Total Synthesis of Diverse Tetramic Acid Bearing cis-Decalin Natural Products

We report herein the first total syntheses of four natural antibiotics, vermisporin, PF1052/AB4015-A, AB4015-L, AB4015-B, and one hydrogenated natural product derivative, AB4015-A2, that all feature a tetramic acid bearing cis-decalin ring. The construction of the functionalized cis-decalin ring was achieved by a diastereoselective intramolecular Diels-Alder (IMDA) reaction, which proceeded via a rare endo-boat transition state. Through an intramolecular neighboring-group-oriented strategy, the sterically hindered epoxy group in vermisporin, PF1052/AB4015-A and AB4015-L was installed efficiently. A one-pot aminolysis/Dieckmann condensation cascade using l -amino acid derivatives afforded the desired tetramic acid structure. The total synthesis led to the unambiguous verification of the absolute configuration of these natural products.     

Advances in Total Synthesis of Some 2,3,5‐Trisubstituted Tetrahydrofuran Natural Products

2,3,5‐Trisubstituted tetrahydrofuran moiety is ubiquitous in natural products. These have served as appealing candidates for total synthesis due to their varied bio‐ and pharmaceutical activities. This tutorial review delineates the ingenious efforts by many researchers in the total synthesis of selected natural products based on a common 2,3,5‐trisubstituted tetrahydrofuran core structure. Many of the syntheses display nuanced interplay between new methods and the ingenuity of planned strategies achieved through catalysis or cascade chemistry. In some cases, the chiron approach has come quite handy, wherein the structural features and the stereochemistry in select molecules could map well with naturally available starting materials. This compilation also aims to enhance the diversity space based on these natural products and further interest in sustainable total synthesis.     

Concise and Efficient Total Syntheses of Alkannin and Shikonin

Two enantiomic natural products with wound-healing properties , alkannin ( 1 ) and shikonin ( 2 ), are accessible by a short and efficient total synthesis. The success was achieved by a novel protecting system for masking of 5,8-dihydroxy-1,4-naphthoquinones (naphthazarins) and a highly stereoselective ketone reduction.     

Current Applications of Suzuki–Miyaura Coupling Reaction in The Total Synthesis of Natural Products: An update

Suzuki‐Miyaura Coupling Reaction (SMCR) has been extensively used in the total synthesis of natural products. We underscored these achievements in a report published in Tetrahedron up to 2012. Since then, there has been tremendous growth in this field and numerous articles have been published after 2012. In this review, we tried to go insight and highlight the current developments in the applications of SMCR as a key and strategic step (steps) in the total synthesis of biologically active natural products accomplished and reported from 2012 till date.     

The Total Synthesis of Diquinane-Containing Natural Products

Diquinane or bicyclo[3.3.0]octane is a conspicuous structural unit existing in the carbo-frameworks of a wide range of natural products such as alkaloids and terpenoids. These diquinane-containing molecules not merely exhibit intriguing architectures, but also showcase a broad spectrum of significant bioactivities, which draw widespread attention from the global synthetic community. During the past decade, with an aim to accomplish the total syntheses of such specified cornucopias of natural products, a variety of elegant strategies for construction of the diquinane ring system have been disclosed. In this Minireview, the achievements on this subject in the timeline from 2010 to June 2020 are demonstrated and it is discussed how the diquinane unit is strategically forged in the context of the specific target structure. In addition, impacts of the selected works to the field of natural product total synthesis is highlighted and the particular outlook of diquinane-containing natural product synthesis is provided.     

Total Synthesis of the Marine Natural Product 7-Deoxy-okadaic Acid: A Potent Inhibitor of Serine/Threonine-Specific Protein Phosphatases

A small change to the structure of okadaic acid ( 1 ), the omission of the single hydroxy group at C7, facilitated substantially the first total synthesis of the derivative 7-deoxyokadaic acid ( 2 ). The conformation of 2 is in agreement with that of 1 and this minimal structural variation has been reported previously to have little effect on the inhibitory activity towards the serine/threonine-specific protein phosphatases PP-1 and PP-2A.     

Total Synthesis of Sanglifehrin A

The immunosuppressive agent sanglifehrin A has been prepared for the first time by total synthesis. The construction of the macrocyclic unit of the target molecule was achieved through a selective intramolecular Stille coupling, and the spirolactam unit by Paterson–aldol reactions. The final steps involve an intermolecular Stille coupling and the opening of the internal acetal unit. This convergent synthesis opens the way for the synthesis of libraries of novel sanglifehrin analogues for biological screening.     

Total Synthesis of the Antiviral Natural Product Houttuynoid B

The first total synthesis of houttuynoid B, a powerful antiviral flavonoid glycoside from the Chinese plant Houttuynia cordata, is described. In a key step, a Baker–Venkataraman rearrangement employing an already glycosylated substrate was used to efficiently set up the fully functionalized carbon skeleton. The required benzofuran building block was prepared through a domino Sonogashira coupling/5‐endo‐dig cyclization and converted into a stable 1‐hydroxybenzotriazole‐derived active ester prior to linking with a galactosylated hydroxyacetophenone unit. The elaborated synthesis requires only nine steps (11 % overall yield) along the longest linear sequence and paves the way for the preparation of structurally related compounds for further biological evaluation.     

