Methyl Homologues of Methyl Jasmonate and Methyl Dihydrojasmonate (Hedione®) from Sorbyl Alcohol

Treatment of cycloalkanone dimethyl acetals 3 – 6 with sorbyl alcohol (=(2E,4E)‐hexa‐2,4‐dien‐1‐ol; 1 ) in the presence of acids afforded the novel cycloalkenones 8, 9, 11 , and 13 via a domino reaction (Claisen rearrangement with intramolecular ene reaction and retro‐ene reaction). Cyclopentenone 8 was readily transformed into 14 and 15 , methyl homologues of racemic methyl jasmonate ( 16 ) and methyl dihydrojasmonate (=Hedione®; 17 ), respectively. The organoleptic properties of 14 and 15 are also discussed.     

Exploring the Border between Concerted and Two‐Step Pathways of 1,3‐Dipolar Cycloadditions of Organic Azides to Cyclic Ketene N,X‐Acetals. – Synthesis and 15N‐NMR Spectra of Zwitterions and Spirocyclic Cycloadducts

Cyclic ketene N,X‐acetals 1 are electron‐rich dipolarophiles that undergo 1,3‐dipolar cycloaddition reactions with organic azides 2 ranging from alkyl to strongly electron‐deficient azides, e.g., picryl azide ( 2L ; R¹=2,4,6‐(NO₂)₃C₆H₂) and sulfonyl azides 2M – O (R¹=XSO₂; cf. Scheme 1). Reactions of the latter with the most‐nucleophilic ketene N,N‐acetals 1A provided the first examples for two‐step HOMO(dipolarophile)–LUMO(1,3‐dipole)‐controlled 1,3‐dipolar cycloadditions via intermediate zwitterions 3 . To set the stage for an exploration of the frontier between concerted and two‐step 1,3‐dipolar cycloadditions of this type, we first describe the scope and limitations of concerted cycloadditions of 2 to 1 and delineate a number of zwitterions 3 . Alkyl azides 2A – C add exclusively to ketene N,N‐acetals that are derived from 1H‐tetrazole (see 1A ) and 1H‐imidazole (see 1B , C ), while almost all aryl azides yield cycloadducts 4 with the ketene N,X‐acetals (X=NR, O, S) employed, except for the case of extreme steric hindrance of the 1,3‐dipole (see 2E ; R¹=2,4,6‐(^tBu)₃C₆H₂). The most electron‐deficient paradigm, 2L , affords zwitterions 16D , E in the reactions with 1A , while ketene N,O‐ and N,S‐acetals furnish products of unstable intermediate cycloadducts. By tuning the electronic and steric demands of aryl azides to those of ketene N,N‐acetals 1A , we discovered new borderlines between concerted and two‐step 1,3‐dipolar cycloadditions that involve similar pairs of dipoles and dipolarophiles: 4‐Nitrophenyl azide ( 2G ) and the 2,2‐dimethylpropylidene dipolarophile 1A (R, R=H, ^tBu) gave a cycloadduct 13 H , while 2‐nitrophenyl azide ( 2 H ) and the same dipolarophile afforded a zwitterion 16A . Isopropylidene dipolarophile 1A (R=Me) reacted with both 2G and 2 H to afford cycloadducts 13G , J ) but furnished a zwitterion 16B with 2,4‐dinitrophenyl azide ( 2I) . Likewise, 1A (R=Me) reacted with the isomeric encumbered nitrophenyl azides 2J and 2K to yield a cycloadduct 13L and a zwitterion 16C , respectively. These examples suggest that, in principle, a host of such borderlines exist which can be crossed by means of small structural variations of the reactants. Eventually, we use ¹⁵N‐NMR spectroscopy for the first time to characterize spirocyclic cycloadducts 10 – 14 and 17 (Table 6), and zwitterions 16 (Table 7).     

