https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

Multicomponent reactions (MCRs) are fundamentally different from two-component reactions in several aspects. Among the MCRs, those with isocyanides have developed into popular organic-chemical reactions in the pharmaceutical industry for the preparation of compound libraries of low-molecular druglike compounds. With a small set of starting materials, very large libraries can be built up within a short time, which can then be used for research on medicinal substances. Due to the intensive research of the last few years, many new backbone types have become accessible. MCRs are also increasingly being employed in the total synthesis of natural products. MCRs and especially MCRs with isocyanides offer many opportunities to attain new reactions and basic structures. However, this requires that the chemist learns the “language” of MCRs, something that this review wishes to stimulate.

Multicomponent Reactions with Isocyanides.

The direct functionalization of C-H bonds in organic compounds has recently emerged as a powerful and ideal method for the formation of carbon-carbon and carbon-heteroatom bonds. This Review provides an overview of C-H bond functionalization strategies for the rapid synthesis of biologically active compounds such as natural products and pharmaceutical targets.

C-H bond functionalization: emerging synthetic tools for natural products and pharmaceuticals

In studying the evolution of organic chemistry and grasping its essence, one comes quickly to the conclusion that no other type of reaction plays as large a role in shaping this domain of science than carbon-carbon bond-forming reactions. The Grignard, Diels-Alder, and Wittig reactions are but three prominent examples of such processes, and are among those which have undeniably exercised decisive roles in the last century in the emergence of chemical synthesis as we know it today. In the last quarter of the 20th century, a new family of carbon-carbon bond-forming reactions based on transition-metal catalysts evolved as powerful tools in synthesis. Among them, the palladium-catalyzed cross-coupling reactions are the most prominent. In this Review, highlights of a number of selected syntheses are discussed. The examples chosen demonstrate the enormous power of these processes in the art of total synthesis and underscore their future potential in chemical synthesis.

Palladium-catalyzed cross-coupling reactions in total synthesis.

III. Foldamer Research 3910 A. Overview 3910 B. Motivation 3910 C. Methods 3910 D. General Scope 3912 IV. Peptidomimetic Foldamers 3912 A. The R-Peptide Family 3913 1. Peptoids 3913 2. N,N-Linked Oligoureas 3914 3. Oligopyrrolinones 3915 4. Oxazolidin-2-ones 3916 5. Azatides and Azapeptides 3916 B. The â-Peptide Family 3917 1. â-Peptide Foldamers 3917 2. R-Aminoxy Acids 3937 3. Sulfur-Containing â-Peptide Analogues 3937 4. Hydrazino Peptides 3938 C. The γ-Peptide Family 3938 1. γ-Peptide Foldamers 3938 2. Other Members of the γ-Peptide Family 3941 D. The δ-Peptide Family 3941 1. Alkene-Based δ-Amino Acids 3941 2. Carbopeptoids 3941 V. Single-Stranded Abiotic Foldamers 3944 A. Overview 3944 B. Backbones Utilizing Bipyridine Segments 3944 1. Pyridine−Pyrimidines 3944 2. Pyridine−Pyrimidines with Hydrazal Linkers 3945

A field guide to foldamers.

Treatment of triisopropylsilyl enol ethers with eerie ammonium nitrate/sodium azide at −20°C in acetonitrile gives α-azido ketones in average to good yields (50–80%). Subsequent conversion of the α-azido ketones into 2-amino(methoxycarbonyl)cycloalk-2-en-1-ones is described.

Oxidative Addition of Azide Anion to Triisopropylsilyl Enol Ethers: Synthesis of α‐Azido Ketones and 2‐Amino(methoxycarbonyl)alk‐2‐ en‐1‐ones.

New Trialkylsilyl Enol Ether Chemistry. Synthesis of the Benzomorphanone Core Structure Using a Stereoelectronic Conformational Lock.

Methyl (3aR-[3a alpha,4 beta,5 beta,5a beta,9(3R*,5S*,7R*,9R*), 10bR,13a alpha])-4-(acetyloxy)-3a-ethyl-9-[5-ethyl-1,4,5,6,7,8,9, 10-octahydro-5-hydroxy-9-(methoxycarbonyl)-2H-3,7- methanoazacycloundecino[5,4-b]indol-9-yl]-3a,4,5,5a,6,11,12, 13a-octahydro-5-hydroxy-8-methoxy-6-methyl-1H-indolizino-[8,1-c,d] carbazole- 5-carboxylate methanol solvate, C46H58N4O9. 2CH3OH (1), Mr = 875.07, monoclinic, P2(1), a = 10.2759 (12), b = 22.353 (3), c = 10.4051 (12) A, beta = 106.502 (9) degrees, V = 2291.6 (5) A3, Z = 2, Dx = 1.27 g cm-3, Mo K alpha radiation, lambda = 0.7107 A, mu = 0.8397 cm-1, F(000) = 940, T = 198 K, R = 0.0470 for 2751 reflections, Fo greater than or equal to 4 sigma(Fo). The C ring of the vindoline moiety is in the boat conformation with the hydroxy group and the tertiary N in the bowsprit positions resulting in a fairly short intramolecular hydrogen-bonding interaction. The relevant parameters for O3--H3...N9 are O...N 2.651 (6), H...N 1.94 (5) A and O--H...N 147 (5) degrees. The D and E rings are in the sofa and envelope conformations, respectively. The piperidine ring of the catharanthine portion of the molecule assumes the chair conformation while the conformation of the azacyclononene ring is a boat-chair. An intramolecular hydrogen bond between the indolino NH of the catharanthine moiety and methoxy O (O25) of the vindoline moiety is also observed. The relevant parameters for N16'--H16'...O25 are N...O 2.827 (6), H...N2.14 (6) A and O--H...N 136 (5) degrees.

Structure of 18′-Epivinblastine.

The BC-rings of taxol can be synthesized using an intramolecular [5+2]-pyrylium ylide-alkene cyclization, followed by gem -methylcyclopropanation and reductive cleavage of the internal cyclopropane bond.

New Strategy for the Synthesis of the Taxane Diterpenes: Formation of the BC-Rings of Taxol via a (5 + 2) Pyrylium Ylide-Alkene Cyclization, Ring Expansion Strategy.

Philip Magnus

Papers

Oxidative Addition of Azide Anion to Triisopropylsilyl Enol Ethers: Synthesis of α‐Azido Ketones and 2‐Amino(methoxycarbonyl)alk‐2‐ en‐1‐ones.

New Trialkylsilyl Enol Ether Chemistry. Synthesis of the Benzomorphanone Core Structure Using a Stereoelectronic Conformational Lock.

Structure of 18′-Epivinblastine.

New Strategy for the Synthesis of the Taxane Diterpenes: Formation of the BC-Rings of Taxol via a (5 + 2) Pyrylium Ylide-Alkene Cyclization, Ring Expansion Strategy.