Tetracyclic Framework Research Articles

First macrocycle based on chlorin and isosteviol structural elements

Acylation by suberic acid chloride of chlorin with two oximated isosteviol groups on its periphery produced for the first time a macrocyclic system containing a porphyrin ring and two tetracyclic ent-beyerane frameworks.

One-Pot Synthesis of Fused-Tetracyclic Scaffolds Employing a Lewis Acid Promoted Domino Reaction of Naphthoquinones

The facile synthesis of tetracyclic molecular frameworks employing a Lewis acid promoted domino reaction of naphthoquinones with hydroxy- and amino-functionalized cross-conjugated trienes is reported. The reaction cascade involves a heterocyclization via hemiacetal or imine formation, and an intramolecular Diels­-Alder cycloaddition.

Oxime Derivatives as α-Electrophiles. From α-Tetralone Oximes to Tetracyclic Frameworks

When subjected to the conditions of a Semmler-Wolff/Schroeter aromatization, the oximes of 4-benzyl-substituted tetralones undergo an electrophilic aromatic substitution reaction to form tetracyclic frameworks.

A pattern recognition approach to 14- epi-hydrophenanthrene core of the morphine alkaloids based on shikimic acid

An expeditious and stereoselective construction of C-14-epimer of the tetracyclic hydrophenanthrene framework of the morphine alkaloids is described. The core structure is obtained in nine steps in 11% overall yield from shikimic acid via three key transformations: (i) coupling of shikimic acid with 2-iodoisovanillin at C-3 by double S N2 inversion to form the aryl ether 5; (ii) an intramolecular Heck reaction to construct the dihydrobenzofuran ring and (iii) a McMurry coupling to furnish the hydrophenanthrene core.

Total Synthesis of (±)-Meloscine

The total synthesis of (±)-meloscine was completed in a highly stereoselective manner starting from the known 4-(2-aminophenyl)-2,3-dihydro-N-methoxycarbonylpyrrole. The crucial step in this total synthesis involves the efficient construction of the tetracyclic framework of the target natural product by the intramolecular Pauson-Khand reaction.

ChemInform Abstract: Promising Antimicrobial Agents: Synthetic Approaches to Novel Tricyclic and Tetracyclic Pyrimidinones with Antimicrobial Properties.

AbstractVarious new compounds containing a thiazolopyrimidine scaffold as part of a tricyclic or tetracyclic framework are synthesized and evaluated for their antibacterial and antifungal activities.

Total synthesis of (+)-isatisine A.

Total synthesis of (+)-isatisine A is described based on the application of a silyl-directed Mukaiyama-type [3 + 2]-annulation for the preparation of a fully substituted furan core. The indole branch forming the quaternary carbon center at C2 was constructed by addition to an intermediate N-acyliminium ion derived from aminal 4. In addition, the fused tetracyclic framework including furan core was built up using modified Buchwald amidation conditions.

Synthesis of the Tetracyclic Core of Tetrapetalone A Enabled by a Pyrrole Reductive Alkyation

The tetracyclic framework of the tetrapetalone A aglycon has been secured through synthesis. A reductive pyrrole alkylation enables the formation of a key tetrasubstituted carbon stereocenter, and the tetramic acid portion of the molecule can be accessed through silicon or boronic ester conjugate addition to an ene-lactam.

ChemInform Abstract: Enantiospecific, Biosynthetically Inspired Formal Total Synthesis of (+)‐Liphagal (VII).

AbstractKey feature of the title synthesis is a ring expansion of a fused 6,6‐ring system via stereoselective epoxide ring opening and combined recyclization—furan ring closure to build the tetracyclic framework (VI).

