Die Epoxysulfoncyclofragmentierung,eine neue Ringerweiterungsmethode. Synthese von rac.-Muskon

A new ring expansion method using the cyclofragmentation of epoxysulfones; a synthesis of rac. muscone. Starting from the readily available cyclododecanone 1 the hydroxy sulfone 5 has been prepared using standard procedures. Subsequent dehydration followed by an acidic equilibration resulted in a mixture of two endocyclic olefines, from which the olefin 7 showing the (E)-configuration could be isolated by fractional crystallization. Oxidation of 7 produced the epoxy sulfones 8 and 9 . The epoxy sulfone 8 was cyclized to the hydroxy sulfone 10 without any detectable amount of the corresponding epimer 11 . Fragmentation of the intermediate 10 using KOTB produced pure (E)-4-muscenone 12 . The epoxy sulfone 9 was cyclized to a mixture of the two epimeric hydroxy sulfones 14 and 15 . Fragmentation of the two crystalline hydroxy sulfones 14 or 15 with KOTB produced a mixture of 12 and 16 . The ‘one-pot’ preparation of (E)-4-muscenone 12 starting from 8 could also be accomplished. The configurational assignements within this serie are based upon the data of an X-ray analysis of the hydroxy sulfone 10 .     

Oxygenated fatty acids of the seeds ofElaeagnus angustifolia

Among the oxidized lipids in the seed oil of the oliveElaeagnus angustifolia we have detected six epoxy acids and five hydroxy acids, of these 12-hydroxyoctadeca-8,10-dienone being new. Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan, Tashkent, fax (3712) 89 14 75. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 715–719, November–December, 1994.     

Oxygenated fatty acids of the seeds ofElaeagnus angustifolia

Among the oxidized lipids in the seed oil of the oliveElaeagnus angustifolia we have detected six epoxy acids and five hydroxy acids, of these 12-hydroxyoctadeca-8,10-dienone being new.Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan, Tashkent, fax (3712) 89 14 75. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 715–719, November–December, 1994.     

GC-MS analysis of hydroxy and epoxy acids from seed oil of Hippophaë rhamnoides

By the GC-MS method using a packed column, in the mixture of TMS derivatives of hydroxy acid methyl esters obtained from the seed oil of the sea buckthorn, in ten chromatographic peaks (CPs) 13 monohydroxy compounds have been characterized by their mass spectra, the main ones being derivatives of dimorphecolic and coriolic acids. Structures are proposed for four dihydroxy acids of the C₁₇–C₂₀ series. The mixture of methyl esters of di- and tetra-TMS derivatives obtained from the mixture of epoxy acids from the same source has been analyzed by a similar method. In seven CPs, 11 compounds, reflecting the presence of nine epoxy acids in the initial mixture, have been characterized by their mass spectra. The main component of the mixture was 15,16-epoxyoctadeca-9,12-dienoic acid.     

GC-MS analysis of hydroxy and epoxy acids from seed oil of Hippopha? rhamnoides

By the GC-MS method using a packed column, in the mixture of TMS derivatives of hydroxy acid methyl esters obtained from the seed oil of the sea buckthorn, in ten chromatographic peaks (CPs) 13 monohydroxy compounds have been characterized by their mass spectra, the main ones being derivatives of dimorphecolic and coriolic acids. Structures are proposed for four dihydroxy acids of the C₁₇–C₂₀ series. The mixture of methyl esters of di- and tetra-TMS derivatives obtained from the mixture of epoxy acids from the same source has been analyzed by a similar method. In seven CPs, 11 compounds, reflecting the presence of nine epoxy acids in the initial mixture, have been characterized by their mass spectra. The main component of the mixture was 15,16-epoxyoctadeca-9,12-dienoic acid.Institute of the Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 626–634, September–October, 1989.     

