Aminotenuazonic Acid: Isolation,Structure Elucidation,Total Synthesis and Herbicidal Activity of a New Tetramic Acid from Fruiting Bodies of Laccaria Species

(5S,6S)-Aminotenuazonic acid, a new 3-acyltetramic acid, related to the well-known mycotoxin tenuazonic acid has been isolated from fruiting bodies of Laccaria bicolor. Its structure was mostly established by analysis of its 2D NMR and HR-(+)-ESI-MS spectra. A total synthesis starting from N-Boc-l -isoleucine gave (5S,6S)-aminotenuazonic acid in 8 % yield over nine steps (67 % de). The key steps of the total synthesis are a light-initiated Hofmann–Löffler–Freytag radical chain reaction and a Dieckmann cyclisation. The relative and absolute configurations of the natural product were determined by comparison of its NMR and CD spectra with those of the corresponding enantiopure synthetic compounds. Metabolic profiling of crude extracts of different mushrooms showed that aminotenuazonic acid is present in all four of the investigated Laccaria species. Aminotenuazonic acid shows phytotoxic activities against the root and shoot growth of Lepidium sativum, Pinus sylvestris and Arabidopsis thaliana comparable to those of tenuazonic acid.     

Enzymatic Benzofuranoindoline Formation in the Biosynthesis of the Strained Bridgehead Bicyclic Dipeptide (+)-Azonazine A

We uncovered and reconstituted a concise biosynthetic pathway of the strained dipeptide (+)-azonazine A from marine-derived Aspergillus insulicola. Formation of the hexacyclic benzofuranoindoline ring system from cyclo-(l -Trp-N-methyl-l -Tyr) is catalyzed by a P450 enzyme through an oxidative cyclization. Supplementing the producing strain with various indole-substituted tryptophan derivatives resulted in the generation of a series of azonazine A analogs.     

The Effect of Trifluoroethoxy Groups on the Structures of Eight-Membered Ring-Containing Cyclic Phosphites 1

New phosphites 1–4 were synthesized from phosphorus trichloride and an appropriate diphenol followed by the addition of trifluoroethanol in the presence of triethylamine. These phosphites are to serve as precursors in the syntheses of biorelated hypervalent phosphoranes. ¹H, ¹⁹F, and ³¹P NMR spectra were recorded. X-ray analysis of 3 and 4 revealed that the sulfur-containing eight-membered ring was in a syn conformation that a allowed a sulfur donor interaction to the phosphorus atom, whereas for phosphite 2, the eight membered sulfonyl containing ring was in an anti conformation that did not allow a donor interaction to phosphorus from the oxygen atom of the sulfonyl group. Structural comparisons are made with related cyclic phosphites and phosphates having donor atoms in eight-membered rings.     

Experimental and theoretical conformation analysis of eight-membered silocines with planar fragments

The dipole moments of 6-thia-4,5: 6,7-dibenzo-1,3,2-dioxasilocines were determined experimentally and calculated at the DFT B3LYP/6-31G* level of theory and by the additivity scheme. The experimental and theoretical (DFT B3LYP/6-31G*) conformation analysis of eight-membered 1,3,2-dioxasilocines having planar fragments showed that these compounds in solution exist as boat-chair, boat-boat, or twist-boat conformers, depending on the presence of unsaturated planar fragment, nature of the heteroatom in position 6 of the eight-membered ring, and substituents on the silicon atom.     

New Terpenoids from Basidiomycetes Russula lepida

Three new triterpenoids and two new aristolane sesquiterpenoids, namely (24E)‐3β‐hydroxycucurbita‐5,24‐diene‐26‐oic acid ( 1 ), (24E)‐3,4‐secocucurbita‐4,24‐diene‐3,26‐dioic acid ( 4 ), (24E)‐3,4‐secocucurbita‐4,24‐diene‐3,26,29‐trioic acid ( 5 ), rulepidadiol ( 6 ), and rulepidatriol ( 7 ), were isolated from the fruiting bodies of Basidiomycetes Russula lepida. Their structures were established by spectral methods. Acids 4 , and 5 are the first examples of naturally occurring seco‐ring‐A cucurbitane triterpenoids. Alcohols 6 and 7 , belonging to the aristolane‐type sesquiterpenoids, are of a type rather rare in nature, especially among fungal species.     

