Synthetic studies toward melotenine A

Attempts to the construction of B/C ring and E ring in melotenine A are described. Based on para-dienone chemistry, a tactical application of tandem aminolysis/aza-Michael addition reaction was made to access highly functionalized building blocks with the pyrrolo[2,3-d]carbazole tetracyclic unit (A/B/C/D ring). Albeit negative results for assembling the dihydroazepine unit (E ring) by using the proposed fragmentation reaction of gem-dihalocyclopropanes, an alternative strategy based on ring closing metathesis was evolved to forge the E ring possessing a twisted 1,3-diene unit embedded in the rigid skeleton of melotenine A.     

Synthesis of ACE tricyclic systems of daphnicyclidin A and dehy-droxymacropodumine A

The synthesis of the ACE tricyclic system of daphnicyclidin A and dehydroxymacropodumine A are developed. The key reactions include an efficient aldol reaction to introduce chiral fragment 33 for further construction of piperidine ring B and seven-membered ring C, a nucleophilic addition of lithium pentene to aldehyde for installation of ring E, and a photocatalytic decarboxylation conjugate addition to construct ring C.     

A Topological Approach to the Problem of Ring Structures

In the mechanized documentation of chemical literature, the definition of structural concept is very important. The usual for definitions for ring structures are inadequate. Essential ring structures are sometimes not recognized on the basis of these definitions and are therefore missed in a literature search. This is particularly true of bridged ring systems. The ring concept and ring condensation types are now redefined on a topological basis in the closest possible analogy to the intuitive approach of the chemist. In complicated molecular structures, these “fundamental rings” can be easily determined, either manually or by means of a programmed computer. The concept of the “ring complex” is defined and suggested as a preliminary screen in literature searches for ring structures. This will save machine time, and so reduce the cost of searches.     

A redox-switchable alpha-cyclodextrin-based [2]rotaxane

A bistable [2]rotaxane comprising an alpha-cyclodextrin (alpha-CD) ring and a dumbbell component containing a redox-active tetrathiafulvalene (TTF) ring system within its rod section has been synthesized using the Cu(I)-catalyzed azide-alkyne cycloaddition, and the redox-driven movements of the alpha-CD ring between the TTF and newly formed triazole ring systems have been elucidated. Microcalorimetric titrations on model complexes suggested that the alpha-CD ring prefers to reside on the TTF rather than on the triazole ring system by at least an order of magnitude. The fact that this situation does pertain in the bistable [2]rotaxane has not only been established quantitatively by electrochemical experiments and backed up by spectroscopic and chiroptical measurements but also been confirmed semiquantitatively by the recording of numerous cyclic voltammograms which point, along with the use of redox-active chemical reagents, to a mechanism of switching that involves the oxidation of the neutral TTF ring system to either its radical cationic (TTF*+) or dicationic (TTF2+) counterparts, whereupon the alpha-CD ring, moves along the dumbbell to encircle the triazole ring system. Since redox control by both chemical and electrochemical means is reversible, the switching by the bistable [2]rotaxane can be reversed on reduction of the TTF*+ or TTF2+ back to being a neutral TTF.     

A diastereoselective total synthesis of trans-trikentrin A: a ring contraction approach

A new route to obtain the polyalkylated indole (+/-)-trans-trikentrin A was developed. The synthesis of this natural alkaloid features a thallium(III)-mediated ring contraction reaction to obtain the trans-1,3-disubstituted five-membered ring in a diastereoselective manner. Thallium(III) is chemoselective in this rearrangement, reacting with the olefin without oxidation of the indole moiety. Other key transformations are the Bartoli's reaction to construct the heterocyclic ring and a Heck coupling to add the carbons atom that will originate the nonaromatic cycle.     

A ring opening reaction of benzisothiazolones. A new route to unsymmetrical disulfides

A series of unsymmetrical disulfides has been prepared by employing a reaction involving a ring opening, nucleophilic attack of a thiol on a 1,2-benzisothiazol-3-one. The benzisothiazolones were in turn prepared by an intramolecular ring closure of an amide on a sulfenyl thiocarbonate. The sulfenyl esters were synthesized as intermediates for preparing mixed-disulfides, but the benzisothiazolone ring closure occurred spontaneously. It was initially thought that the mixed-disulfides were being formed from the sulfenyl ester, but the isolation and stepwise reaction of the benzisothiazolones provided proof for the reaction mechanism.     

双哌啶基二硫化物的动态NMR的研究

双取代哌啶基二硫化物的动态^1H NMR谱的研究表明,分子内哌啶环的翻转活化自由能较哌啶有显著增加,△G值为71.43±0.25-73.27±0.46kJ.mol^-^1,同时观察到双哌啶基二硫化物分子内哌啶环的3,4,5-位所在平面的翻转,比1,2,6-位所有在平面约快四倍,△G值低3.62kJ.mol^-^1;这充分显示了分子中N原子上带有较大基团的影响.比较双哌啶基二硫化物与相应三硫化物的环翻转能垒,也显示出空间障碍的影响.     

