Lipids ofBryonia alba

The lipid composition of the roots ofBryonia alba (Cucurbitaceae) have been studied: It consists of fractions of 3-acyloxy-24-alkyl(alkenyl)-cholest-7-enes (I), triacylglycerols (II), 1,2-diacyl-3-monoglycopyranosyl-sn-glycerols (III), 1,2-diacyl-3-diglycopyranosyl-sn-glycerols (IV), 1,3-bis(3-sn-phosphatidyl)glycerols (V), 3-sn-phosphatidylethanolamines (VI), 3-sn-phosphatidylcholines (VII), and methyl esters of fatty acids (VIII). The amount of unsaturated fatty acids in the lipid fractions (I–VIII) is 60–94%, the main component being linolenic acid.     

Lipids ofBryonia alba

The lipid composition of the roots ofBryonia alba (Cucurbitaceae) have been studied: It consists of fractions of 3-acyloxy-24-alkyl(alkenyl)-cholest-7-enes (I), triacylglycerols (II), 1,2-diacyl-3-monoglycopyranosyl-sn-glycerols (III), 1,2-diacyl-3-diglycopyranosyl-sn-glycerols (IV), 1,3-bis(3-sn-phosphatidyl)glycerols (V), 3-sn-phosphatidylethanolamines (VI), 3-sn-phosphatidylcholines (VII), and methyl esters of fatty acids (VIII). The amount of unsaturated fatty acids in the lipid fractions (I–VIII) is 60–94%, the main component being linolenic acid.A. L. Mndzhoyan Institute of Fine Organic Chemistry of the Academy of Sciences of the Armenian SSR, Erevan. Translated from Khimiya Pridodnykh Soedinenii, Vol. 6, pp. 781–785, November–December, 1980.     

Achiral counterion control of enantioselectivity in a Brønsted acid-catalyzed iodolactonization

Highly enantioselective halolactonizations have been developed that employ a chiral proton catalyst-N-iodosuccinimide (NIS) reagent system in which the Br?nsted acid is used at catalyst loadings as low as 1 mol %. An approach that modulates the achiral counterion (equimolar to the neutral chiral ligand-proton complex present at low catalyst loadings) to optimize the enantioselection is documented for the first time in this transformation. In this way, unsaturated carboxylic acids are converted to γ-lactones in high yields (up to 98% ee) using commercially available NIS.     

13C-NMR Spectra of 2- and 3-Phthalimido-3(2)-Benzimidazolylpropanoic Acid and 2- and 3-Phthalimidobenzimidazopyrrolone,Reaction Products of Phthaloylaspartic Anhydride with Ortho-Phenylenediamine

Two pairs of isomers of 3- and 2-phthalimido-3(2)benzimidazolylpropanoic acid (V and VI) and 2- and 3-phthalimidobenzimidazopyrrolone (VII and VIII) were produced from the reaction of phthaloylaspartic anhydride (I) with o-phenylenediamine (II). The ¹³C-NMR spectra of V and VI both showed 11 carbon signals indicating that the structures of their benzimidazole groups were symmetric. Isomers V and VI were easily distinguished from each other by the chemical-shift-differences (Δδ) of the methylene carbon and the methine carbon. Compounds VII and VIII displayed 14 carbon signals and no longer showed the symmetric structure of the benzimidazole moity, The chemical-shift-differences (Δδ) between methylene carbon and methine carbon in pyrrolones of VII and VIII can also be used to distinguish VII from VIII. The Δδ of compound VII is less than that of compound VIII.     