A density functional theory study of interaction between formamide and guanine

Hydrogen bonding in complexes formed between formamide and guanine molecules was completely investigated using density functional theory (DFT) at the 6-311++G(d, p) level. For comparison, the HF and MP2 methods were also used. Nine stable cyclic structures stabilized by two hydrogen bonds were found. One of these was a six-membered ring, five were seven-membered rings, and the others were eight-membered rings. The eight-membered ring is preferable to the seven-and six-membered ones as follows from H-bond lengths and interaction energies. The FG4 structure was calculated to be the most stable, and another cyclic structure, FG5, was least stable because of the six-membered ring and the weakest interaction. The infrared spectrum frequencies, intensities, and vibrational frequency shifts are also reported. The text was submitted by the authors in English.     

5,6,7,8-Tetrahydro-4H-1,2,5-oxadiazocin-6-one durch Ringerweiterung nach Addition eines 3-Isoxazolidinons mit 3-Amino-2H-azirinen

5,6,7,8-Tetrahydro-4H-1,2,5-oxadiazocin-6-ones, Ring Enlargement Products from a 3-Isoxazolidinone and 3-Amino-2H-azirines 3-Dimethylamino-2H-azirines 1 and 4,4-dimethyl-3-isoxazolidinone ( 7 ) undergo already at room temperature a ring enlargement reaction to yield 5,6,7,8-tetrahydro-4H-1,2,5-oxadiazocines of type 8 . The structure of 8a has been confirmed by X-ray crystallography. The conformation of the eight-membered ring with a trans-amide group is of particular interest (Fig. 1 and 2).     

An Efficient Total Synthesis of (2E,4E,7R)-Farnesa-2,4,10-triene from (R)-(+)-Citronellal

(2E,4E,7R)-farnesa-2,4,10-triene(Caparratriene) ( 1 ), a novel sesquiterpene hydrocarbon with significant growth inhibitory activity against CEM leukemia cells, was first synthesized from (R)-(+)-citronellal ( 2 ) by employing titanium-induced intermolecular carbonyl-coupling as the key step. The absolute configuration of (+)-Caparratriene was determined to be 7R.     

A novel glyceryl ester (glyceryl dendryphiellate A), a trinor-eremophilane (dendryphiellin A1), and eremophilanes (dendryphiellin E1 and E2) from the marine deuteromycete Dendryphiella salina (SUTHERLAND) PUGH et NICOT

Continuing studies of the global extracts from cultures of the marine deuteromycete Dendryphiella salina have led to the isolation of novel compounds that add to the scarce list of marine fungal metabolites. Besides (22E)-ergosta-4.6,8(14),22-tetraen-3-one which, though known from basidiomycetes, was unknown in the sea, they are an unusual glyceryl ester, i.e. glycer-1-yl dendryphiellale A (= (+)-(2R)-2,3-dihydroxyprop-l-yl (6S,2E,4E)6-methylocta-2,4-dienoate; (+)- 1 ), a trinor-eremophilane, i.e. dendryphiellin A1 ( = (+)-(3R*,4E,6E)-7-{[(1R*,2S*,7R*,8aR*)-1,2,6,7,8,8a-hexahydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2yl]oxycarbonyl}-3-methylhepta-4,6-dienoic acid; (+)- 11 ), and two eremophilanes, i.e. dendryphiellin El ( = (+)-(1R*, 2S*, 7S*,8aR*)-1,2,6,7,8,8a-hexahydro-1,8a-dimethyl-7-(1-methylethenyl)-6-oxonaphthalen-2-yl(6S,2E,4E)-6-methyl-octa-2,4-dienoate; (+)- 13 ) and dendryphiellin E2 ( = (+)-(1R*, 2S*, 8aR*)-1,2,6,7,8,8a-hexahydro-7-isopropyl-idene-1,8a-dimethyl-6-oxonaphthalen-2-yl (6S,2E,4E)-6-Methylocta-2,4-dienoate; (+)- 14 ). Absolute configurations have been established for (+)- 1 via total synthesis and for the acid portion of (+)- 13 and (+)- 14 via transesterification in NaOMe/MeOH which gave in both cases melhyl dendryphiellate A ((+)- 16 ) of known configuration and the free alcoholic moiety of (+)- 14 , i.e. (+)- 17 .     

