14-membered Lactone Research Articles

Biotransformation of the mycotoxin, zearalenone, to a non-estrogenic compound by a fungal strain of Clonostachys sp.

Zearalenones are mycotoxins with estrogenic activity consisting of a resorcinol moiety fused to a 14-membered macrocyclic lactone and are produced by various Fusarium species. We found that Clonostachys rosea IFO 7063 was effectively capable of converting zearalenone (1) to cleavage product (2), 1-(3,5-dihydroxyphenyl)-10'-hydroxy-1'E-undecene-6'-one. Moreover, cleavage product 2 did not show potent estrogenic activity like that of 1 and 17beta-estradiol in the human breast cancer MCF-7 cell proliferation assay.

Ring Closing Metathesis Reaction of Dienes with Acrylate Moiety Leading to 5- to 7-Membered Lactones and Cyclization to 14-Membered Rings

Dienes with acrylate moiety have been subjected to olefin metathesis reactions using (PCy 3 ) 2 Cl 2 Ru=CHPh (1) and (PCy3)Cl 2 [H2imid(Mes) 2 ]Ru=CHPh (2). 5- to 7-Membered α,β-unsaturated lactones were obtained in good yields. Formation of 14-membered compounds was attempted using different substrates.

Stereocontrolled synthesis of the diene and triene macrolactones of oximidines I and II: organometallic coupling versus standard macrolactonization.

[structure: see text]. Stereocontrolled construction of the 12-membered diene and triene lactones 1, 2, and 3, characteristic of the antitumor agent oximidines I and II, are reported and were based on an intramolecular Castro-Stephens coupling for the construction of a cyclic enyne or dienyne followed by stereoselective reduction of the cyclic alkyne for introduction of the cis-olefin of the targets. A comparison of the effectiveness of this protocol is made with standard macrolactonization.

Micromonospolides A–C, new macrolides from Micromonospora sp.

Three new macrolides, micromonospolides A–C, have been isolated from a new species of the genus Micromonospora and their structures were elucidated to be bafilomycin-type macrolides which have a 16-membered lactone ring on the basis of spectroscopic data. Micromonospolides A–C inhibited gastrulation of starfish embryos at minimum inhibitory concentrations of 0.010, 0.011 and 1.6 μg mL −1, respectively.

Multiplolides A and B, new antifungal 10-membered lactones from Xylaria multiplex.

Two new 10-membered lactones, namely, multiplolides A (1) and B (2), were isolated from the broth extract of the fungus Xylaria multiplex BCC 1111. Chemical structures of 1 and 2 were elucidated on the basis of their spectral data. Multiplolides A (1) and B (2) exhibited antifungal activity against Candida albicans with IC(50) values of 7 and 2 microg/mL, respectively. Both 1 and 2 were inactive in the screening systems toward the malarial parasite Plasmodium falciparum (at 20 microg/mL) and were not cytotoxic to BC-1 and KB cell lines (at 20 microg/mL).

The stereochemistry of the Nozaki-Hiyama-Kishi reaction and the construction of 10-membered lactones. The enantioselective total synthesis of (-)-decarestrictine D

The use of the intramolecular Nozaki-Hiyama-Kishi reaction to construct 10-membered lactones is described. The influence of the nature of the protecting groups at C4 and C5 on the stereochemistry of the newly formed stereogenic center at C7 was investigated. The utility of this methodology has been demonstrated in the stereoselective total synthesis of (-)-decarestrictine D from 1,3-propanediol and polyhydroxybutyrate (PHB) in 13 steps and 6.3% overall yield.

Micromonospolide A, a new macrolide from Micromonospora sp.

A new macrolide, micromonospolide A, was isolated from an undescribed actinomycete, Micromonospora sp., and its structure was elucidated to be a bafilomycin-type macrolide which has a 16-membered lactone ring on the basis of spectroscopic data. Micromonospolide A inhibited gastrulation of starfish embryos at a concentration of 10 ng/ml or greater.

Methodology Based on Chiral Silanes in the Synthesis of Polypropionate‐Derived Natural Products − Total Synthesis of Epothilone A

Epothilones A and B (1 and 2) are natural products with potent antitumor activity. These compounds have a TaxolTM-like mechanism of action against tumor cells. A total synthesis of epothilone A (1) is reported, which is based on the synthesis and union of two advanced fragments: C3-C11 fragment 4 and C12-C21 fragment 5. Bond construction methodology based on chiral silanes was utilized to introduce the key C6 and C7 stereocenters of fragment 4. A lipase-mediated kinetic resolution established the C15 stereocenter of fragment 5. The 16-membered lactone was constructed using a three-step sequence: an intermolecular B-alkyl Suzuki coupling of 4 and 5, an aldol condensation, and a Yamaguchi-type macrolactonization reaction.

