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An enantioselective total synthesis of spliceostatin E has been accomplished. The δ-lactone unit A was constructed from readily available (R)-glycidyl alcohol using a ring-closing olefin metathesis as the key reaction. A cross-metathesis of ring A containing δ-lactone and the functionalized tetrahydropyran B-ring provided spliceostatin E. Our biological evaluation of synthetic spliceostatin E revealed that it does not inhibit splicing in vitro and does not impact speckle morphology in cells. Spliceostatin E was reported to possess potent antitumor activity.

A concise synthesis of homocitric acid lactone was developed to accommodate systematic placement of carbon isotopes (specifically (13)C) for detailed studies of this cofactor. This new route uses a chiral allylic alcohol, available in multigram quantities from enzymatic resolution, as a starting material, which transposes asymmetry through an Ireland-Claisen rearrangement.

An unprecedented N-heterocyclic carbene-catalyzed annulation of isatin-derived enals and o-hydroxyphenyl-substituted p-quinone methides as bifunctional reagents has been discovered. The new protocol involves a 1,6-addition of the homoenolate equivalent intermediates to the hydroxy donor-1,6-Michael acceptors and leads to spirocyclic oxindole-ε-lactones in high yields and very good stereoselectivities. [ABSTRACT FROM AUTHOR]

Enantioselective synthesis of tricyclic δ-lactones with three contiguous stereocenters has been demonstrated by the N-heterocyclic carbene (NHC)-catalyzed functionalization of benzylic C(sp³)-H bonds. The NHC-catalyzed reaction of enals with dinitrotoluene derivatives under oxidative conditions proceeds via the chiral α,β-unsaturated acylazoliums and produces the δ-lactones in good yields and excellent diastereoselectivity and enantioselectivity. This mild and atom-economic cascade reaction takes place in a Michael/Michael/lactonization sequence and tolerates a broad range of functional groups. [ABSTRACT FROM AUTHOR]

Two novel schinortriterpenoids (SNTs), schincalactones A (1) and B (2), featuring a unique 5/5/6/11/3 ring system, together with schincalide B (3), were isolated from Schisandra incarnata. Their structures were elucidated by detailed spectroscopic analysis, and the absolute configurations of 1 and 3 were confirmed by single-crystal X-ray diffraction. Compounds 1 and 2 possess a 13-membered carbon ring and are the first examples in the SNT family. Plausible biosynthetic pathways of 1-3 were postulated. [ABSTRACT FROM AUTHOR]

Acaulin A (1) and its macrolactone ring-opened congener acaulin B (2) were characterized from the culture of Acaulium sp. H-JQSF (an isopod-associated fungus) as architecturally undescribed trimeric macrodiolides, with the former being antiosteoporotic at 0.4 µM in the prednisolone-induced osteoporotic zebrafish. Identification of acaudiolic acid (3) as the monomeric macrodiolide precursor facilitated the proposal of the acaulin biosynthetic pathway. [ABSTRACT FROM AUTHOR]

A decarboxylative formal [4 + 2] cycloaddition reaction between ethynyl benzoxazinanones and 5-substituted 2-silyloxyfurans catalyzed by chiral Cu–Pybox complex is described. This method allows the formation of intriguing tetrahydroquinolines fused with a butyrolactone moiety featuring three contiguous chiral centers in high yields with excellent diastereo- and enantioselectivities in most cases. The utility of this method was exemplified by the removal of the N-protecting groups and derivatization on the terminal alkyne functionality of the cyclization products. [ABSTRACT FROM AUTHOR]

An Fe(III)-catalyzed hydroallylation of unactivated alkenes with Morita-Baylis-Hillman adducts via an Fe-catalyzed process is described. A variety of alkenes, including mono-, di-, and trisubstituted alkenes, could all smoothly convert to structural diversified cinnamates in this protocol. Interestingly, when the hydroxyl-containing alkenes were used, various lactones could be rapidly assembled. Moreover, this protocol could be applied to late-stage functionalization of natural products. [ABSTRACT FROM AUTHOR]