Synthesis of the Bretonins,Polyolefinic Esterified Glyceryl Ethers of an Unidentified Sponge from the North-Brittany Sea: Absolute Configuration and Novel Structure Assignment

The absolute configurations of acetylated bretonin A (= (+}-( R )-1-[(acetoxy)methyl]-2-{[(4E,6E,8E)-dodeca-4,6,8-trienyl]oxy}ethyl 4-acetoxybenzoate; (?)- 1b ) and isobretonin A (= (+)-(S)-3-{[(4E,6E,8E)-do-deca-4,6,8-trienyl]oxy}-2-hydroxypropyl 4-hydroxybenzoate; (+)-2), previously isolated from an undetermined sponge of the North Brittany sea, were established by comparison with synthetic (+)- lb and (+)- 2 , obtained from the condensation of commerical (?)-(R)-2,2-dimethyl-1,3-dioxolan-4-yl p-toluenesuifonate ((?)-(R)- 15 ) with a mixture of (4E,6E,8E)- ( 14e ) and (4E,6Z,8E)-dodeca-4,6,8-trien-1-ol ( 14z ). This also allowed confirming the structure and configuration of bretonin B (= (S)-2-{[(4E,6Z,8E)-dodeca-4,6,8-trienyl]oxy}-1-(hydroxy-methyl)ethyl 4-hydroxybenzoate; 3 ) which was also isolated from the same sponge, albeit in a too small amount for a complete study. As concerns the glyceryl ethers precursors of the bretonins, co-occurrence of the usual (S)-con-figuration (from 1a ) with the unusual (R)-configuration (from (+)- 2 )) poses intriguing biogenetic problems.     

Ring-Enlargement and Ring-Opening Reactions of 1,2-Thiazetidin-3-one 1,1-Dioxides with Ammonia and Primary Amines as Nucleophiles

The N-benzyl- and N-alkyl-substituted 1,2-thiazetidin-3-one 1,1-dioxides 1b – d reacted readily with NH₃ and primary amines via ring opening. The reaction with NH₃ proceeded at −78°→room temperature yielding ring-opened adducts via nucleophilic attack of NH₃ at the sulfonyl group, whereas the reactions with amines at room temperature yielded products via attack at the carbonyl group. The N-unsubstituted analogue 1a , when reacted with benzylamine in refluxing EtOH, also gave a product of ring opening via nucleophilic attack at the carbonyl group of 1a . The transamidation-like reactions of the 2-(aminoalkyl)-1,2-thiazetidin-3-one 1,1-dioxides 19a – d proceeded via six-, seven-, and eight-membered intermediates, giving the ring-enlarged eight-, nine-, and ten-membered products 21 – 24 (Schemes 8 and 9), respectively, in 42 – 87% yields. The products resulted from the nucleophilic attack of the amino group of the side chain at the carbonyl C-atom. The structure of the eight-membered product 24 with an asymmetrically situated methyl substituent was established by X-ray crystallography.     

Asymmetric approach towards the total synthesis of (+)-actinopyllic acid

This paper describes our efforts towards the asymmetric total synthesis of (+)-actinophyllic acid. Starting from the chiral oxazolidinone 9, an azocino [4,3-b]indolyl intermediate (5) possessing the A/B/C ring system and the C16 quaternary stereogenic center of actinophyllic acid has been synthesized. Key steps include a LHMDS-promoted condensation to establish the critical C2–C16 bond and a successive four-step transformation to assemble the eight-membered C-ring of the target molecule.     

Dendryphiellin A,the First Fungal Trinor-eremophilane. Isolation from the marine deuteromycete Dendryphiella salina (SUTHERLAND) PUGHet NICOT

The novel metabolite dendryphiellin A ( = (+)-(1R,2S,8aR)- 1,2,6,7,8,8a-hexahydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2-yl (6R*, 2E,4E)-8-hydroxy-6-methylocta-2,4-dienoate; (+)- 1 ) is isolated from cultures of the marine deuteromycete Dendryphiella salina. There is no precedent in fungi for trinor-eremophilanes or for branched C₉ carboxylic acids, the two classes of compounds constituting (+)-1. The structure is secured by NMR spectroscopy and hydrolysis of (+)-1 to give the side-chain moiety ((6R*,2E,4E)-8-hydroxy-6-methylocta-2,4-dienoic acid ( 2 )) intact, whilst the trinor-ermophilane moiety is decomposed. The absolute configuration at the trinor-eremophilane moiety is established from exciton coupling between the dienone and the diene-ester functions.     