Synthesis of phthalimidines. Acid-catalyzed cyclodehydration versus cyclodeamination of γ-hydroxyamides obtained from dilithio-N-substituted benzamides and ketones

An earlier method of preparation of γ-hydroxyamides from N-substituted benzamides and ketones or aldehydes by means of n-butyllithium was improved and extended. The γ-hydroxyamides were found to undergo cyclodehydration to form γ-lactams with relatively strong acids, but cyclodeamination formed γ-lactones with relatively weak acids; the γ-lactams are substituted phthalimidines. The predominant course of cyclization was dependent also on the structure of the γ-hydroxyamide. Certain γ-hydroxyamides afforded phthalimidines with cold, concentrated sulfuric acid whereas certain others yielded γ-lactones with this acid. The latter γ-hydroxyamides, however, produced phthalimidines with the stronger acid, perchloric acid. The cyclodehydration reaction furnished a convenient and, apparently, quite general method for the synthesis of 2,3,3-trisubstituted or 2,3-disubstituted phthalimidines. Mechanisms are considered.     

Highly Regio‐ and Enantioselective Synthesis of γ,δ‐Unsaturated Amido Esters by Catalytic Hydrogenation of Conjugated Enamides

An efficient and highly regio‐ and enantioselective catalytic asymmetric hydrogenation of α,γ‐dienamido esters to γ,δ‐unsaturated amido esters has been achieved using Rh/TangPhos as the catalyst. A series of γ,δ‐unsaturated amido acids were furnished in excellent yields with up to 99 % ee. This effective methodology was applied in the asymmetric synthesis of key intermediate of Ramipril, an ACE inhibitor.     

Synthese der isomeren 3, 4-Dimethyl-4-phenyl-3, 4-dihydro-carbostyrile

Cyclisation of 2-methyl-3-phenyl-but-3-en-anilide (III) with polyphosphoric acid gave cis-3, 4-dimethyl-4-phenyl-3, 4-dihydro-carbostyril (VII) in 61% yield together with a small amount of 2, 3-dimethylindenone (VIII), whereas with AlCl₃ a phenyl group was split off to give 3, 4-dimethylcarbostyril (VI). The anilide III isomerises to cis- and trans-2, 3-dimethyl-cinnam-anilide (IV resp. V) under basic conditions. The anilides IV and V gave only small yields of the dihydrocarbostyril VII with polyphosphoric acid. Chlorination of VII in position 3 using PCl₅ yielded IX which, on splitting out HCl, gave 3-methylene-4-methyl-4-phenyl-3, 4-dihydro-carbostyril (X). X was converted to trans-3, 4-dimethyl-4-phenyl-3, 4-dihydro-carbostyril (XI) by catalytic hydrogenation.     

Tandem isomerization-lactonization of olefinic fatty acids using the Lewis acidic ionic liquid, choline chloride·2ZnCl2

The tandem isomerization-lactonization of unsaturated fatty acids to their corresponding γ-lactones was carried out for the first time in the presence of a Lewis acidic ionic liquid, choline chloride·2ZnCl₂. The ionic liquid initially catalyzes the stepwise migration of the double bond along the carbon chain toward the carboxyl group at the Δ4 position, which subsequently undergoes lactonization resulting in the formation of γ-lactones. This one step process allows the formation of γ-lactone in good yield with little or no formation of δ-lactones. The studied ionic liquid plays the dual role of solvent as well as catalyst.     

Synthesis of Alkenyl-Substituted Allenecarboxylates

The Wittig olefination of decanoyl chloride by using the phosphonium salt 1 in the presence of two equivalents of Et₃N represents a one-step synthesis of the racemic form of the naturally occurring pheromone (–)- 2 which contains an alkenyl-substituted allenic moiety (ef. Scheme 1). It is also shown, that unsaturated acyl chlorides which contain at least one γ-H-atom undergo the Wittig reaction with an appropriate phosphorane yielding γ-alkenyl-substituted α-allenic esters and α-allenic γ-lactones, respectively (ef. Schemes 2 and 3).     

