Framework Of Natural Products Research Articles

Synthesis of the B-seco limonoid core scaffold.

Synthetic investigations towards the structurally complex and highly decorated framework of B-seco limonoid natural products by means of a [3,3]-sigmatropic rearrangement are described. Detailed model studies reveal, that an Ireland–Claisen rearrangement can be employed to construct the central C9–C10 bond thereby giving access to the B-seco limonoid scaffold. However, application of the developed strategy ended up failing in more complex and sterically demanding systems.

Diastereoselective aldol reactions and applications to various natural product frameworks

Research in our lab has shown that lithium enolate additions to chloroaldehydes occurs selectively to yield predominantly anti-ketochlorohydrins (1). These enantioenriched building blocks can be further functionalized to provide scaffolds for various natural products; this includes reduction and cyclization to yield substituted tetrahydrofuranols (2) or radical dehalogenation to produce asymmetric hydroxyketone moieties (3). Research presented will include enantioselective synthesis of natural products Laurefurenynes A and B (4) and Solistatin (5) using this recently developed methodology.

A biomimetic synthesis of (−)-ascorbyl phloroglucinol and studies toward the construction of ascorbyl-modified catechin natural products and analogues

A method for appending the ascorbyl moiety onto the framework of phenolic natural products has been developed. This reaction proceeds in two steps from l-ascorbic acid and employs acetic acid catalysis. Excellent stereoselectivity is observed during C–C bond formation between the phenolic compound and dehydroascorbic acid, and the process is also chemoselective for phenol derivatives bearing electron-donating substituents in each of the 1, 3, and 5 positions. Further, good regioselectivity was also observed when phenols lacking an axis of C 2 symmetry were employed. This method has led to the synthesis of (−)-ascorbyl phloroglucinol as well as the tetracyclic core of ascorbyl-modified catechin natural products.

A Simple and General Platform for Generating Stereochemically Complex Polyene Frameworks by Iterative Cross‐Coupling

A Simple and General Platform for Generating Stereochemically Complex Polyene Frameworks by Iterative Cross‐Coupling

An approach to the synthesis of dimeric resveratrol natural products via a palladium-catalyzed domino reaction

A route for the rapid assembly of the carbon framework of several resveratrol natural products is presented. A palladium-catalyzed domino reaction of bromostilbene derivative 6 and tolane 7, involving two sequential Heck coupling reactions, provides access to the benzofulvene-based core of various resveratrol-derived natural products. The carbon skeleton of pallidol and its congeners is achieved by a Lewis acid-induced Nazarov-type oxidative cyclization of 9.

Highly Stereoselective Aldol Reactions in the Total Syntheses of Complex Natural Products

More than ever, it is a challenging objective in synthetic chemistryto create efficient access to biologically active compounds. Inparticular, one structural element which is frequently incorporatedin the framework of complex natural products is a β-hydroxyketone. In this context, the aldol reaction as the most importanttransformation to generate this structural element not only createsnew C-C bonds but also establishes stereogenic centers.In recent years, a large variety of highly selective methodologiesfor aldol and aldol-type reactions has been put forward. On thisbackground, the vinylogous Mukaiyama aldol reaction became a pivotal transformationsince it also allows for the immediate transformation of the olefinwhich is simultaneously introduced. This Account covers the applicationof various (vinylogous) aldol reactions from our laboratories inthe syntheses of natural products with important bio-logical activities. 1 Introduction 2 Polyketides: Selected Natural Products 3 Vinylogous Mukaiyama Aldol Reaction (VMAR) 3.1 Triarylboranes in the Substrate-Controlled VMAR in the Synthesisof Ratjadone 3.1.1 Suppression of the Silyl Cation Catalyzed Pathway 3.1.2 Substrate-Controlled VMAR in the Synthesis of Oleandolide 3.1.3 Substrate-Controlled VMAR in the Synthesis of Amphidi-nolideH2 and Tedanolide 3.2 Oxazaborolidinones as Chiral Lewis Acids in the Enantio-selectiveVMAR 4 Aldol Reactions in Natural Product Syntheses 4.1 Tedanolide 4.2 Chivosazole 4.3 Disorazole 4.4 Epothilone 4.5 Spirangien 5 Conclusions and Outlook

Virescenols: Sources, Structures and Chemistry

This review provides the first overview on the isolation and structure elucidation of a class of isopimaric diterpenes: virescenols. An important part of this review deals with the structural modifications of virescenols leading to several different natural product frameworks.

Rapid access to polyprenylated phloroglucinols via alkylative dearomatization-annulation: total synthesis of (+/-)-clusianone(1).

A concise approach to the bicyclo[3.3.1]nonane framework of the polyprenylated phloroglucinol natural products utilizing a tandem alkylative dearomatization−annulation sequence is described. Syntheses of (±)-clusianone and a complex adamantane framework have been achieved using the developed methodology.

A Highly Selective Rearrangement of a Housane-Derived Cation Radical: An Electrochemically Mediated Transformation

To utilize housane-derived cation radicals as intermediates for the synthesis of the bicyclo (n.3.0) framework of natural products, a highly regioselective [1,2] shift of carbon to either a radical or an electron-deficient site is required. Herein we describe how this has been accomplished, provide a set of guidelines to assess housane oxidizability prior to its synthesis, and describe a synthesis of housane 18 that capitalizes upon the facility of [1,5] hydrogen shifts in substituted cyclopentadienes. The catalytic electrochemically mediated oxidation of 18 leads to a cation radical that engages in a rearrangement leading to the (4.3.0) adduct 23. The appearance of a catalytic current in the cyclic voltammogram of a solution containing the tris(aryl)amine and housane 18 is an excellent indicator that the amminium cation radical 14*+ is able to oxidize the housane and return the mediator to the original redox couple. DFT calculations show electron density on both the aryl and strained sigma framework in the HOMO of housane 18. From the spin density and electrostatic potential map for the cation radical, a picture where the spin resides on the side that is distal to the substituent emerges, while the hole is proximal to it. Both experiment and theory show that the rearrangement is best characterized as a [1,2] carbon shift toward an electron-deficient site and that migration toward the substituent-bearing carbon is much preferred over the alternative pathway.