ChemInform Abstract: A Marine Diterpene with a Novel Tetracyclic Framework from the West Indian Gorgonian Octocoral Pseudopterogorgia elisabethae.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Simple and One‐Pot Synthesis of Tri‐ and Tetracyclic Frameworks Containing [1,8]Naphthyridin‐2‐one Moiety from the Baylis—Hillman Adducts.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Multi-chelation approach towards natural product-like skeletons: one-pot access to a nitrogen-containing tetracyclic framework from AlaAla dipeptide

Reductive transformation of the dipeptide BocAlaAlaOMe to a complex, internally charge-stabilized, natural product-like skeleton in one synthetic step is discussed. Stepwise replacement of the B-H bonds in borane by B-N or B-O resulted in incorporation of three boron atoms in a tetracyclic framework whereby one is stereogenic!

Total synthesis of all (-)-Agelastatin alkaloids.

The pyrrole-imidazole family of marine alkaloids, derived from linear clathrodin-like precursors, constitutes a diverse array of structurally complex natural products. The bioactive agelastatins are members of this family that possess a tetracyclic molecular framework incorporating C4-C8 and C7-N12 bond connectivities. We provide a hypothesis for the formation of the unique agelastatin architecture that maximally exploits the intrinsic chemistry of plausible biosynthetic precursors. We report the concise enantioselective total syntheses of all known agelastatin alkaloids including the first total syntheses of agelastatins C, D, E, and F. Our gram-scale chemical synthesis of agelastatin A was inspired by our hypothesis for the biogenesis of the cyclopentane C-ring and required the development of new transformations including an imidazolone-forming annulation reaction and a carbohydroxylative trapping of imidazolones.

Simple and one-pot synthesis of tri and tetracyclic frameworks containing [1,8]naphthyridin-2-one moiety from the Baylis–Hillman adducts

A facile synthesis of tri and tetracyclic frameworks containing [1,8]naphthyridin-2-one skeleton from the Baylis–Hillman alcohols via the Johnson–Claisen rearrangement, followed by the treatment with Fe/AcOH in simple one-pot multi-step process is described.

Nine-Step Enantioselective Total Synthesis of (+)-Minfiensine

An enantioselective total synthesis of the Strychnos alkaloid (+)-minfiensine has been accomplished. Prominent features of this synthesis include (i) a new enantioselective organocatalytic Diels-Alder/amine cyclization sequence to build the central tetracyclic pyrroloindoline framework in four steps from commercial materials and (ii) a 6-exo-dig radical cyclization to forge the final piperidinyl ring system. This total synthesis of (+)-minfiensine was completed in nine chemical steps and 21% overall yield.

Solid-State Melt Reaction for the Domino Process: Highly Efficient Synthesis of Fused Tetracyclic Chromenopyran Pyrimidinediones Using Baylis−Hillman Derivatives

A solid-state melt reaction (SSMR) has been demonstrated via a domino process for the synthesis of tetracyclic chromenopyran pyrimidinedione frameworks using Baylis-Hillman derivatives through in situ formation of an olefin followed by an intramolecular [4 + 2] cycloaddition reaction sequence. The tetracyclic frameworks were obtained without using catalyst and solvent in a highly stereoselective and stereospecific fashion. The isolated yield is excellent and does not require column chromatography purification to obtain the pure product.

Cycloaddition of annulated cyclohexa-2,4-dienones and novel reduction of halogen at bridgehead: an expedient route to tetracyclo[6.5.2.0 2,7.0 9,13]pentadec-2(7),11-dien-14-one and framework of conidiogenol and conidiogenone

An expedient route to tetracyclo[6.5.2.0 2,7.0 9,13]pentadec-2(7),11-dien-14-one and tetracyclic framework of conidiogenol have been reported. Cycloaddition of annulated cyclohexa-2,4-dienone with cyclopentadiene, photochemical oxa-di-π-methane reaction and a highly unusual dehalogenation of bridgehead halogen are the key features of our methodology.

Sequential One-Pot Cyclizations: Concise Access to the ABCE Tetracyclic Framework of Strychnos Alkaloids

A sequential one-pot biscyclization route to the ABCE tetracyclic framework of Strychnos alkaloids has been developed. Specifically, the AgOTf-mediated spirocyclization of an appropriately functionalized indole 3-carbinamide afforded a stable spiroindolenine intermediate; subsequent addition of DBU to the reaction mixture effected an unprecedented intramolecular aza-Baylis-Hillman reaction, delivering a tetracyclic product in 70% isolated yield.