Lipids of the seeds ofSecurinega suffruticosa

The lipid composition of the seeds ofSecurinega suffruticosa (Euphorbiaceae) has been studied, and eight classes of lipids have been identified with a predominance of triacylglycerols; the fatty acid compositions and structures of the triacylglycerols have been determined. Among the hydroxy acids of the hydroxyacylglycerols 13 components belonging to saturated, monoenic, and dienic acids of the C₁₇, C₁₈, and C₂₀ series have been identified; 12-hydroxyheptadecanoic and 12-hydroxyeicosanoic acids are new.Institute of the Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 277–281, May–June, 1986.     

Sterols from the Stems of Momordica charantia

A new sterol, 5α,6α‐epoxy‐3β‐hydroxy‐(22E,24R)‐ergosta‐8,22‐dien‐7‐one ( 1 ), together with eight known sterols, 5α,6α‐epoxy‐(22E,24R)‐ergosta‐8,22‐diene‐3β,7α‐diol ( 2 ), 5α,6α‐epoxy‐(22E,24R)‐ergosta‐8,22‐diene‐3β,7β‐diol ( 3 ), 5α,6α‐epoxy‐(22E,24R)‐ergosta‐8(14),22‐diene‐3β,7α‐diol ( 4 ), 3β‐hydroxy‐(22E,24R)‐ergosta‐5,8,22‐trien‐7‐one ( 5 ), ergosterol peroxide ( 6 ), clerosterol ( 7 ), decortinol ( 8 ), and decortinone ( 9 ), were isolated from the stems of Momordica charantia. Their structures were elucidated by mean of extensive spectroscopic methods, including ¹H, ¹³C, 2D‐NMR and HR‐EI‐MS, as well as comparison with the literature data. Compounds 1 , 4 , 5 , 8 , and 91 were not cytotoxic against the SK‐Hep 1 cell line.     

pH-Metric studies on the binary and ternary complexes of oxovanadium(IV)

The interaction of oxovanadium(IV) with some hydroxy acids, salicylic (SA), 5-sulphosalicylic (SSA) and 8-hydroxyquinoline-5-sulphonic (HQSA) acids, has been studied potentiometrically. Further, pH-metric studies of the ternary systems, VO²⁺?HQSA-dicarboxylic or hydroxy acids (where dicarboxylic acids = phthalic and maleic acids and hydroxy acids =SA andSSA) have been carried out and the formation of 1∶1∶1 mixed complexes inferred from the potentiometric curves. The equilibrium, chelate formation and hydrolysis constants have been calculated in the case of binary systems. The ternary complexes have been found to be more stable as indicated by their formation constants.     

Noroleanane Triterpenoids from the Aerial Parts of Lantana camara

Two novel triterpenoids, lantadienone ( 1 ) and camaradienone ( 2 ), were isolated from the aerial parts of Lantana camara, along with seven known compounds, lantadene A, lantadene B, β‐sitosterol 3‐(β‐D ‐glucopyranoside), camaric acid, lantanilic acid, lantanolic acid, and camangeloyl acid. Their structures were elucidated as (3β,22β)‐3,25‐epoxy‐3‐hydroxy‐22‐{[(2Z)‐2‐methyl‐1‐oxobut‐2‐enyl]oxy}‐28‐noroleana‐12,17‐dien‐11‐one ( 1 ) and (3β)‐3,25‐epoxy‐3‐hydroxy‐28‐noroleana‐12,17‐dien‐11‐one ( 2 ), respectively, by means of spectral studies. The triterpenoids 1 and 2 represent 28‐noroleananes oxidized at C(11) and C(22) or at C(11), reported for the first time.     

A Highly Stereoselective Synthesis of Glycidic Amides Based on a New Class of Chiral Sulfonium Salts: Applications in Asymmetric Synthesis

A new type of chiral sulfonium salts that are characterized by a bicyclic system has been designed and synthesized from α‐amino acids. Their corresponding ylides, which were prepared by basic treatment of the sulfonium salts, reacted smoothly with a broad array of simple and chiral aldehydes to provide trans‐epoxy amides in reasonable to very good yields and excellent stereoselectivities (>98 %). The obtained epoxy amides were found to be useful as synthetic building blocks. Thus, they were reduced into their corresponding epoxy alcohols and subjected to oxirane‐ring‐opening reactions with different types of nucleophiles.     