Biocatalytic Generation of Molecular Diversity: Modification of Ginsenoside Rb1 by β‐1,4‐Galactosyltransferase and Candida antarctica Lipase,Part 4

A series of specific derivatives of the complex protopanaxadiol glycoside ginsenoside Rb₁ ( 1 ) were prepared by catalysis of two unrelated enzymes: the β‐1,4‐galactosyltransferase from bovine colostrum (GalT) and the lipase B from Candida antarctica (Novozym ^® 435). Both of the enzymes showed the expected regioselectivity towards specific glucose OH groups (i.e., OH C(4) for GalT and preferentially the primary OH C(6) for Novozym ^® 435), accompanied by a nonpredictable ‘site selectivity' for the gentiobiose disaccharide unit linked at C(20) of the dammarane skeleton. The galactosylated products 1a – e and the acetylated products 1f – h were isolated by HPLC and fully characterized by extensive MS and NMR analysis.     

Nature of the antimicrobial activity of Lactobacillus caseiBifidobacterium bifidum and Bifidobacterium animalis against foodborne pathogenic and spoilage microorganisms

The antimicrobial activities as well as the nature of the inhibitory compounds obtained from Lactobacillus casei, Bifidobacterium bifidum and Bifidobacterium animalis strains were assayed on foodborne pathogenic – Staphyloccoccus aureus subsp. aureus (CCUG ATCC® 25926?) and Escherichia coli (ATCC® 25922?) – and spoilage microorganisms – Pseudomonas aeruginosa (ATCC® 27853?). Test producer strains showed inhibitory effect on all indicator microorganisms in diffusion of cell-free concentrated supernatant by agar in well methods (10.0–22.5 mm) in periods of 24, 48 and 72 h. Inhibitory compounds showed no sensitivity to the action of proteolytic enzyme trypsin and were completely inactivated by adjusting the pH of the cell-free 20 × concentrated supernatant to 7.0. The results demonstrated that antimicrobial substances do not have proteinaceous nature and are caused by the action of organic acids with decreasing medium pH.     

Amino‐Claisen Rearrangements and Diels‐Alder Reactions of Ketene N,O‐Acetals: Reactivity Studies. On the Way to a Novel Tandem Process?

We report the synthesis of N‐benzyl‐N‐[(E)‐buta‐1,3‐dienyl]propanamide ( 6 ) and its corresponding O‐silyl‐substituted ketene N,O‐acetal 7 and their Diels‐Alder reaction. Propanamide 6 reacted smoothly, whereas the yield obtained from 7 was low, probably due to polymerization of the dienophile induced by electron transfer. The ketene N,O‐acetals 27a – g were synthesized starting from the corresponding benzamides 25a – e (Scheme 9). The ketene N,O‐acetals 27a – g showed increased stabilities and underwent amino‐Claisen rearrangements under thermal conditions. Using catalysts, interesting side reactions leading either to the annulated systems rac‐ 35 – 37 or to a β‐lactam rac‐ 34 were observed.     

Enzymatic Approach to and Odor Description of the Twelve Enantiomerically Pure Isomers of Pelargene®

Pelargene^® is a commercial fragrance sold as a mixture of three regioisomeric pyran derivatives ( 1 – 3 ). The enantiomers of each of the two possible diastereoisomers of 1 – 3 were prepared by means of a biocatalyzed approach, and the odor properties of the twelve isolated stereoisomers were evaluated.     

Spirocyclic Ethers Related to Ambrox®: Synthesis and Structure‐Odor Relationships

The seven spirocyclic ethers 4 – 10 , related to the tricyclic odorant Ambrox ^® ( 1 ) and its diastereoisomers 2 and 3 , were synthesized. Their odoriferous activity/inactivity was correlated with the steric accessibility of the ether O‐atom, calculated by computer‐aided molecular modeling. The olfactory properties of the active compounds are discussed.     

