Natural (−)‐Vasicine as a Novel Source of Optically Pure 1‐Benzylpyrrolidin‐3‐ol

A facile and scalable methodology for the preparation of optically active (3S)‐1‐benzylpyrrolidin‐3‐ol ( 3 ), an important drug precursor, is reported. Starting from the naturally occurring alkaloid (?)‐vasicine ( 1 ), a major alkaloid of the plant Adhatoda vasica, 3 was obtained in 84% overall yield (Scheme 3).     

Totalsynthese von natürlichem α-Tocopherol. 4. Mitteilung. Aufbau des Chromanringsystems aus Trimethylhydrochinon und einem optisch aktiven C4- bzw. C5-Synthon

Total Synthesis of Natural α-Tocopherol Two independent syntheses of (S)-6-hydroxy-2,5,7,8-tetramethylchroman-2-yl-methanol ( 8b ), (Scheme 6 resp. 9) as optically active chroman moiety for the preparation of natural vitamin E via (S)-6-acetoxy-2,5,7,8-tetramethylchroman-2-carboaldehyde ( 2a ) (Scheme 1) and a corresponding side chain are described. Both reaction sequences use trimethyl-hydroquinone as starting material; one approach employs an optically active C₄ unit ( 10a ) (Schemes 5 and 6) to introduce the required configuration at C(2), the other uses an optically active C₅-synthon ( 11a ) (Schemes 8 and 9) to build the optically active chroman unit. The correct configuration and optical purity of the chroman synthesized is established by correlation with optically pure material of known configuration from which natural vitamin E had already been derived [2].     

Stereoselective Syntheses of Tetrahydroesterastin-β -Lactam Analogues

A total synthesis of the optically active tetrahydroesterastin β -lactam analogue 2 using Miller's hydroxamate approach is described (Scheme 2). Significant modification of published procedures has resulted in a short and facile stereospecific preparation of the N-[(benzyloxycarbonyl)methyl]-β -lactam 17 starting from the readily available D -serine. This material served as intermediate for the preparation of a variety of N-[(benzyloxycarbonyl)methyl]tetrahydroesterastin β-lactam analogues (Scheme 5).     

Synthesis of Optically Active Bifunctional Isoprenoid Building Blocks by Rhodium(I)-Catalyzed Asymmetric Allylamine to Enamine Isomerization

The application of the known asymmetric allylamine to enamine isomerization methodology to bifunctional C⁵-isoprenoid allylic amines of types IId and IIe (Scheme 1) is described. It is shown that a number of such substrates can be isomerized with enantioselectivities of > 90% ee. using cationie Rh¹ complexes containing (6. 6′-dimethylbiphenyl′2, 2′-diyl)bis(dipheny phosphine) (BIPHEMP; 9) as asymmetry-inducing ligand (Scheme 2, Tables 1 and 2). Synthetically most useful is the isomerization of the benzyloxy derivative 10a into the (E)-enamine 11a . This isomerization proceeds with very high enantioselectivity (98-99% ee) and affords, after enamine hydrolysis, the optically active 4-(benzyloxy)-3-methylbutanals ((R)- or (S)- 12 ) in chemical yields of ca. 90%. In conjunction, a short synthetic route to the starting material 10a has been developed which has a Pd-catalyzed amination of isoprene epoxide ( 30 ) as the key step. Thus, convenient and practical access to the optically active aldehydes (R)-and (S)- 12 is now at hand. These aldehydes are useful optically active bifunctional building blocks for isoprenoid homologation.     

Straightforward and Facile Synthesis of a Bioactive Component from Zingiber cassumunar Roxb.

Straightforward and facile synthesis of a bioactive component A from Zingiber cassumunarRoxb. is described. The phenylbutenoid dimer A was reported to possess anti-inflammatory and cytotoxic activities. The optically active cyclohexene ring fragment was obtained via the highly diastereo- and enantioselective Diels–Alder reaction of chiral acryloyloxazolidinones (1a and 1b) and 1-(4-hydroxy-3-methoxyphenyl)butadiene (2). The enantiomeric excess of Diels–Alder adducts 3a and 3bwere determined via high-performance liquid chromatotography of the corresponding bis-acetate (6). The greatest enantiomeric excess (99.9% ee) was obtained when the 4-phenyloxazolidin-2-one (1a) chiral auxiliary was used in combination with TiCl4. The optically pure bioactive compound A was prepared from the optically active Diels–Alder adduct (3a) in two additional steps.     