Neutral lipids of the seeds ofPhlomis oreophilla andPh. regelii

The lipid and fatty acid compositions of the seeds ofPhlomis oreophilla andPh. regelii (familyLabiatae) have been studied. The lipids ofPh. oreophilla are enriched with linoleic acid and those ofPh. regelii with oleic acid. Laballenic acid is present in the total acids of the triacylglycerides and the free fatty acids of both species, being concentrated in the free acids. The epoxy acids ofPh. oreophilla are represented by 9,11-epoxystearic, vernolic, coronaric, and 15,16-epoxylinoleic acids.Institute of the Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 561–565, September–October, 1983.     

Ring pucker in dihydroaromatic epoxides: The molecular structure ofr-1-hydroxy-t-2-methyl-t,t-3,4-epoxy-1,2,3,4-tetrahydronaphthalene

The crystal structure of the derivative of tetrahydronaphthalene with substituent epoxy, hydroxyl, and methyl groups in the more saturated ring (r-1-hydroxy-t-2-methyl-t,t-3,4-epoxy-1,2,3,4-tetrahydronaphthalene) has been determined. The hydroxyl and methyl groups are both found to beequatorial. The crystal structure is characterized by chains of molecules linked by O-H O hydrogen bonds involving the hydroxyl groups; these hydrogen bonds lie approximately parallel to theb axis. The conformations of the epoxide-bearing rings in various hydroxy epoxides are compared and shown to be similar.     

Terpenoids from the Flower of Cacalia Tangutica

A thorough investigation of Cacalia tangutica (Franch.) Hand‐Mazz afforded two new epimeric eremophilane sesquiterpenoids, 7β‐ H‐3α‐angeloyloxy‐9‐ene‐11,12‐epoxy‐8‐oxoeremophilane ( 1 ) and 7α‐H‐3α‐angeloyloxy‐9‐ene‐11,12‐epoxy‐8‐oxoeremophilane ( 2 ), as well as four known sesquiterpenes, petasol ( 3 ), oplopanone ( 4 ), 4,5‐epoxy‐β‐caryophyllene ( 5 ), 4(15)‐eudesmene‐1β,6α‐diol ( 6 ), and three known monoterpenes, 1β,2α‐dihydroxy‐p‐menth‐5‐ene ( 7 ), 5α‐hydroxy‐2‐oxo‐p‐menth‐6(1)‐ene ( 8 ), 5β‐hydroxy‐2‐oxo‐p‐menth‐6(1)‐ene ( 9 ), and two known triterpenes, maniladiol 3‐O‐palmitate ( 10 ), taraxasteryl palmitate ( 11 ). The new compounds were characterized by means of spectroscopic methods including 1D, 2D NMR and HRESIMS, and the known ones were established on the basis of comparing their NMR data with those of the corresponding compounds in the literature. In addition, cytotoxicity against selected cancer cells (HL‐60, HO‐8910 and A‐549) of compounds 1 ‐ 4 , 6 , 7 , 10 were measured in vitro.     

Monolayer properties of fatty acids : II. Surface vapor pressure and the free energy of compression

The properties of monolayers spread at the air-water interface were measured for saturated, unsaturated, and hydroxy fatty acids, differing in the type and degree of unsaturation, geometric isomerism, and position of unsaturated and hydroxy groups. Surface vapor pressures, reflecting the equilibrium between “gaseous” and “liquid” monolayer states were determined, as were the free energies of compression, ΔF_c, from essentially infinite dilution (100,000 Ų/molecule) to the area per molecule, A_e at the equilibrium spreading pressure, π_e. Surface vapor pressures and free energies of compression for saturated and unsaturated fatty acids with a double bond, or bonds, change in a manner expected because of chain-chain interactions. Hydroxy and acetylenic acids produce relatively high surface vapor pressures, despite their tendency for strong chain-chain interaction. It is concluded that chain-water interactions are very significant for the acetylenic and hydroxy acids and less so for the saturated and ethylenic acids.     