A practical, electrochemical method is developed for the direct dehydrogenative lactonization of C(sp²/sp³)-H bonds under external oxidant- and metal-free conditions, delivering diverse lactones, including coumarin derivatives with excellent regioselectivity. The scalable nature of this newly developed electrochemical process was demonstrated on a 40 g scale following an operationally simple protocol. The remote lactonization of C(sp³)-H bonds would constitute an important synthetic advance toward electrochemical C-O bond formation. [ABSTRACT FROM AUTHOR]

A synthesis of the core framework of presporolide, which possesses both a strained bicyclo[7.3.0]dodecadiyne moiety and a distinctive macrolactone structure, is reported. This synthesis features: (i) a Cu-mediated O-arylation of a hindered tertiary alcohol using triarylbismuth reagent; (ii) stereoselective construction of the strained nine-membered diyne ring; and (iii) atroposelective formation of the macrolactone. [ABSTRACT FROM AUTHOR]

The umpolung of β,γ-unsaturated diketones through N-heterocyclic carbene catalysis is described, which allows access to a variety of highly functionalized bicyclic cyclohexene-β-lactones and 1,3,4-triaryl benzenes. An unprecedented reaction pattern involving the catalytic formation of nucleophilic O-acylated homoenolate intermediate is proposed. A diverse set of transformations on the product further showed the synthetic potential of this protocol. [ABSTRACT FROM AUTHOR]

A mild photocatalytic manifold for the synthesis of γ-lactones has been developed. Utilizing Ru(bpy)3Cl2 as the photocatalyst, a cheap and reproducible synthetic protocol for γ-lactones has been introduced. Mechanistic studies revealed the successful monitoring of photocatalytic reactions and radical intermediates via high-resolution mass spectrometry. [ABSTRACT FROM AUTHOR]

In this report, the originally proposed rupestonic acid (5) and pechueloic acid (3) were efficiently synthesized. The chiral lactone 13, recycled from the degradation of saponin glycosides, was utilized to prepare the key chiral fragment 11. During the exploration of this convergent assembly strategy, the ring-closing metathesis (RCM), SmI2-prompted intermolecular addition, and [2,3]-Wittig rearrangement proved to be effective transformations for the synthesis of subunits. [ABSTRACT FROM AUTHOR]

A scalable and efficient electrocatalytic dehydrogenative esterification is reported. With an indirect electrolysis strategy, both intra- and intermolecular-type reactions were amenable to this practical method. With n-Bu4NI as the catalyst, undesired decarboxylation and Baeyer-Villiger oxidation were suppressed. More importantly, this novel method provided reliable and direct access to the natural product cytosporanone A on a gram scale. [ABSTRACT FROM AUTHOR]

An N-heterocyclic carbene-catalyzed formal [5 + 5] reaction between enals and furanones that generates multisubstituted coumarins in a single step is reported. Five atoms in each of the substrates are involved in this catalytic process to form a benzene and a lactone ring. The power of the method is further demonstrated in metal-free total syntheses of several natural products (defucogilvocarcins M, E, and V) bearing coumarin as the key structural motif. [ABSTRACT FROM AUTHOR]

Illisimonin A, an unprecedented sesquiterpenoid with a tricyclo[5.2.1.01,6]decane skeleton, was isolated from the fruits of Illicium simonsii. The structure and absolute configuration of 1 were determined using extensive spectroscopic evidence and electronic circular dichroism (ECD) calculations. It was determined that 1 possesses a caged 2-oxatricyclo[3,3,0,14,7]nonane ring system fused to a five-membered carbocyclic ring and a five-membered lactone ring. A plausible biogenetic pathway for 1 was proposed, and 1 showed neuroprotective effects against oxygen-glucose deprivation (OGD)-induced cell injury in SH-SY5Y cells with an EC50 value of 27.72 μM. [ABSTRACT FROM AUTHOR]

An efficient photoredox-catalyzed alkylation/lactonization reaction of unsaturated carboxylic acids by using alkyl N-hydroxyphthalimide esters as alkylation reagents has been developed. Varieties of redox-active esters derived from aliphatic carboxylic acids were proved viable in this method, affording alkyl substituted lactones in moderate to good yields. This redox-neutral procedure features mild conditions and operational simplicity, which provides a new strategy for the synthesis of alkyl substituted lactones. [ABSTRACT FROM AUTHOR]