A Pauson-Khand and ring-expansion approach to the aquariane ring system

[Structure: see text] The carbocyclic ring system of the aquariolide diterpenes has been synthesized by two routes involving a diastereoselective Pauson-Khand reaction and subsequent ring expansion. In one route, a tetracyclic enone was elaborated to generate the nine-membered ring by Grob fragmentation. In the second approach, a spirocyclic tricycle underwent a facile anionic oxy-Cope rearrangement to complete the synthesis of the desired ring system.     

STRUCTURE OF A THYMINE-THYMINE ADDUCT FORMED BY MENADIONE PHOTOSENSITIZATION

Abstract— The structure of one of the dithymine adducts formed by near-UV photosensitization of aqueous oxygenated thymine in the presence of 2-methyl- 1, 4-naphthoquinone is reported. The compound, 6'β-hydroxy-5'β-1 - [5-methylpyrimidinyl- 2,4-dione]-5'-6'-dihydrothymine has one thymine ring (ring I) linked through the 1-nitrogen atom to the C5' atom of a second thymine, which has been hydroxylated af C6' (ring II). Crystals are monoclinic, space group 12/c, and the structure was refined to R_obs= 0.036 for 2072 unique reflections with intensities I greater than 2.33(I). Ring I is planar, whereas ring II is not. Ring I and the OH group on ring II are cis to ring II. The planar ring I and the OH group are attached, respectively, in an equatorial and axial manner to ring II (which is in the sofa conformation). The planar rings I of close-lying pairs of molecules stack parallel to each other. The structure is held together by a hydrogen-bonding system consisting of the water molecules, the NH groups, two of the C=O groups and the OH group. The chemical formula and relative configurations at C5' and C6 are established by this analysis.     

A novel approach to ring A analogues of the marine pyridoacridine alkaloid ascididemin

A novel approach to ring A analogues of the marine pyridoacridine alkaloid ascididemin starting from readily available 4-bromobenzo[c][2,7]naphthyridine (10) comprises a high-yield Minisci-type homolytic methoxycarbonylation at C-5, followed by introduction of the ring A scaffold via Suzuki cross-coupling reaction, and a trifluoromethanesulfonic acid-aided Friedel–Crafts-type intramolecular acylation. This protocol allows for the introduction of various electron-rich carbocyclic and heterocyclic ring A substitutes.     

Enantioselective Total Synthesis of (+)‐Ophiobolin A

The enantioselective total synthesis of (+)‐ophiobolin A is described. This total synthesis features the construction of the spiro CD ring of (+)‐ophiobolin A through a stereoselective intramolecular Hosomi–Sakurai cyclization reaction, the joining of the A ring to the CD ring by using a reaction reported by Utimoto, and the construction of the ophiobolin eight‐membered carbocyclic ring through ring‐closing metathesis (RCM), which was performed for the first time in this study. This successful RCM reaction required the use of a substrate that contained either a benzyloxy or a methoxymethoxy group at the C5 position and either an isopropenyl group or its hydroxylated form at the C6 position.     

A shuttling molecular machine with reversible brake function

Design, synthesis, and demonstration of a prototype of a shuttling molecular machine with a reversible brake function are reported. It is a photochemically and thermally reactive rotaxane composed of a dianthrylethane-based macrocycle as the ring component and a dumbbell shaped molecular unit with two, secondary ammonium stations separated by a phenylene spacer as the axle component. The rate of shuttling motion was shown to be reduced to less than 1 % (from 340 to <2.5 s(-1)) by reducing the size of the ring component from 30-crown-8 to 24-crown-8 macrocycles upon photoirradiation. The ring component was turned back to 30-crown-8 by thermal ring opening, thus establishing a reversible brake function that works in response to photochemical and thermal stimuli.     

Total synthesis of antimalarial diterpenoid (+)-kalihinol A

Total synthesis of antimalarial diterpenoid (+)-kalihinol A, isolated from marine sponge Acanthella sp., is achieved. This total synthesis involves regioselective alkylation of an epoxide, construction of a tetrahydropyran ring by iodo-etherification, construction of a cis-decalin ring by intramolecular Diels-Alder reaction, isomerization of cis-decalin to trans-decalin, and subsequent functionalization of the trans-decalin ring.     

A new ring expansion for a chiral hexahydroazulene skeleton possessing an angular methyl group

A new synthetic route for a pseudoguaiane ring system is described. The synthesis features an Ireland-Claisen rearrangement for constructing the trans-fused ring system, followed by a new ring expansion to yield a bicyclo[5.3.0]decane ring system possessing an angular methyl group.     

