydrocorynantheine, (-)-emetine, (-)-cephaeline, (-)-tubulosine, and (-)-deoxytubulosine.
54 citations
TL;DR: In this article, a review summarises electrochemical reductive intramolecular cyclisations, including transition-metal catalysed reactions, and presents some selected examples of organic halide electroreductions with further intramerolecular coupling reactions, carbonyl group reductions with further coupling, and intramerial cyclisations involving electrogenerated bases.
Abstract: This review summarises electrochemical reductive intramolecular cyclisations, including transition-metal catalysed reactions. It presents some selected examples of organic halide electroreductions with further intramolecular coupling reactions, carbonyl group reductions with further coupling and intramolecular cyclisations involving electrogenerated bases.
37 citations
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TL;DR: In this article, new phosphonoester reagents and reaction conditions are described which yield Z-alpha, beta-unsaturated esters stereoselectively and in high yield from aliphatic and aromatic aldehydes.
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TL;DR: In this article, a theoretical study of the relative rates and the regio-and stereo-chemistry of ring closure of a variety of alkenyl radicals was performed using MM2 force-field calculations.
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