Reaction of γ‐Hydroxy‐N‐[1‐(dimethylcarbamoyl)ethyl]butanamides under the ‘Direct Amide Cyclization’ Conditions

The preparation of the title compounds was achieved via the ‘azirine/oxazolone method’ starting from the corresponding γ‐hydroxy acids. Upon subjecting the γ‐hydroxy‐N‐[1‐(dimethylcarbamoyl)ethyl]butanamides 4 to the so‐called ‘direct amide cyclization’ (DAC) conditions, chlorinated acids 11 or imino lactones 12 were obtained as the sole products instead of the expected cyclodepsipeptides A or their cyclodimers (Scheme 4). Variation of the substituents in 4 did not affect the outcome of the reaction and a mechanism for the formation of both products from the intermediate oxazolone 13 has been proposed. Under the acidic conditions of the DAC, the imino lactones are formed as their HCl salts 12 , which, in polar solvents or on silica gel, reacted further to give the chlorinated acids 11 . Stabilization of the imino lactones was achieved by increasing the substitution in the five‐membered ring, and their structure, in the form of the hydrochlorides, was established independently by X‐ray crystallography (Fig. 4). A derivative 15 of the imino lactone 12a was prepared by the reaction with the 2H‐azirin‐3‐amine 10a ; its structure was also established by an X‐ray crystal‐structure determination (Fig. 3). Furthermore, the structures of the ω‐chloro acids 11a and 11b were determined by X‐ray crystallography (Fig. 2).     

Characterization of the high molecular mass chlorinated matter in spent bleach liquors (SBL): 3—Mass spectrometric interpretation of aromatic degradation products in SBL

The aromatic content of the high molecular matter in pulp mill bleachery effluents has been characterized after chemical degradation in the laboratory followed by derivatization and gas chromatographic/mass spectrometric analysis. Aromatic molecules with carboxy, hydroxy, methoxy and chloro substituents were separated and identified by recording their computer-reconstructed ion current chromatograms. About 70 aromatic carboxylic acids were tentatively identified as degradation products. Aromatic compounds with hydroxy groups were derivatized to trideuteromethoxy groups in order to distinguish them by mass spectrometry from compounds with naturally occurring methoxy groups. Single and double hydrogen atom transfer between methyl ester and methoxy groups were observed in some molecules and given special attention when they occurred ortho to each other. A methoxy group substituted ortho to a methyl carboxylate resulted in an unusual fragmentation.     

Stereochemistry and Conformation of Skyllamycin,a Non‐Ribosomally Synthesized Peptide from Streptomyces sp. Acta 2897

Skyllamycin is a non‐ribosomally synthesized cyclic depsipeptide from Streptomyces sp. Acta 2897 that inhibits PDGF‐signaling. The peptide scaffold contains an N‐terminal cinnamoyl moiety, a β‐methylation of aspartic acid, three β‐hydroxylated amino acids and one rarely occurring α‐hydroxy glycine. With the exception of α‐hydroxy glycine, the stereochemistry of the amino acids was assigned by comparison to synthetic reference amino acids applying chiral GC‐MS and Marfey‐HPLC analysis. The stereochemistry of α‐hydroxy glycine, which is unstable under basic and acidic conditions, was determined by conformational analysis, employing a combination of data from NOESY‐NMR spectroscopy, simulated annealing and free MD simulations. The simulation procedures were applied for both R‐ and S‐configured α‐hydroxy glycine of the skyllamycin structure and compared to the NOESY data. Both methods, simulated annealing and free MD simulations independently support S‐configured α‐hydroxy glycine thus enabling the assignment of all stereocenters in the structure of skyllamycin and devising the role of two‐component flavin dependent monooxygenase (Sky39) as S‐selective.     