Nitrene-Mediated Enantioselective Intramolecular Olefin Oxyamination to Access Chiral γ-Aminomethyl-γ-Lactones

Attaching a nitrene precursor to an intramolecular nucleophile allows for a catalytic asymmetric intramolecular oxyamination of alkenes in which the nucleophile adds in an endocyclic position and the amine in an exocyclic fashion. Using chiral-at-ruthenium catalysts, chiral γ-aminomethyl-γ-lactones containing a quaternary carbon in γ-position are provided in high yields (up to 99 %) and with excellent enantioselectivities (up to 99 % ee). DFT calculations support the possibility of both a singlet (concerted oxyamination of the alkene) and triplet pathway (stepwise oxyamination) for the formation of the predominant stereoisomer. γ-Aminomethyl-γ-lactones are versatile chiral building blocks and can be converted to other heterocycles such as δ-lactams, 2-oxazolidinones, and tetrahydrofurans.     

Oxidation of substituted 2-methyl benzoic acids and acrylic acids by S208  - ag(i); their conversion to phthalides and butenolides through rearrangement of acyloxyl radicals.

Ag (I) mediated persulphate oxidation of various 2-methyl benzoic acids and acrylic acids, co-catalyzed by Cu (II), leads to unsaturated γ-lactones, together with decarboxylation products. Lactonisation proceeds through 1,5 hydrogen transfer from intermediate acyloxyl radicals.     

Fluorolactonization of unsaturated carboxylic acids with F-TEDA-BF4 in ionic liquids

Fluorolactonization of unsaturated carboxylic acids under action of the electrophilic reagent F-TEDA-BF₄ in ionic liquids (ILs) has been studied. This reaction proceeds in ILs faster and provides a better stereoselectivity in comparison to acetonitrile as reaction media. Gem-difluorinated γ-lactones have been synthesized by interaction of unsaturated carboxylic acids with F-TEDA-BF₄ in ILs.     

Studies on the Alkaloids of Formosan Lauraceous Plants XVIII Alkaloids of Neolitsea Buisanensis Yamamoto Et Kamikoti and Neolitsea Aurata (Hay.) Koidz

Two alkaloids, laurolitsine (V) and litsericine (VII), were isolated from the woods of Neolitsea buisanersis. Six alkaloids were isolated from the woods of Neolitsea aurata and five of them were laurolitsine (V), litsericine (VII), N–methyllitsericine (VIII), (+)–anonaine (IX), and (–)-roemerine (X) (Table I).     

Asymmetric bromolactonization using amino-thiocarbamate catalyst

A novel amino-thiocarbamate-catalyzed bromolactonization of unsaturated carboxylic acids has been developed. The scope of the reaction is evidenced by 22 examples of γ-lactones with up to 99% yield and 93% ee. The protocol was applied in the enantioselective synthesis of the key intermediates of VLA-4 antagonists.     

Synthese des (R)-trans-11-Hydroxy-8-dodecensäure-lactons (Recieifeiolid)

Synthesis of Recifeiolide The synthesis of the mould metabolite recifeiolide (VIII), a 12-membered ring lactone, is described. 1,3-Butandiol was resolved with (?)-camphanic acid via (R)-1-iodo-3-butanol (II) into (R)-3-hydroxybutyl triphenyl phosphonium iodide (III). Wittig condensation of the phosphorane derived from III with methyl 8-oxo-octanoate (V) led to the methyl trans-11-hydroxy-8-dodecenoate (VI). The corresponding hydroxy acid VII was transformed into the S-(2-pyridyl) carbothioate which cyclizes under the influence of silver ion to the lactone VIII. With (?)-(R)-1,3-butandiol (I) as starting material the naturally occurring (+)-(R)-recifeiolide (VIII) is produced in 70% yield from VII.     