An efficient gold-catalyzed ring-expansion reaction of enyne-lactones to form 2-oxoninonium intermediates is reported. The 2-oxoninonium generated in this work could undergo further 6p electrocyclization and aromatization reaction to produce different aromatic compounds. [ABSTRACT FROM AUTHOR]

An unprecedented strategy for the highly effective synthesis of γ-lactones from homoallylic alcohols was achieved by palladium catalysis in one step. The protocol affords aryl, alkyl, and spiro γ-lactones directly from readily available homoallylic alcohols in good yields with excellent functional group tolerance and high chemoselectivity under mild conditions. [ABSTRACT FROM AUTHOR]

The total synthesis of biselide E, a marine polyketide isolated from the Okinawan ascidian, has been accomplished. The highlight of this approach is the use of the β-elimination reaction of the chloroacetoxy group for the construction of an unstable six-membered α,β,γ,δ-unsaturated lactone portion at the late stage of the total synthesis. [ABSTRACT FROM AUTHOR]

A robust and scalable route to the taccalonolide skeleton starting from trans-androsterone is presented. The synthesis features a cyclic hydroboration carbonylation reaction, which effectively establishes the trans-hydrindane DE ring junction in a remarkable annulation reaction, as well as a Claisen rearrangement and a catalytic Ullmann-type cyclization. This work is part of a larger effort to uncover new clinical candidates from the taccalonolide class of anticancer agents through advances in chemical synthesis. [ABSTRACT FROM AUTHOR]

The Passerini reaction is a classical and well-known multicomponent reaction for accessing α-acyloxy amides. A single reactant replacement (SRR) approach of Passerini reaction is described, which involves aldehydes, carboxylic acids, and ynamides to constitute a one-pot synthesis of β-acyloxy amides in a convergent manner. When this method was subject to intramolecular reaction, the process would produce phthalide products. The scalability was demonstrated, and a crossover reaction was conducted to elucidate a plausible mechanism. [ABSTRACT FROM AUTHOR]

A highly efficient Cu(I)-catalyzed addition/annulation sequence has been developed for the synthesis of (Z)-ylidenebutenolides employing readily available α-ketoacids and alkynes as substrates. The reactions employ a simple commercially available Cu(I)-catalyst, display good substrate scope, and deliver products with high stereoselectivity. The synthetic utility of the method is demonstrated by the straightforward derivatization of the ylidenebutenolides into a diverse range of heterocycles, and also by the preparation of the natural product bovolide, and analogs thereof. [ABSTRACT FROM AUTHOR]

An unprecedented asymmetric Diels-Alder reaction of 3-hydroxy-2-pyrones with prochiral cyclopentene-1,3-diones via desymmetrization was efficiently realized with high stereoselective control with the aid of fine-tunable cinchona alkaloid derived bifunctional amine-thiourea catalysts bearing multiple hydrogen-bonding donors. This protocol provides an expedient access to the multifunctional-bridged tricyclic lactones featuring four contiguous stereogenic centers and one remote quaternary stereogenic center with a broad substrate scope. The cycloadduct can be readily elaborated into enantioenriched cyclopentane-1,3-diones via ring opening/aromatization. [ABSTRACT FROM AUTHOR]

A one-step preparation of 3,4-disubstituted β-lactones through Rh-catalyzed conjugate addition of aryl or alkenyl boronic acids to α-methylene-β-lactones is described. The operationally simple, stereoselective transformation provides a broad range of β-lactones from individual α-methylene-β-lactone templates. This methodology allowed for a direct, final-step C-3 diversification of nocardiolactone, an antimicrobial natural product. [ABSTRACT FROM AUTHOR]

A Rh(III)-catalyzed C-H activation/cyclization of benzamides and diazonaphthalen-2(1H)-ones for synthesis of lactones has been developed. In the presence of Rh(III) catalysis, the benzamides would form rhodacycle species and could be trapped by diazonaphthalen-2(1H)-ones for arylation, and the following intramolecular lactonization would rapidly furnish the products. Thus, the diazonaphthalen-2(1H)-ones were first revealed as a lactonization component in Rh(III)-catalysis, while the kinetic isotope effect study was conducted and a plausible reaction mechanism was proposed. [ABSTRACT FROM AUTHOR]