Thrombin Inhibitory Constituents from Duranta repens

The C‐alkylated flavonoids 3,7,4′‐trihydroxy‐3′‐(4‐hydroxy‐3‐methylbutyl)‐5,6‐dimethoxyflavone ( 1 ), 3,7‐dihydroxy‐3′‐(4‐hydroxy‐3‐methylbutyl)‐5,6,4′‐trimethoxyflavone ( 2 ) and the trans‐clerodane diterpenoids 6β‐hydroxy‐15,16‐epoxy‐5β,8β,9β,10α‐cleroda‐3,13(16),14‐trien‐18‐oic acid ( 3 ) and 2β‐hydroxy‐15,16‐epoxy‐5β,8β,9β,10α‐cleroda‐3,13(16),14‐trien‐18‐oic acid ( 4 ) were isolated from Duranta repens. Their structures and the relative configuration of 3 and 4 were determined by spectroscopic methods (¹H‐ and ¹³C‐NMR, IR, and MS) and 2D‐NMR experiments. The known flavonoid 5 is also reported for the first time from this species. The compounds 1 , 3 , and 5 showed significant enzyme‐inhibitory activity against thrombin.     

Generalized Method for the Production of 1,3‐Benzoxazine, 1,3‐Benzothiazine,and Quinazoline Derivatives from 2‐(Hydroxy,Thio, or Amino) Aromatic Acids Using Triphenylphosphine Thiocyanogen

Abstract

A modified one‐pot method was developed for the synthesis of 1,3‐benzoxazines, in which the preparation of unstable thiocyanogen was omitted. The method was found to be general for substituted (methyl, methoxy, halo, and hydroxy) 2‐hydroxy benzoic acids and 2‐hydroxy naphthoic acids. The method was extended to 2‐thio, 2‐amino, and N‐methyl aminobenzoic acid with which the synthesis of 1,3‐benzothiazine and quinazoline derivatives has been achieved, respectively. It was also found that 3‐hydroxypyridine‐2‐carboxylic acid and 2‐hydroxynicotinic acid using a modified method gave 2‐thioxo‐2,3‐dihydro‐4H‐pyrido[2,3‐e][1,3]oxazin‐4‐one and 2‐thioxo‐2,3‐dihydro‐4H‐pyrido[3,2‐e][1,3]oxazin‐4‐one, respectively. The structures of the new compounds were confirmed by the analysis of their IR, ¹H, and ¹³C NMR spectra.     

Bile acids and their oxo derivatives: Potential inhibitors of carbonic anhydrase I and II,androgen receptor antagonists and CYP3A4 substrates

Some biological properties of bile acids and their oxo derivatives have not been sufficiently investigated, although the interest in bile acids as signaling molecules is rising. The aim of this work was to evaluate physico‐chemical parametar b (slope) that represents the lipophilicity of the examined molecules and to investigate interactions of bile acids with carbonic anhydrase I, II, androgen receptor and CYP450s. Thirteen candidates were investigated using normal‐phase thin‐layer chromatography in two solvent systems. Retention parameters were used in further quantitative structure–activity relationship analysis and docking studies to predict interactions and binding affinities of examined molecules with enzymes and receptors. Prediction of activity on androgen receptor showed that compounds 3α ‐hydroxy‐12‐oxo‐5β ‐cholanoic and 3α ‐hydroxy‐7‐oxo‐5β ‐cholanoic acid have stronger antiandrogen activity than natural bile acids. The inhibitory potential for carbonic anhydrase I and II was tested and it was concluded that molecules 3α ‐hydroxy‐12‐oxo‐5β ‐cholanoic, 3α ‐hydroxy‐7‐oxo‐5β ‐cholanoic, 3,7,12‐trioxo‐5β ‐cholanoic acid and hyodeoxycholic acid show the best results. Substrate behavior for CYP3A4 was confirmed for all investigated compounds. Oxo derivatives of bile acids show stronger interactions with enzymes and receptors as classical bile acids and lower membranolytic activity compared with them. These significant observations could be valuable in consideration of oxo derivatives as building blocks in medicinal chemistry.