Stereoselective synthesis and cyclisation of the acyclic precursor to auripyrone A and B

The acyclic precursor to the auripyrones has been synthesized by a stereoselective aldol strategy. This compound fails to undergo cyclisation to form the spiroacetal dihydropyrone ring system found in auripyrone A and B; instead, it forms a dihydropyrone ring by cyclisation of the C11 hydroxyl onto the C15 carbonyl with subsequent dehydration. In contrast, a model compound was prepared and shown to cyclise to both the spiroacetal dihydropyrone ring system and the dihydropyrone ring.     

Total Synthesis and Biological Evaluation of (+)‐Gambieric Acid A and Its Analogues

In this study, we report the first total synthesis and complete stereostructure of gambieric acid A, a potent antifungal polycyclic ether metabolite, in detail. The A/B‐ring exocyclic enol ether 32 was prepared through a Suzuki–Miyaura coupling of the B‐ring vinyl iodide 18 and the alkylborate 33 and subsequent closure of the A‐ring by using diastereoselective bromoetherification as the key transformation. Suzuki–Miyaura coupling of 32 with acetate‐derived enol phosphate 49 , followed by ring‐closing metathesis of the derived diene, produced the D‐ring. Subsequent closure of the C‐ring through a mixed thioacetalization completed the synthesis of the A/BCD‐ring fragment 8 . The A/BCD‐ and F′GHIJ‐ring fragments (i.e., 8 and 9 ) were assembled through Suzuki–Miyaura coupling. The C25 stereogenic center was elaborated by exploiting the intrinsic conformational property of the seven‐membered F′‐ring. After the oxidative cleavage of the F′‐ring, the E‐ring was formed as a cyclic mixed thioacetal (i.e., 70 ) and then stereoselectively allylated by using glycosylation chemistry. Ring‐closing metathesis of the diene 3 thus obtained closed the F‐ring and completed the polycyclic ether skeleton. Finally, the J‐ring side chain was introduced by using a Julia–Kocienski olefination in the presence of CeCl₃ to complete the total synthesis of gambieric acid A ( 1 ), thereby unambiguously establishing its complete stereostructure. The present total synthesis enabled us to evaluate the antifungal and antiproliferative activities of 1 and several synthetic analogues.     

SYNTHESIS AND CONFORMATIONAL STUDIES OF A NUMBER OF SATURATED BICYCLIC SIX-MEMBERED RING PHOSPHITES

Abstract

An ¹H NMR study of the conformation of the dioxaphosphorinane ring of a number of diastereoisomeric bicyclic saturated six-membered ring phosphites (3ab-10ab) has been performed. The dioxaphosphorinane ring of these phosphites is transannelated with a tetrahydrofuran, cyclopen-tane, tetrahydropyran or cyclohexane ring. The substituent on the phosphorus atom is a methoxy or phenoxy group. It is shown that the cis isomers 3a-10a prefer a chair conformation of the dioxaphosphorinane ring, independent of the substituent on the phosphorus atom and of the nature of the transannelated ring. In contrast, for the trans isomers 3b-10b a twist rather than a chair conformation of the dioxaphosphorinane ring is preferred. The fraction of the twist conformer in the trans isomers is mainly determined by the substituent on phosphorus. The size and composition of the transannelated ring are relatively unimportant in this respect. For both cis and trans isomers the preferred geometry is solvent-independent. The measured ^3JPOCH couplings of the cis isomers 3a-10a are used to formulate an expression for the dependence of such couplings upon dihedral angles in bicyclic phosphites.     

A Diaminopillar[5]arene-Based Macrobicyclic Molecule: Synthesis,Characterization and A Lock–Key Story

A new macrobicyclic molecule ( BC-DAP5 ), consisting of a diaminopillar[5]arene cavity and a fused ring, was successfully constructed using a Grubbs metathesis reaction. Further studies indicated that BC-DAP5 possessed a unique molecular behavior, showing a response to acid/base stimuli. In BC-DAP5 , protons (acid) acted as a lock, locking the fused ring out of the cavity (pillar[5]arene), and a base served as the key, making the fused ring switch in or out freely. Reversible control of the molecular behavior was achieved simply by adding acid and base alternately.     

A new stereoselective synthesis of ciguatoxin right wing fragments

The right wings (13 and 14) of ciguatoxins were synthesized highly stereoselectively. Key transformations in the synthesis are (i) an oxiranyl anion strategy to attach the H ring, (ii) intramolecular carbonyl olefination to cyclize the J ring, (iii) regio- and stereoselective reduction of the epoxyacetal to install the C42-stereocenter, and (iv) stereoselective reductive etherification to construct the K ring. The present procedure greatly improved the stereoselectivity and efficiency in comparison to a previous synthesis. Remarkably, only 23 steps were required from monocyclic I ring 5 to construct the ciguatoxin right wings. The high practicality of the present synthesis ensures a sufficient supply of these complex fragments for total syntheses and biomedical applications.     

A versatile synthesis of 2,4-substituted oxazoles

A variety of five-membered ring oxazoles have been synthesised with complete regiocontrol and without the requirement for ring oxidation via a reaction sequence based on a vinyl sulfonamide template.