Novel Trinor-eremophilanes (Dendryphiellin B,C, and D), Eremophilanes (Dendryphiellin E,F, and G), and Branched C9-Carboxylic Acids (Dendryphiellic Acid A and B) from the Marine Deuteromycete Dendryphiella salina (SUTHERLAND) PUGHet NICOT

Further investigation of global extracts from cultures of the marine deuteromycete Dendryphiella salina leads to the isolation of three novel trinor-eremophilanes esterified by branched C₉-carboxylic acids, dendryphiellin B (= (+)-(1R*,2S*,7R*,8aR*)-1,2,6,7,8,8a-hexahydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2-yl (6R*, 2E, 4E)-6-hydroxy-6-methylocta-2,4-dienoate; (+)- 2 ), dendryphiellin C (=(+)-(1R*, 2S*, 7R*, 8aR*)-1,2,6,7,8,8a-hexa-hydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2-yl (6S, 2E, 4E)-6-methylocta-2,4-dienoate; (+)- 3 )), and dendryphiellin D (=(+)-(1R*, 2S*, 7R*, 8aR*)-1,2,6,7(8,8a-hexahydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2-yl (6R*,2E,4E)-6-(hydroxymethyl)octa-2,4-dienoate; (+)- 4 ). An intact eremophilane, dendryphiellin E ( 5 ), and its ethanolysis product dendryphiellin F whose absolute configuration is represented by structural formula (+)- 6 are also isolated from the above extracts. Dendryphiellin E exists as an open form 5a in equilibrium with a closed form 5b . A similar equilibrium exists between the open form 8a and the closed form 8b of a non-esterified eremophilane, dendryphiellin G ( 8 ), which is isolated too from the above extracts and proves structurally related to the cyclic portion of 5 . Finally, the free, branched C₉-carboxylic acids dendryphiellic acid A ((+)- 9 ) and B ((+)- 10 ) which correspond to side chains of the above esterified terpenes are also isolated from the above extracts.     

Thiol-dependent serine alkaline proteases from Bacillus sp. HR-08 and KR-8102

Two Bacillus sp. strains, HR-08 and KR-8102, isolated from soil of the west and north parts of Iran were screened on gelatin agar medium for their ability to produce alkaline protease. The enzymes were active in a wide pH range (6.0–11.0) and stable in the alkaline range (7.0–12.0). The optimum temperatures for the protease from HR-08 and KR-8102 were 65 and 50°C, respectively. The irreversible thermoinactivation of HR-08 and KR-8102 proteases showed that the stability of HR-08 enzyme was higher than that of KR-8102 and the half-lives of these enzymes were 95 and 32 min at 50°C, respectively. In the presence of 10 mM Ca²⁺, HR-08 retained 100, 90, and 20% of its initial activity after heating for 30 min at 50, 60, and 70°C, respectively. Enzymes were inhibited by phenylmethylsulfonyl fluoride and iodoacetate. After inhibition by iodoacetate, both enzymes were reactivated by dithiothreitol. These data show that the enzymes seem to be thiol-dependent serine alkaline proteases. The enzymes especially from HR-08 were stable in the presence of H₂O₂, surfactants, and local detergents; their activities were enhanced in the presence of 5 mM Fe²⁺; and the presence of 5mM metal ions such as Mg²⁺, Cu²⁺, and Mn²⁺ produced almost no effect.     

The crystal structure of a tricarbonyliron-substituted cyclobutadiene complex: Tricarbonyl[1,2,2a,12a-η-5,10-dimethyldibenzo[a,c]cyclobuta[f]cyclooctene-3,12-dione] iron

The crystal structure of tricarbonyl[1,2,2a,12a-η-5,10-dimethyldibenzo[a,c] cyclobuta[f] cyclooctene-3,12-dione] iron, C₂₀O₂H₁₄Fe(CO)₃, has been determined by the single crystal X-ray diffraction technique using data collected with a fully automated diffractometer. The unit cell is monoclinic, space group P2₁/c with a = 12.025(2), b = 23.204(3), c = 14.614(2) Å, β = 102.16(2)°, and contains eight molecules (two per asymmetric unit). The structure was elucidated to study the coordination of the iron atom and to correlate the conformation of the eight-membered ring with an NMR study. The final structure was obtained by Patterson-superposition and Fourier techniques and refined by full-matrix least-squares to a crystallographic residual of 0.070. In both independent molecules the iron atom is 1.77 Å from the cyclobutadiene ring to which it is coordinated. The eight-membered ring is flattened from a boat conformation and the six-membered rings are twisted from coplanarity by an angle of 74°. The twist is such that if one ring points above the eight-membered ring, the other ring will point below it with concomitant pointing in the opposite sense by neighboring carbonyl groups. Such a structure has conformational chirality. It is postulated that the stability of each enantiometer is due to the particularly high energy of the transition state through which each would pass to achieve inter-conversion.     