Heating a 2,5-furanocyclic (2-azidoethyl)allene initiates a cascade reaction comprising azide-allene cycloaddition, loss of nitrogen, and azatrimethylenemethane (ATMM) diyl-furan transannular (4 + 3)-cycloaddition. The major product of this reaction contains the pentacyclic core common to guanacastepenes D and H and radianspenes J-L; in addition, the central oxa-bridged cycloheptene ring, flanked by two carbocyclic rings, is structurally related to the ABC-ring system found in the cortistatins. This is the first reported synthetic application of a "free" (nonconjugated) ATMM. The cyclization precursors were prepared via the first reported examples of the Ireland-Claisen rearrangement of an ethynyl lactone. [ABSTRACT FROM AUTHOR]

A Pd-catalyzed ring-opening of β-lactones with various types of amines (primary, secondary, and aryl) to provide β-hydroxy amides with excellent selectivity toward acyl C-O bond cleavage is reported. The utility of this protocol is demonstrated in an asymmetric kinetic resolution providing enantioenriched α-methylene-β-lactones. [ABSTRACT FROM AUTHOR]

The first asymmetric total syntheses of scholarisine K and alstolactine A have been accomplished. Our syntheses feature (1) ring closure metathesis and an intramolecular Heck reaction to construct the 1,3-bridged [3,3,1] bicycle (C-D ring), (2) intramolecular alkylation followed by Fischer indolization to form the basic skeleton of akuammilines, and (3) bioinspired, acid-promoted epoxide opening/lactonization to generate the second lactone ring of alstolactine A. These results provide evidence of a biogenetic relationship between scholarisine K and alstolactine A, which should facilitate the preparation of other akuammiline-type natural products and their derivatives for functional studies. [ABSTRACT FROM AUTHOR]

An asymmetric synthesis of the C11-homoterpenoid (+)-Greek tobacco lactone is developed starting from readily available (R)-linalool. The synthesis is comprised of four operations and features a diastereoablative epoxidation and an oxidative tetrahydropyran formation using vanadium-, palladium-, and selenium-catalyzed cyclizations. [ABSTRACT FROM AUTHOR]

Theonellapeptolide Id is a tridecapeptide containing a 37-membered lactone, originally isolated from the marine sponge Theonella swinhoei. In addition to moderate cytotoxicity, immunosuppressive activity had been reported for this natural cyclodepsipeptide. However, the synthetic material to verify its unique biological activity has not been available thus far. In this study, the first total synthesis of theonellapeptolide Id has been performed by solid phase peptide synthesis, and the biological activity has been confirmed in comparison with cyclosporin A. [ABSTRACT FROM AUTHOR]

The first synthesis of cephalimysins B and C is reported. The route features a Ni(II)-diamine-catalyzed enantioselective conjugate addition of a densely substituted 3(2H)-furanone and an efficient dihydroxylation-lactonization sequence as key steps in the assembly of the spirocyclic core. The fully synthetic strategy is amenable to analog preparation. [ABSTRACT FROM AUTHOR]

An NHC-catalyzed enantioselective annulation reaction of enals with an activated ketone is disclosed. The approach proceeds from a formal [3 + 2] annulation of homoenolate with activated ketone and a subsequent ring expansion of γ-lactone by the nitrogen atom of indole. This strategy features a broad substrate scope, affording the corresponding DHPIs in moderate to good yields and with excellent levels of enantioselectivities. Controlled experiments have been conducted to elucidate a plausible mechanism.

γ- and δ-lactones are valuable flavor and fragrance compounds. Their synthesis depends on the availability of suitable hydroxy fatty acid precursors. Three short unspecific peroxygenases were identified that selectively hydroxylate the C4 and C5 positions of C8-C12 fatty acids to yield after lactonization the corresponding γ- and δ-lactones. A preference for C4 over C5 hydroxylation gave γ-lactones as the major products. Overoxidation of the hydroxy fatty acids was addressed via the reduction of the resulting oxo acids using an alcohol dehydrogenase in a bienzymatic cascade reaction.

The racemic total synthesis of asperaculin A, a sesquiterpenoid lactone with an unprecedented structure, has been accomplished in 17 steps from 3-methyl-2-cyclopentenone. Key features of the synthesis are the construction of a central all-carbon quaternary center using the Johnson-Claisen rearrangement, stereocontrolled introduction of a cyano group, and acid-mediated γ-lactonization.