Advances in the First Total Synthesis of Natural Flavonoids

Flavonoids, composed of a C₆-C₃-C₆ backbone, are a kind of secondary metabolites of natural medicine, which widely exist in the higher plant. They have received extensive attention from all over the world and obtained rapid development owing to widespread distribution, structural complexity, active diversity, and molecular plasticity. Total synthesis of natural products is not only one of the most driving forces in organic chemistry but also the embodiment of the development level of organic synthesis chemistry. Total synthesis research possesses not only important theoretical significance to the development of organic chemistry but also potential marketing prospects to clinical medicine and significant practical value to the development of natural medicine. Flavonoids contain flavan, chalcone, flavone, biflavone, isoflavone, xanthone, pterocarpin, homoisoflavone, flavonol, favonolignan, and some other main structure types. This article summarizes the latest research on first total synthesis, including the plant sources and biological activities, of these main structure types, so as to provide some reference for both the research of first total synthesis of natural flavonoids and the development and utilization of their medicinal value.     

Total Synthesis of (+)-Gelsedine

A novel iodide-promoted, allene-terminated cyclization of an N-acyliminium ion, a stereoselective Heck spirocyclization, and a chemoselective demethylation at the nitrogen atom of an oxindole are the key transformations in the first total synthesis of the indole alkaloid (+)-gelsedine ( 1 ). This dextrorotatory form of natural gelsedine was formed as a single enantiomer in 21 steps from (S)-malic acid.     

Total Synthesis of the Proposed Structure of (+)-Tolyporphin A O,O-Diacetate

Four monocyclic precursors were assembled in the total synthesis of the proposed structure 1 - A of (+)-tolyporphin A O,O-diacetate (X=Ac). Comparison of the spectroscopic data demonstrated that synthetic tolyporphin O,O-diacetate did not match the O,O-diacetate prepared from natural (+)-tolyporphin A (X=H), calling for a structural revision of this class of natural products. On the basis of a series of NMR experiments including synthetic intermediates, the structure of tolyporphin A is concluded to be 1 - B , in which the configurations of quaternary centers C7 and C17 are opposite to those in the originally proposed structure.     

Applications of Transition‐Metal‐Catalyzed Asymmetric Allylic Substitution in Total Synthesis of Natural Products: An Update

Metal‐catalyzed asymmetric allylic substitution (AAS) reaction is one of the most synthetically useful reactions catalyzed by metal complexes for the formation of carbon‐carbon and carbon‐heteroatom bonds. It comprises the substitution of allylic substrates with a wide range of nucleophiles or S_N2′‐type allylic substitution, which results in the formation of the above‐mentioned bonds with high levels of enantioselective induction. AAS reaction tolerates a broad range of functional groups, thus has been successfully applied in the asymmetric synthesis of a wide range of optically pure compounds. This reaction has been extensively used in the total synthesis of several complex molecules, especially natural products. In this review, we try to highlight the applications of metal (Pd, Ir, Mo, or Cu)‐catalyzed AAS reaction in the total synthesis of the biologically active natural products, as a key step, updating the subject from 2003 till date.     

Corylifolin 的首次全合成

类异戊二烯酚类化合物 Corylifolin(1) 是由 Snapka 等[1]于1998年从豆科植物 Psoralea Corylifolia 中分离得到的天然产物, 其结构已由波谱学和化学方法确定, 一同分离的还有化合物 Bakuchio(2). 植物 Psoralea Corylifolia 是广泛分布于中国和印度的豆科类植物, 药理实验研究表明, 此植物对 Streptococcus 和 Paramecium 等具有很高的活性, 因此它作为民间药材被长期使用. 化合物 Corylifolin(1) 和 Bakuchio(2) 具有类似的化学结构及生物活性, 是有效的DNA复制聚合酶的抑制剂, 而且具有抗肿瘤和抗诱变作用.     

The Total Synthesis of Brevetoxin B: A Twelve-Year Odyssey in Organic Synthesis

The total synthesis of brevetoxin B has been achieved recently after a long search for a suitable pathway. This twelve-year odyssey