Internal Nucleophilic Termination in Acid‐Mediated Polyene Cyclizations. Part 3

Treatment of the unsaturated allenic alcohols (E)‐ 7 , (Z)‐ 7, 10, 13 , and 19 with an excess of FSO₃H in 2‐nitropropane at ?90° to ?30° afforded, in 68–85% yield, diastereoisomer mixtures of racemic tricyclic ethers 14a – d and 20a – d , respectively (Schemes 3 and 5), with high stereoselectivity (see Table and Scheme 6). These stereospecific transformations represent the first reported examples of an acid‐mediated polyene cyclization, in which an alkene is the initiating group and an allenic alcohol serves as the internal terminator. In close analogy to our earlier work, a nonsynchronous process is postulated, whereby the stereochemical course of cyclization is directed by the conformational structure of an intermediate cyclohexyl cation (see Schemes 3 and 6). In addition, the organoleptic properties of 14c and 20c , racemic didehydro and methyl didehydro analogues, respectively, of the known odorant Ambrox^® ((?)‐ 4f ), are briefly discussed.     

Stossaktivierungsspektren von 2-Alkoxybenzoesäuremethylestern

The CA spectra of the [M – Alkene]⁺·- and [M – Alkyl]⁺- ions from several 2-alkoxy-benzoic acid methyl esters and two 2H labelled 2-ethoxybenzoic acid methyl esters are discussed. The results show that the [M – alkene]⁺· ions decomposing after 10^?5 s by collisional activation have the structure of the ionised salicylic acid methyl ester. Moreover, it is demonstrated that the [M – methyl]⁺ ions from the 2-ethoxy esters exist in two different structures. No equilibration between these two structures is observed even after 10^?5s. Structures for several daughter ions generated by collisional activation are discussed using the CA spectra of the labelled compounds.     

Ring-opened analogues of Ambrox®: Synthesis and Structure-Odour relationships

Eight bicyclic ether derivatives 11 – 18 , related to the tricyclic odorant Ambrox^® ( 1 ) and its analogues 2 – 6 by formal heteroring-opening, have been prepared; their odoriferous activity/in activity is correlated with the steric accessibility of the ether O-atom, calculated by computer-aided molecular modeling.     

Synthesis of Tricyclic Ketones with Sesquiterpene Skeletons by Acid-Catalyzed Rearrangement of β-Monocyclofarnesol

Starting from dihydro-β-ionone ( 6 ) a mixture of three tricyclic ketones with sesquiterpene skeletons 14 , 15 , and 16 was prepared by Wittig-Horner reaction with triethyl phosphonoacetate, Red-Al^® reduction, acid-catalyzed rearrangement of the resulting β-monocyclofarnesol ( 7 ), alkaline hydrolysis of the formates 8 – 10 , and subsequent molybdenium-catalyzed oxidation. The mechanistic background of the acid-catalyzed rearrangement of β-monocyclofarnesol ( 7 ) is discussed in detail. The resulting tricyclic ketones 14 – 16 exhibit intense woody odor notes with peppery vetiver or camphoraceous cedarwood aspects.     

Peroxide‐mediated crosslinking of poly(ethylene oxide)

The crosslinking of poly(ethylene oxide) (PEO) with a difunctional peroxide such as 2,5‐bis(tert‐butylperoxy)‐2,5‐dimethylhexane (Luperox 101) may proceed through at least two different pathways. Thus, the thermally formed alkoxy radicals abstract hydrogen from PEO, and the resulting PEO radicals may combine or react with the peroxide radicals to give ether or acetal crosslinks. However, these reactions also produce noncrosslinking acetals and vinyl ethers. The acetals may react further with peroxy or other radicals and yield orthoesters and ketene acetals. These and similar groups, in the presence of dilute acids, are susceptible to acid hydrolysis, leading to the disintegration of the gels. The gels, upon swelling in dilute acids, undergo a slow degradation process that is not observed for unmodified PEO. The acid hydrolysis is confirmed by a combination of size exclusion chromatography and dynamic mechanical analysis. IR analysis shows the presence of hydroxyl end groups and the presence of carboxylates rather than aldehyde groups, this is consistent with orthoesters and ketene acetal intermediates. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3021–3026, 2002     