Synthesis and properties of (E)-1,2-difluoroethylene derivatives: improvement of the ultraviolet light stability

The synthesis and properties of (E)-α,β-difluorostilbene derivatives were studied. In particular, we investigated three suppression methods of (E)–(Z) isomerisation by shortening the molecular conjugation length, which included the introduction of a fluorine atom into the ortho or para position of the benzene ring or the replacement of the benzene ring with a cyclohexane ring. The relationship between the molecular structure of liquid crystals and the level of isomerisation by ultraviolet (UV) light was discussed.     

Total Synthesis of (−)-Pepluanol B: Conformational Control of the Eight-Membered-Ring System

The first total synthesis of the Euphorbia diterpenoid pepluanol B in both racemic and enantioenriched form involves 20 steps from a known bicyclic diol. This synthesis features an unprecedented bromo-epoxidation to control the eight-membered-ring conformation. In addition, salient reactions for the construction of the tetracyclic backbone include a sterically challenging aldol reaction to establish the quaternary center, a ring closing metathesis (RCM) to forge the eight-membered ring, and a diastereoselective cyclopropanation to assemble the embedded cyclopropane motif.     

Synthese des Dysidins

Synthesis of Dysidin The synthesis of dysidin ((?)- 1 ), the enantiomer of a metabolite of the marine sponge Dysidea herbacea, is described. To effect the synthesis, (±)-5-isopropyl-4-methoxy-3-pyrrolin-2-one ( 7 ) is converted to its lithium salt and reacted with (?)-(5R,2E)-3-methoxy-5-trichloromethyl-2-hexenoyl chloride ((-)- 11 ) to give (?)- 1 and its diastereoisomer (+)-5-epidysidin ((+)- 12 ) epimeric at C(5) of the pyrrolinone ring. The (?)-acyl chloride (?)- 11 has been synthesized from (+)-(R)-3-(trichloromethyl)butanoic acid ((+)- 8 ) via the intermediates (+)- 9 and (?)- 10 , the pyrrolinone 7 from N-benzyl-oxycarbonyl-L-valine via the intermediate 5 . The enantiomers of acid 8 have been resolved by fractional crystallization of their diastereoisomeric N-(1-phenylethyl)amides. The (R)-chirality of (+)- 8 was determined by comparing the ¹H-NMR spectra of the diastereoisomeric N-(1-phenylethyl)amides 16 and 17 , made from (+)- 8 by substituting deuterium for chlorine, with the spectra of the N-(1-phenylethyl)amides 14 and 15 of known absolute configuration. This correlation shows that literature value (R) for (?)- 8 is in error. Therefore, the structural formulae of (?)-dysidenin and (+)-isodysidenin, two other metabolites of D.herbacea, have to be changed to their mirror images as shown in formulae (?)- 3 and (+)- 4 , respectively.     

New Diarylheptanoids and Kavalactone from Alpinia katsumadai Hayata

Two new diarylheptanoids, katsumains A ( 1 ) and B ( 2 ), and one new kavalactone, katsumadain ( 3 ), together with the three known compounds (4E,6E)‐1,7‐diphenylhepta‐4,6‐dien‐3‐one ( 4 ), (5R,6E)‐1,7‐diphenyl‐5‐hydroxyhept‐6‐en‐3‐one ( 5 ), and cardamonin ( 6 ), were isolated from the seeds of Alpinia katsumadai Hayata . Their structures were elucidated mainly by spectroscopic methods (1D‐ and 2D‐NMR) and by mass spectrometry (HR‐ESI‐MS). Besides, the erroneous nomenclatures for (+)‐linderatin and (+)‐neolinderatin as given in [10] [11] were corrected to be 2′,4′,6′‐trihydroxy‐3′‐[(3R,4R)‐4‐isopropyl‐1‐methylcyclohex‐1‐en‐3‐yl]dihydrochalcone for (+)‐linderatin and 2′,4′,6′‐trihydroxy‐3′,5′‐bis[(3R,4R)‐4‐isopropyl‐1‐methylcyclohex‐1‐en‐3‐yl]dihydrochalcone for (+)‐neolinderatin, respectively.