Stereoselective Synthesis of γ-(Acyloxy)carboxylic Acids and γ-Lactones Featuring the Switch of Stereopreference of Candida antarctica Lipase B in Sodium γ-Hydroxycarboxylate Homologues

Scalable protocols of straightforward synthesis of enantiomeric γ-(acyloxy)carboxylic acids and γ-lactones are presented. The key step is lipase-catalyzed stereoselective acylation of γ-hydroxycarboxylic acid sodium salt in organic solvent followed by acidification of the product, extraction and acidic relactonization of the unreacted enantiomer. The mixture of γ-(acyloxy)carboxylic acid and γ-lactone is separated either by extraction with solution of sodium bicarbonate or by distillation. A switch of enantioinduction of Candida antarctica lipase B along homologous nucleophiles from R configuration of γ-hydroxyhexanoic acid salt to S configuration of the C7 and longer-chain homologues has been disclosed. Both enantiomers of γ-(acyloxy)pentanoic acids; γ-(acetyloxy)octanoic and -nonanoic acids with S configuration; [(1S,5R)-5-(chloroacetyloxy)cyclopent-2-en-1-yl]acetic acid and enantiomeric γ-lactones derived from them were prepared with e. r. >98.5/1.5. The rates of acylation of C5 to C9 homologous salts differ by three orders of magnitude but remain applicable for preparative synthesis by variation of the enzyme loading and reaction time.     

Synthèse d'homologues de la (–)--(1R,2S)-norephedrine

Synthesis of (–)-(1R,2S)-Norephedrine Homologues The amino function of esters of some simple natural amino acids I is blocked in the form of a cyanoenamine by means of 2-oxocyclopentanecarbonitrile, so that the corresponding cyanoenamino esters II are obtained. The reaction of a disubstituted lithium amide with II leeds to the cyanoenamino-amides VI . The amide function present in VI is then transformed into an aromatic ketone by means of phenyllithium, to give the (benzoylalkyl)aminocyclopentenecarbonitriles VII . Reduction of Compounds VII with NaBH₄ in EtOH ?80° affects only the keto function and leads to the [(α-hydroxybenzyl)alkyl]amino-cyclopentenecarbonitriles VIII . The amino function is then deprotected by acid hydrolysis to give the amino-alcohols IX with yields close to 50%; in every amino-alcohol IX , the erythro isomer, homologous to natural (–)-(1R,2S)-norephedrine is the more abundant or the single product. All the polyfunctional compounds prepared conserve optical activity; it has been demonstrated that the amino-alcohols IX are pure enantiomers and that no racemisation lakes place at any step of their synthesis.     

Synthesis of γ-lactones from alkenes employing p-methoxybenzyl chloride as CH2---CO2 equivalent

The ZnCl₂ catalyzed reaction of p-methoxybenzyl chloride with alkenes yields the 1:1 addition products 3, which are converted into the γ-lactones 4 via Ru(VIII) catalyzed oxidative degradation of the aromatic ring.     

The first example of γ-chloromagnesio γ-lactones: their generation from γ-tolylsulfinyl γ-lactones with isopropylmagnesium chloride, stability, and reaction with electrophiles

The treatment of γ-lactones having a sulfinyl group at the γ-position, which were synthesized from 1-chlorovinyl p-tolyl sulfoxides with lithium enolate of carboxylic esters, with isopropyl magnesium chloride in THF at −78 °C gave γ-chloromagnesio γ-lactones by the sulfoxide-magnesium exchange reaction in high yields. The generated γ-chloromagnesio γ-lactones were found to be stable at below −50 °C for at least 2 h. The reaction of these γ-chloromagnesio γ-lactones with electrophiles and the stereochemistry of the reactions were investigated.     

Organocatalytic asymmetric 1,4-addition of organoboronic acids to γ-hydroxy α,β-unsaturated aldehyde: facile synthesis of chiral β-substituted γ-lactones

Catalytic asymmetric 1,4-addition of arylvinyl- and arylboronic acids to a γ-hydroxy α,β-unsaturated aldehyde, which affords β-substituted γ-lactols, has been established using a diarylprolinol silyl ether as an organocatalyst. The β-substituted γ-lactols have been obtained in good yields and with up to 91% ee, which lead to chiral β-substituted γ-lactones followed by oxidation.