Über primäre Disazofarbstoffe mit Aminonaphtol-sulfonsäuren

Disazo dyes from 6-amino-1-hydroxy-naphthalene-3-sulfonic acid (J acid) were synthesized by coupling ortho-hydroxy monoazo dyes with different diazonium compounds in acid medium (dyes No 3 – 14 . A second coupling to the ortho position of the amino group was also possible with the copper complexes of o,o' -dihydroxy monoazo dyes from 8-amino-1-hydroxynaphthalene-3,6-disulfonic acid (H acid) dyes No 19 – 22 ). This is a reversal of the well known rule that the formation of disazo dyes with aminonaphthol-sulfonic acids is only practicable when an acid coupling is followed by an alkaline one. 5-Amino-1-hydroxy-naphthalene-3-sulfonic acid (M acid), which is said to form no disazo dyes, could be coupled twice with several diazonium compounds to yield disazo dyes (dyes No 24 , 26 , 27 , 29 ).     

Efficient and Selective Formation of Mixed Acetals by Nafion‐H SAC‐13 Silica Nanocomposite Solid Acid Catalyst

Abstract

Various types of hydroxy compounds can readily be converted to the corresponding mixed acetals with dialkoxymethanes in the presence of SAC‐13 solid superacid. The transformation is almost instantaneous, product acetals are isolated in good to excellent yields, and the catalyst can be reused with minor loss of activity. Comparative studies were also carried out with p‐toluenesulfonic acid and BF₃ · OEt₂.     

A new design of cleavable acetal‐containing amphiphilic block copolymers triggered by light

We report a new design of photolabile acetal‐containing amphiphilic block copolymers. Acetals as protecting groups for carbonyls or diols can be hydrolyzed under acidic condition but very stable with respect to hydrolysis at pH > 7. When combining light‐capturing chromophores with acetals, the hydrolysis of acetals can be activated by light to design dual responsive acetal‐containing polymers. Using acetalization reaction of 2,3‐dihydroxypropyl methacrylate with benzaldehyde derivatives, two new acetal‐containing photolyzable monomers have been designed. Comparable to commonly used photolabile monomers containing nitrobenzyl esters, the two acetal‐containing monomers are easy to polymerize using atom transfer radical polymerization with excellent molecular weight and dispersity control. We studied the cleavage kinetics and mechanism of acetal groups in both monomers and polyethylene oxide (PEO)‐containing amphiphilic block copolymers using ¹H NMR and UV–vis spectroscopy. o‐Nitrobenzaldehyde acetal showed a Norrish Type II rearrangement to form benzoic ester; while, 2,5‐dimethoxy benzaldehyde acetal was photolabile to completely release 2,3‐dihydroxypropyl methacrylate. The photocleavage of acetals is a zero‐order reaction in regardless of molecular states of acetals; while, the acid‐cleavage of acetals proves to be a first‐order kinetics and the cleavage becomes much slower for polymers. The self‐assembly of acetal‐containing amphiphilic block copolymers and the acid‐/light‐controlled dissociation of their vesicles have been investigated. We demonstrate that those acetal‐containing polymers are potentially useful as smart drug delivery systems where the release kinetics of payloads is tunable using light and pH as triggers. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 1815–1824     

Efficient Synthesis of α‐Benzylidene‐γ‐methyl‐γ‐butyrolactones

A concise synthesis of α‐benzylidene‐γ‐methyl‐γ‐butyrolactones 5a – g from substituted benzaldehydes is described. Compounds 1a – g on reaction with phosphorane 2 , provide the pentenoates 3a – g , which can be hydrolyzed to the acids 4a – g . The latter are cyclized to the corresponding butyrolactones 5a – g in excellent yields. The pentenoates 3a – g , on acid catalyzed cyclization, also provide 5a – g in very high yields.     