1 The Odyssey of Homer, translated by R. Lattimore, Harper Perenial, New York, 1975 . Homer's Odyssey, one of the western world's first two poems (the Iliad is the other), is the tale of the adventures, wanderings, and exploits of Odysseus, a Greek hero of the Trojan war, as he attempts to reach Ithaca, his home island where his wife Penelope awaits him. During his journey Odysseus has an incredible series of adventures and setbacks caused by the anger of the god Poseidon, whose son Odysseus had blinded. Finally, assisted by his patroness, the goddess Athene, Odysseus returns home to Ithaca to find and punish the suitors, evil men who tried to win his wife's hand and who squandered his wealth and corrupted his servants while he was away. Telemachus, Odysseus' son, who had his own share of adventures while growing up, facing the suitors and, looking for his father, joins him in glory and wisdom as they reestablish their throne on Ithaca. Besides Odysseus, other main characters of Odyssey are as follows: Telemachus: The son of Odysseus, who is just entering manhood, is highly conscious of his duties as a prince successor to the throne and protector of his mother as well as the need to live up to his father's reputation as a hero. His actions waver between the immature and the well-thought over as he searches for the truth about his father and desperately appeals to others for help. It is not until towards the end of the story that he exhibits great courage, skills, and confidence and one feels that he is, indeed, the son of Odysseus. Athene: She is the daughter of Zeus, goddess of wisdom, and patroness of arts and crafts. Odysseus is her favorite and protegé and she is his heroine, even though she is a goddess. She plays a leading role in all important events in the narrative, and her spirit and power always influence and assist Odysseus and Telemachus in their difficult moments. A friend and a confidant to Odysseus, she enjoys winning him over and her relationship with him, while the hero adores her and finds special comfort, companionship, and understanding in her. Poseidon: Younger brother to Zeus, god of the sea and of earthquakes, father of Polyphenus the one-eyed Cyclops whom Odysseus blinds. As a ruler of the sea and natural phenomena, Poseidon is able to place many obstacles in front of Odysseus, whom he despises. Poseidon, however, is unable to hold out against the combined pressure of the other gods, particularly Athene, of whom Odysseus is a favorite, and so eventually relents, but not before he repeatedly unleashes his anger. The Cyclops, Scylla, and The Sirens: Some of the superhuman and monstrous characters of the tale who inflicted tremendous tortures and blows at Odysseus and his men, before he finally overcame them. The Suitors: The evil noblemen of Ithaca who attempt to undermine Odysseus, win the hand of his queen, Penelope, and corrupt his palace servants. They succeed partly, wasting away a great deal of Odysseus fortune, but he eventually prevails and punishes them. Ithaca: The island kingdom of Odysseus, most likely located somewhere off the western coast of Greece and the destination of the hero in this adventure. It is interesting to compare places, events, and characters from the Odyssey to those of modern-day total synthesis, an excercise left to the imagination of the reader!

in synthetic organic chemistry was marked by several strategic and tactical routes, and resulted in numerous new synthetic methods. This article is a behind-thescenes account of the total synthesis of brevetoxin B, from its origins at the University of Pennsylvania to its completion at the University of California, San Diego, and The Scripps Research Institute, La Jolla, California.     

Total Synthesis of Carthamin,a Traditional Natural Red Pigment

The first total synthesis of carthamin ( 3 ), a historic natural red pigment, has been achieved. The molecular structure was efficiently constructed by assembling two equivalents of the in situ generated lithiated monomers and triisopropyl orthoformate. This synthesis confirms the structure proposed in 1996.     

Asymmetric Total Synthesis of Fredericamycin A

Seventeen years after the isolation of the promising antitumor antibiotic fredericamycin A, the first asymmetric total synthesis of this compound has been accomplished and thereby its absolute configuration established. The key feature is the regiocontrolled [4+2] cycloaddition of 3 to 2 , which was obtained by the stereospecific rearrangement of 1 . Cp = (−)‐camphanoyl.     

[4 1]及[3 2]会聚式四氢呋喃环合成策略在天然产物全合成中的应用进展

四氢呋喃环广泛存在于具有生物活性的天然产物结构当中,立体选择性地构筑四氢呋喃环往往成为这些天然产物全合成研究中的关键。本文归纳了已有全合成报道中的四氢呋喃环成环策略,以实例展示了其中的会聚式合成策略在近年的发展。相比于直线型的分子内关环策略,以[4+1]、[3+2]为代表的会聚式四氢呋喃关环策略往往能够使全合成的整体路线更加简洁高效,更符合全合成研究领域的发展趋势。     

天然产物goodyeroside A的全合成研究

以5-(S)-(d-盖氧基)-2(5H)-呋喃酮为起始原料．对具有肝保护活性的天然产物goodyeroside A进行了全合成研究。将合成所得目标产物的比旋光值及光谱数据与天然产物的数值相比较，两者一致，证明两者的结构与构型相同。     

The First Total Synthesis of 16-Hydroxygeranylgeraniol

The facile synthesis of 16-hydroxygeranylgeraniol(1), a naturally existing alicyclic diterpene, by alkylation reaction of allylic iodide(3) with phenyl sulfone(4), is described.     

Facile Access to Sterically Hindered Aryl Ketones via Carbonylative Cross-Coupling: Application to the Total Synthesis of Luteolin

A general and mild protocol for achieving the carbonylative cross-coupling of sterically hindered, ortho-disubstituted aryl ketones is reported. The commercially available PEPPSI-IPr catalyst is shown to efficiently promote the carbonylative cross-coupling of hindered ortho-disubstituted aryl iodides to give diaryl ketones; traditional phosphine catalysts are less effective. Carbonylative Suzuki-Miyaura cross-couplings provide a diverse array of biaryl ketones in good to excellent yields. The same catalyst is also shown to catalyze a carbonylative Negishi cross-coupling reaction, utilizing a variety of alkynyl-zinc reagents to give the corresponding alkynyl aryl ketones. Application of this new methodology to the synthesis of the natural product luteolin is reported.