Strategies for the Total Synthesis of C2−C11 Cyclized Cembranoids

The C2-C11 cyclized cembranoids, which include the eunicellins (also known as the cladiellins), briarellins, asbestinins, and sarcodictyins, are secondary metabolites isolated from gorgonian octocorals and soft corals. An unusual oxatricyclic ring system containing a hydroisobenzofuran and an oxonene unit with stereogenic centers residing at C1-3, 9, 10, and 14 is common to the eunicellins, briarellins, and asbestinins. However, the location of the cyclohexyl methyl groups (C11 versus C12) and the oxidation level of the sixand nine-membered rings differ among the three classes. Faulkner has proposed that the cyclization of the cembranoid diterpene skeleton initiates a biosynthetic pathway that leads to all four subclasses of these unusual molecules (Figure 1). Beginning with the cembrane skeleton, C2-C11 cyclization provides the cladiellin framework. An intramolecular etherification of the cladiellin tricycle affords the tetracyclic framework of the briarellin subclass, and a subsequent 1,2-suprafacial methyl shift of the briarellin structure is postulated to deliver the asbestinins as the class that is furthest evolved from the cembrane skeleton. The presence of multiple structural types in a common organism provides circumstantial evidence for Faulkner’s proposed biosynthetic pathway. The isolation of a cembrane metabolite with cladiellin metabolites in Alcyonium molle and with asbestinin metabolites in Briareum steckii are specific examples. The sarcodictyins are also proposed to arise from a C2-C11 cyclization of the cembrane skeleton; however, in these systems, the cyclization results in a fused cyclohexane and oxonane in place of the hydroisobenzofuran of the cladiellins, briarellins, and asbestinins. As a result of this significant structural variation of the sarcodictyins, the synthetic approaches to these molecules are quite different than those for the other three related subclasses. This review will cover efforts toward the eunicellins, briarellins, and asbestinins but will not cover efforts toward the total synthesis of the sarcodictyins. Eunicellin was the first reported member of the C2-C11 cyclized cembranoid natural products, isolated in 1968 by Djerassi and co-workers from the soft coral Eunicella stricta found off the coast of Banyuls-sur-Mer in France. Since this discovery, over 100 unique secondary metabolites of gorgonian octocorals have been characterized, including the first asbestinin in 1980 and the first briarellin in 1995. A wide range of structural diversity is displayed by this group of marine natural products. The natural role of these cembranoids is proposed, based upon mollusk and fish lethality assays, to involve predation deterrence. Upon further investigation, several of the members of these subclasses have demonstrated significant pharmacological potential. Particularly, these diterpenes have been shown to exhibit in vitro cytotoxicity against various cancer cell lines, anti-inflammatory properties, antimicrobial activities, and histamine and acetylcholine antagonism. The fascinating molecular architecture of these cembranoids, as well as their potential as therapeutic agents, has sparked much interest in the synthetic community over the past decade. A variety of approaches toward these challenging structural motifs have been investigated and several total syntheses have been accomplished. Efforts toward the total synthesis of the cladiellins, briarellins, and asbestinins are the subject of this review.

Expedient Synthesis of 6-Aryl Derivatives of 3,4-Dihydro-1,4,4a,6a-tetraaza-benzo[a]fluoren-2-one: A New Heterocyclic Framework

3,4-Dihydro-1,4,4a,6a-tetraaza-benzo[a]fluoren-2-one, a new tetracyclic heterocyclic framework, is designed through a simple and convenient synthetic sequence. Its 6-aryl derivatives are synthesized starting from 1H-indole-2-carboxylic acid. The reaction of differently substituted phenacyl bromides with 1H-indole-2-carboxylic acid and POCl3-mediated cyclization of the resultant 1H-indole-2-carboxylic acid phenacyl ester provided 2-oxa-4a-aza-fluoren-1-one, and its sequential reaction with hydrazine and 2-chloro-acetamide furnished the desired new heterocyclic compounds 7a–f.