Lewis Acid‐Mediated Addition of Amino Acid‐Substituted α‐Allylsilanes to Aromatic Acetals

Unnatural amino acids extend the pharmacological formulator's toolkit. Strategies to prepare unnatural amino acid derivatives using Lewis acid‐activated allylsilane reactions are few. In this regard, we examined the utility of allylsilanes bearing an amino acid substituent in the reaction. Diastereoselective addition of methyl 2‐(N‐PG‐amino)‐3‐(trimethylsilyl)pent‐4‐enoate and methyl (E)‐2‐(N‐PG‐amino)‐3‐(trimethylsilyl)hex‐4‐enoate (PG=protecting group), 2 and 13 , respectively, to aromatic acetals in the presence of Lewis acids is described. Of those examined, TiCl₄ was found to be the most effective Lewis acid for promoting the addition. At least 1 equiv. of TiCl₄ was required to achieve high yields, whereas 2 equiv. of BF₃?OEt₂ were required for comparable outcomes. Excellent selectivity (>99% syn/anti) and high yield (up to 89%) were obtained with halo‐substituted aromatic acetals, while more electron‐rich electrophiles led to both lower yields and diastereoselectivities.     

Nouvelle méthode de préparation d'éthers vinyliques à partir d'acétals

A new way to vinylic ethers from acetals Acetals react at low temperatures in presence of a Lewis acid (aluminium chloride or magnesium bromide) with tertiary amine to give in good yields the vinylic ethers corresponding to the elimination of one molecule of alcohol.     

Internal Nucleophilic Termination in Acid‐Mediated Polyene Cyclizations Part 4

Treatment of the unsaturated bicyclic homoallylic alcohols (E)‐ and (Z)‐ 5 and (Z)‐ and (E)‐ 10 and allenic alcohol 16 with an excess of ClSO₃H in 2‐nitropropane or CH₂Cl₂ at − 80° afforded, in moderate yields (ca. 30–70%), diastereoisomer mixtures of racemic tetracyclic ethers 12a – c (Table 1) and 17a,b (Table 2), respectively. These kinetically controlled stereospecific transformations are believed to proceed via concerted or nonconcerted pathways (see Schemes 4 and 6) and the results are fully consistent with our earlier work. Representing novel didehydro bridged analogues of known, olfactively active labdane tricyclic ethers, the organoleptic properties of 12a – c and 17a,b are briefly described, especially those of 12c which, in the context of structure–activity studies, is a racemic didehydro analogue of the known ambergris odorant Ambrox^®.     

Nucleotides,Part LXVIII,Acetals as New 2′‐O‐Protecting Functions for the Synthesis of Oligoribonucleotides: Synthesis of Monomeric Building Units and Oligoribonucleotides

For the efficient synthesis of oligoribonucleotides by the 5′‐O‐(4,4′‐dimethoxytrityl) phosphoramidite approach, the 2′‐O‐[1‐(benzyloxy)ethyl]acetals 56 – 67 were investigated. Studies with the 2′‐O‐[1‐(benzyloxy)ethyl]‐5′‐O‐(dimethoxytrityl)ribonucleoside 3′‐phosphoramidites 56 – 59 gave, however, only reasonable results. The oligoribonucleotides obtained showed some impurities since the acid stabilities of the acetal and dimethoxytrityl functions are too close to guarantee a high selectivity. A combination of new acid‐labile protected 2′‐O‐protecting groups with the 2‐(4‐nitrophenyl)ethyl/[2‐(4‐nitrophenyl)ethoxy]carbonyl (npe/npeoc) strategy for base protection was more successful. The synthesis and physical properties of the monomeric building units and their intermediates 8 – 67 and the conditions for the automated generation of homo‐ and mixed oligoribonucleotides is described. The new 2′‐acetal protecting group could be cleaved off in a two step procedure and was designed for levelling their stability with regard to the attached nucleobase as well. Therefore, we used the 1‐{{3‐fluoro‐4‐{{[2‐(4‐nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl (fnebe) moiety for the protection of 2′‐OH of uridine, and for that of 2′‐OH of A, C, and G, the 1‐{{4‐{{[2‐(4‐nitrophenyl)ethoxy]carbonyl}oxy}benzyl}oxy}ethyl (nebe) residue. After selective deprotection by β‐elimination induced by a strong organic base like DBU, the remaining activated acetal was hydrolyzed under very mild acidic protic conditions, which reduced 2′‐3′ isomerization and chain cleavage. Also storage, handling, and purification of the chemically and enzymatically sensitive oligomers was simplified by this approach.