An enyne metathesis/Diels–Alder reaction sequence towards the synthesis of cup-shaped 5/5/6-tricyclic architectures

A strategy to synthesize the 5/5/6-tricyclic framework of presilphiperfolane natural products is described, involving a model dienyne compound ( I). The key steps are an enyne metathesis reaction to introduce the diene part and a Diels–Alder cycloaddition to reveal the tricyclic architecture.

Efficient Method for Synthesis of Angucyclinone Antibiotics via Gold-Catalyzed Intramolecular [4 + 2] Benzannulation: Enantioselective Total Synthesis of (+)-Ochromycinone and (+)-Rubiginone B2

[reaction: see text] An efficient synthetic approach to angucyclinone antibiotics, (+)-ochromycinone and (+)-rubiginone B(2), is reported. The key step involves the facile formation of 2,3-dihydrophenantren-4(1H)-one skeleton, an important framework of angucyclinone natural products, by using gold-catalyzed intramolecular [4 + 2] benzannulation reaction.

Synthesis of Epoxyquinol A and Related Molecules: Probing Chemical Reactivity of Epoxyquinol Dimers and 2H-Pyran Precursors

Total syntheses of the epoxyquinoid dimers, epoxyquinols A, B, and epoxytwinol A (RKB-3564 D), have been accomplished employing [4 + 2] and [4 + 4] dimerization of 2H-pyran epoxyquinol monomers. Modifications of 2H-pyran precursors have been explored, including alteration of epoxy alcohol and diene stereochemistry. A stable 2H-pyran prepared by alteration of the epoxyquinol 2H-pyran nucleus was evaluated as a diene in Diels-Alder cycloaddition with reactive dienophiles. Extensive studies for improving the [4 + 4] dimerization of selectively protected 2H-pyran monomers to afford the novel epoxyquinoid dimer epoxytwinol A were carried out, and valuable insight regarding competitive [4 + 2] and [4 + 4] dimerization processes has been obtained. In addition, chemical reactivities and structural modifications of epoxyquinol dimers have been evaluated, including [2 + 2] photocycloaddition and [3,3] sigmatropic rearrangement, indicating the possibility for production of novel structural diversity from dimeric epoxyquinoid natural product frameworks.

Pyrano[2,3‐b]dioxanes through Bisacetalic Annulation of 2‐Ketosugars to Glycol

AbstractThe utility of 2‐ketohexosyl (“ulosyl”) bromides has been extended to the straightforward generation of cis‐fused pyrano[2,3‐b]dioxanes (1,4,5‐trioxadecalins) of type 11 and 13 by β‐specific and α‐selective glycosidation with glycol, and subsequent intramolecular hemiketalization. Mild basic conditions elicit highly stereoselective rearrangements to trioxadecalinones 22−25, representing the structurally and configurationally correct framework of steroidal natural products in which the sugar portion is doubly glycosidically linked to the aglycon. Exposure of 11 or 13 to mineral acid results in an essentially stereospecific contraction of the pyranoid ring to yield trioxaspiro[4,5]decanes. Mechanistic considerations of the unusual rearrangements observed are discussed in light of available experimental facts and the scarce existing analogies. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Tandem Enyne Metathesis‐Diels—Alder Reaction for Construction of Natural Product Frameworks.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of novel antitumor agent 1-methoxy-5,10- dioxo-5,10-dihydro-1H-benzo[g]isochromene carboxylic acid (3-dimethylylaminopropyl)amide with a dual role Pd(II) catalyst.

A convenient and simple method for the synthesis of 1-methoxy-5,10-dioxo-5,10-dihydro-1H-benzo[g]isochromene-3-carboxylic acid (3-(dimethylamino)propyl)amide 4c was developed. The key step involves the easy formation of 1,3-disubstituted cyclic alkenyl ether, an important framework of isochromene natural products, with a dual role Pd(II) catalyst.

First Total Synthesis of (‐)‐AL‐2.

Treatment of the 3,4-dioxygenated-9-hydroxy-1-nonyn-5-one derivative, derived from diethyl l-tartrate, with a palladium catalyst in methanol under a CO atmosphere effected an intramolecular acetalization and a stereoselective construction of the (E)-methoxycarbonylmethylidene functionality resulting in formation of the core framework of the diacetylenic spiroacetal enol ether natural products. Chemical transformations of the 1,6-dioxaspiro[4.5]decane derivative thus formed led to the first total synthesis of (-)-AL-2. [reaction: see text]

First total synthesis of (-)-AL-2.

Treatment of the 3,4-dioxygenated-9-hydroxy-1-nonyn-5-one derivative, derived from diethyl l-tartrate, with a palladium catalyst in methanol under a CO atmosphere effected an intramolecular acetalization and a stereoselective construction of the (E)-methoxycarbonylmethylidene functionality resulting in formation of the core framework of the diacetylenic spiroacetal enol ether natural products. Chemical transformations of the 1,6-dioxaspiro[4.5]decane derivative thus formed led to the first total synthesis of (-)-AL-2. [reaction: see text]