Enantioselective synthesis of a fluorinated analogue of the orsellinic acid-type twelve-membered lactone lasiodiplodin.

The chemoenzymatic synthesis of the racemate and the one enantiomer of the fluorinated analogue 8 of the natural cyclooxygenase inhibitor lasiodiplodin is decribed. A lipase-mediated deracemization of the fluorohydrin 18 provided the chiral, nonracemic building block for the enantioselective synthesis of the title compound. The key step was the formation of the 12-membered lactone by a ring-closing metathesis.

Comparative study of conformational effects on stereoselective lipase catalysed acetylation of sec hydroxy groups in diastereomeric 14-membered lactones and their acyclic analogs

Stereoselective acetylation of sec hydroxy groups in a diastereomeric (1:1) mixture of macrocyclic lactones 14, 15, catalysed by seven microbial lipases in n-heptane afforded the C(7)- O-acetyl derivative 17 with up to 99% diastereomeric excess (d.e.), whereas acetylation of their acyclic analogs 10, 11 afforded C(5)- O-acetyl derivative 13 with up to 93% d.e. Six lipases, from Pseudomonas cepacia (PCL), Pseudomonas fluorescens (PFL), Geotrichum candidum (GCL), Candida cylindracea (CCL) and Pseudomonas cepacia immobilised on ceramics (PS-C) predominantly acetylate cyclic diastereomer (3 S,7 S)- 15 to (3 S,7 S)- 17; only Candida antarctica-B (CAL-B) lipase predominantly acetylates (3 S,7 R)- 14 to (3 S,7 R)- 16. With acyclic analogs 10, 11 the same set of lipases exhibited different diastereoselective bias; CAL-B, GCL and CCL predominantly acylate (1 S,5 S)- 11 to (1 S,5 S)- 13, whereas PCL, PS-C, PFL and PSL acylate predominantly (1 S,5 R)- 10 to (1 S,5 R)- 12. Only GCL exhibited higher stereoselectivity for an acyclic pair of stereoisomers with higher conformational flexibility, over cyclic diastereomeric substrates with a conformationally restricted macrocyclic ring. The preference of PCL for macrocyclic substrates is particularly interesting, in view of the recently suggested binding mode of a series of acyclic sec alcohols in the extended conformation.

Clarithromycin hydrochloride 3.5-hydrate

The absolute configuration was determined for the title compound, C38H70NO13+·Cl−·3.5H2O. The cation contains a 14-membered macrocyclic lactone and two sugars, namely cladinose and desos­amine. The six-membered rings of the sugars adopt chair conformations. The structure is stabilized by strong hydrogen bonds, with O⋯O distances in the range 2.486 (9)–2.830 (5) Å; other distances are N⋯O = 2.860 (5), N⋯Cl = 3.134 (4) and O⋯Cl = 3.303 (4) Å.

Efficient asymmetric synthesis of radicicol dimethyl ether: a novel application of ring-forming olefin metathesis.

A concise, stereospecific synthesis of radicicol dimethyl ether is presented. The strategy relies on a convergent three-stage assembly of the 14-membered lactone which has, as a key transformation, a novel ring-forming metathesis reaction utilizing a vinyl epoxide.

First total synthesis of aspinolide B, a new pentaketide produced by Aspergillus ochraceus.

The first asymmetric total synthesis of Aspinolide B (1), a new 10-membered lactone discovered by chemical screening methods in the cultures of Aspergillus ochraceus, has been accomplished. The key steps included a selective Felkin-type addition of TMS-acetylene to aldehyde 3a and a Nozaki-Hiyama-Kishi coupling reaction to build the required 10-membered ring. This synthesis confirmed the absolute stereochemistry of aspinolide B, established through Helmchen's method and corrected its previously reported specific optical rotation.

Enzymatic synthesis of polyesters from lactones, dicarboxylic acid divinyl esters, and glycols through combination of ring-opening polymerization and polycondensation.

Enzymatic copolymerization of lactones, divinyl esters, and glycols has been performed using lipase as catalyst to produce ester copolymers. The monomers used in this study were 12-, 13-, and 16-membered lactones, divinyl esters of adipic and sebasic acids, and alpha,omega-glycols. Candida antarctica and Pseudomonas cepacia lipases showed relatively high catalytic activity for the present copolymerization, yielding the copolymer having relatively high molecular weight in moderate yields. From 13C NMR analysis, the resulting product was not a mixture of homopolymers, but a copolymer derived from the monomers. NMR data and reaction monitoring results indicate that two different modes of polymerization, ring-opening polymerization and polycondensation, simultaneously take place through enzyme catalysis in one-pot to produce ester copolymers.

