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Concept: Total synthesis


Two syntheses of natural viridic acid, an unusual triply N-methylated peptide with two anthranilate units, are presented. The first one is based on peptide-coupling strategies and affords the optically active natural product in 20% overall yield over six steps. A more economical approach with only four steps leads to the similarly active racemate by utilizing a Ugi four-component reaction (Ugi-4CR) as the key transformation. A small library of viridic acid analogues is readily available to provide first SAR insight. The biological activities of the natural product and its derivatives against the Gram-negative bacterium Aliivibrio fischeri were evaluated.

Concepts: Protein, Amino acid, Molecular biology, Microbiology, Escherichia coli, Total synthesis, Chemical synthesis, Ugi reaction


A synthesis fit for a king: The total synthesis of (±)-kingianins A, D, and F has been achieved in ten steps. Key features include the gram-scale synthesis and partial reduction of a conjugated tetrayne to a (Z,Z,Z,Z)-tetraene, the domino 8π-6π electrocyclic ring closure of a (Z,Z,Z,Z)-tetraene, and the radical-cation-catalyzed formal Diels-Alder dimerization of functionalized bicyclo[4.2.0]octadiene precursors.

Concepts: Total synthesis, Paclitaxel total synthesis, Chemical synthesis, Vector space, Formal language


The total synthesis of the Lycopodium alkaloid lyconadin A was accomplished and it was applied to the total syntheses of the related congeners, lyconadins B, and C. Lyconadin A has attracted attention as a challenging target for total synthesis due to the unprecedented pentacyclic skeleton. Our synthesis of lyconadin A features a facile construction of the highly fused tetracyclic skeleton through a combination of an aza-Prins reaction and an electrocyclic ring opening followed by a formation of a C-N bond. Transformation of the bromoalkene moiety of the tetracycle to a key enone intermediate was extensively investigated, and three methods via sulfide, oxime, or azide intermediates were established. A pyridone ring was constructed from the key enone interme-diate to complete the synthesis of lyconadin A. A dihydropyridone ring could also be formed from the same enone intermediate, leading to a synthesis of lyconadin B. Establishment of the conditions for an electrocyclic ring opening without formation of the C-N bond resulted in completion of the total synthesis of lyconadin C.

Concepts: Chemical reaction, Functional group, Total synthesis, Paclitaxel total synthesis, Chemical synthesis, Rational number, Functional groups, Reserpine


The first total synthesis of the dimeric berberine alkaloid ilicifoline (ilicifoline B) is reported. Its carbon skeleton is constructed from ferulic acid, veratrole, and methanol. The synthesis reported herein employs starting materials solely derived from wood. The natural product is thus constructed entirely from renewable resources. The same strategy is applied to a formal total synthesis of morphinan alkaloids. The use of wood-derived building blocks (xylochemicals) instead of the conventional petrochemicals represents a sustainable alternative to classical synthetic approaches.

Concepts: Oxygen, Alcohol, Total synthesis, Natural resource, Paclitaxel, Alkaloid, Natural products, Natural capital


A formal total synthesis of the spiroketal containing cytotoxic myxobacteria metabolite spirangien A (1) is described. The approach utilizes a late introduction of the C20 alcohol that mirrors the biosynthesis of this compound. The key steps involved a high yielding cross metathesis reaction between enone 6 and alkene 7 to give E-enone 4 and a Mn-catalyzed conjugate reduction α-oxidation reaction to introduce the C20 hydroxyl group. Acid treatment of the α-hydroxyketone 4 gave spiroketal 19 which was converted into known spirangien A (1) advanced intermediate spiroketal 3.

Concepts: Alcohol, Functional group, Total synthesis, Olefin metathesis, Functional groups, Richard R. Schrock, Hydroxyl, Alkane metathesis


An efficient total synthesis of (-)-epothilone B has been achieved in ca. 8% yield over 11 steps from 9 (or 10 steps from 7/8), which features a bissiloxane-tethered ring closing metathesis reaction to approach the trisubstituted (Z) double bond and forms a new basis for further development of an industrial process for epothilone B and ixabepilone.

Concepts: Total synthesis, Paclitaxel total synthesis, Olefin metathesis, Chemical synthesis, Epothilone, Process management, Ixabepilone, Sorangium cellulosum


Three keys to success: A concise method for the construction of a tricyclic substructure (2) of haliclonin A (1) in racemic form is described. This synthesis features a new Pd-mediated chemoselective carbonyl-enone coupling reaction, an organocatalytic reaction, and a ring-closing metathesis reaction for the construction of the macrocyclic ring as key steps.

Concepts: Catalysis, Total synthesis, Olefin metathesis, Key


2-Methoxymethylpyrrolidine best performed, among several other proline derivatives, to control the enantioselective [3+3] annulation of beta-(hetero)aryl-alpha nitro-alpha,beta-enals with commercial 2,2-dimethyl-1,3-dioxan-5-one, a procedure which renders highly-oxygenated nitrocyclohexanes endowed with five new stereocenters. Use of this reaction allowed the development of a total synthesis of the antitumoral natural product (+) pancratistatin; it also converted our previous racemic route to tetrodotoxin into an enantioselective one.

Concepts: Chemical reaction, Total synthesis, Paclitaxel total synthesis, English-language films, Chemical synthesis, Enantiomer, Paclitaxel, Racemic mixture


A very simple and efficient stereoselective approach to cis-2,3-disubstituted piperdines via the reduction of N-acyl iminium ion intermediates is described. Application of this methodology is exemplified by the enantioselective total synthesis of (+)-(2S, 3S)-CP-99,994.

Concepts: Total synthesis, Paclitaxel total synthesis, Chemical synthesis, Ammonium, Iminium


A stereoconvergent access to chiral carbocyclic building blocks is reported. 6-(3'-Hydroxy-4'-methylpent-4'-enyl)-3-methoxy cyclohex-2-enone () that consists of four stereoisomers, i.e., racemic ca. 1 : 1 diastereomers, is converted to enantiomerically pure carbocycles through a combination of regioselective catalytic asymmetric reduction and alkylative remote stereoinduction. The present stereoconvergent strategy has allowed the formal synthesis of bioactive (-)-dysidiolide.

Concepts: Present, Stereochemistry, Hydrogenation, Total synthesis, Chemical synthesis, Enantiomer, Asymmetric induction, Asymmetric synthesis