Controlled ring-opening polymerization of -pentadecalactone with yttrium isopropoxide as an initiator

The ring-opening polymerization of ω-pentadecalactone (PDL), a 16-membered lactone, in the bulk and in solution using yttrium isopropoxide as an initiator was investigated. All isopropoxide groups of yttrium isopropoxide participated in the initiation and the polymerization took place via acyl-oxygen cleavage of the monomer. The molecular weights of the resulting polymers could be controlled effectively by varying the monomer/initiator ratio. An induction period was observed for the bulk polymerization conducted at 60°C. DSC analyses indicated that poly(ω-pentadecalactone) is a highly crystalline polymer, having a high crystallization rate.

Stereoselectivity of macrocyclic ring-closing olefin metathesis

Macrocyclic ring-closing olefin metathesis using ruthenium catalyst 3 was performed to produce a 14-membered lactone. The E/Z ratio of lactone was high regardless of the R group (auxiliary) or the initial alkene stereochemistry. A kinetic study demonstrates that the high E/Z ratio is due to secondary metathesis reactions that isomerize the product to the thermodynamic E/Z ratio.

Stereoselectivity of macrocyclic ring-closing olefin metathesis.

[reaction: see text] Macrocyclic ring-closing olefin metathesis using ruthenium catalyst 3 was performed to produce a 14-membered lactone. The E/Z ratio of lactone was high regardless of the R group (auxiliary) or the initial alkene stereochemistry. A kinetic study demonstrates that the high E/Z ratio is due to secondary metathesis reactions that isomerize the product to the thermodynamic E/Z ratio.

Apicularen A and B, Cytotoxic 10-Membered Lactones with a Novel Mechanism of Action fromChondromyces Species (Myxobacteria): Isolation, Structure Elucidation, and Biosynthesis

A novel highly cytotoxic metabolite, apicularen A (1), was isolated in a screening of the myxobacterial genus Chondromyces. The structure of 1 is characterized by a salicylic acid residue as part of a 10-membered lactone, which bears an acylenamine side chain. Compound 1 is an inhibitor of the proliferation of human cancer cell lines and induces apoptosis. Apicularen A (1) is present in nearly every strain of C.apiculatus, C. pediculatus, C. lanuginosus and C. robustus. Habitually 1 is accompanied by different amounts of a more polar variant, apicularen B (2), which was identified as 11-O-(2-N-acetamido-2-deoxy-β-D-glucopyranosyl)apicularen. According to feeding experiments with 13C-labeled acetates, glycine, and methionine, apicularen A (1) is an acetate-derived polyketide containing a glycine residue as precursor of the enamine. Uncommonly, the C3 starter unit is not assembled from propionate but from acetate and methionine.

The Application of Transition Metal Catalysis for Selective Cyclocarbonylation Reactions. Synthesis of Lactones and Lactams

A variety of 5-, 6-, and 7-membered ring lactones and lactams have become available via carbonylative cyclization reactions catalyzed by different transition metal complexes. Palladium and rhodium complexes are the most widely used catalysts for the cyclization reactions. Furanones can be synthesized either by the catalytic intermolecular cyclocarbonylation of iodoarenes with alkynes or alkynols, or by intramolecular cyclocarbonylation of alkynols. γ-Butyrolactones are mainly prepared by the intramolecular cyclocarbonylation of allyl alcohol derivatives catalyzed by palladium(0) complexes and 1,4-bis(diphenylphosphino)butane (dppb). The replacement of dppb by a chiral ligand leads to the formation of optically active γ-butyrolactones. Furthermore, 5-, 6-, and 7-membered ring bicyclic and polycyclic lactones and lactams are obtained by the Pd(II) catalyzed intramolecular cyclocarbonylation of 2-allylphenol and 2-allylaniline derivatives in the presence of syngas. The regiochemical control of the reaction depends on the choice of solvent, the nature of the metal and added ligand, and the relative pressures of the gases (CO and H2).

Synthesis of Constitutionally Unsymmetric 7-Membered Biaryl Lactones by Ni-Mediated Intramolecular Coupling

The synthesis of a new constitutionally unsymmetric, configurationally stable (since 7-membered) biaryl lactone is described. Among several `redox-neutral' and reductive coupling methods tested, only the Ni(0)-mediated intramolecular ring closure of suitably substituted dihalogen esters gave 7-membered biaryl lactones.