Anisotropic derivatives of (-)-L-lactic acid and their nanocomposites

The paper describes the synthesis and physical-chemical properties of anisotropic derivatives of (-)-L-lactic acid and their nanocomposites. Anisotropic optically active aryl (S)-2-(ω-halogenalkoxy)lactates and (R)-2-aryloxypropionic acids have been synthesised by the modification of corresponding 3,6-disubstituted cyclohex-2-enones, (-) ethyl L-lactate and ethyl esters of (S)-2-(4-bromobutoxy)- and (S)-2-(6-bromohexyloxy)propionic acids. The optically active (R)-2-aryloxypropionic acids were used for the preparation of mesomorphic nanocomposite materials and their properties were studied. Anisotropic materials based on the derivatives of lactic acid are capable to interact with inorganic nanoparticles providing a tool for the creation of new nanocomposite materials.     

Synthesis of (R)- and (S)-5-(Hydroxymethyl)-3-isopropyloxazolidin-2-one,intermediates in the preparation of optically active β-blockers

The (R)- and (S)-5-(hydroxymethyl)-3-isopropyloxazolidin-2-ones, ((R)- and (S)- 2 , resp.), pivotal intermediates in the preparation of optically active β-blockers, were synthesized using (R,E)-2-hydroxypent-3-enenitrile ( 1 ) as the chiral starting material. In the synthesis of (R)- 2 , a known cyclization/inversion step was applied.     

Transition-Metal Free Electrophilic Aminations of Polyfunctional O-2,4,6-Trimethylbenzoyl Hydroxylamines with Zinc and Magnesium Organometallics

We reported a new electrophilic amination of various primary, secondary and tertiary alkyl, benzylic, allylic zinc and magnesium organometallics with O-2,4,6-trimethylbenzoyl hydroxylamines (O-TBHAs) in 52–99 % yield. These O-TBHAs displayed an excellent long-term stability and were readily prepared from various highly functionalized secondary amines via a convenient 3 step procedure. The amination reactions showed remarkable chemoselectivity proceeding without any transition-metal catalyst and were usually complete after 1–3 h reaction time at 25 °C. Furthermore, this electrophilic amination also provided access to enantioenriched tertiary amines (up to 88 % ee) by using optically enriched secondary alkylmagnesium reagents of the type s-AlkylMgCH₂SiMe₃.     

Synthesis of 4-azacyclopent-2-enones and 5,5-dialkyl-4-azacyclopent-2-enones

Three different methods are reported for the preparation of 4-azacyclo-2-enones 1, two of which allow the preparation of the compounds in optically active form. In addition, a facile route to 4-aza-5,5-dimethylcyclopent-2-enones 2 is disclosed.     

Optically active imidazole-containing polymers

In order to investigate the stereospecificity of enzyme-catalyzed reactions, an optically active copolymer of 4(5)-vinylimidazole and 2,5(S)-dimethyl-1-hepten-3-one was synthesized, and its effects on the solvolytic rates, in ethanol-water, of the p-nitrophenyl and 4-carboxy-2-nitrophenyl esters of 3(R)- and 3(S)-methylpentanoic acid and of the commercially available N-carbobenzoxy-(R)- and (S)-phenylalanine p-nitrophenyl esters were investigated. The optically active comonomer was prepared by thermal decomposition of solid (+)-1-piperidino-2,5(S)-dimethylheptan-3-one hydrochloride, which was obtained from the reaction of 2(S)-methylbutyllithium with 3-piperidino-2-methylpropionitrile. The 3(R)-methylpentanoic acid was prepared in 92% optical purity from L -alloisoleucine via diazotization in concentrated hydrobromic acid and subsequent reductive debromination with zinc amalgam in dilute hydrochloric acid. In the optically active copolymer-catalyzed solvolyses of the optically active esters performed at pH values of 6–8 no significant differences between the solvolytic rates of (R) and (S) isomers of substrates were observed. Poly-L -histidine was also employed as a catalyst for the solvolyses of these substrates. At pH 6.0 in ethanol–water the latter catalyst also failed to exhibit specificity towards (R) and (S) substrates.     

Optisch aktive C5-Bausteine zur Synthese von natürlich vorkommenden Terpenen

Optically Active C₅-Synthons for the Synthesis of Naturally Occurring Terpenes The optically active synthons (S)- 22 , (R)- 23 , (R)- 25 and (R)- 26 were prepared from L -serine. Furthermore the tertiary alcohol 6 was synthesized from L -serine (→(S)- 6 ) and D -mannitol (→(R)- 6 ). These compounds are suitable for the synthesis of optically active natural products.     

New Access to Sesquiterpene Hydroquinones: Synthesis of (+)‐ent‐Chromazonarol

A facile access to optically active (+)‐ent‐chromazonarol ent‐1, isolated from the sponge Disidea pallescens, is reported from commercially available (+)‐manool 4.     

Aromatic spiroketal bisphosphine ligands: palladium-catalyzed asymmetric allylic amination of racemic morita-baylis-hillman adducts

Showing a backbone: The spiroketal backbone of the bis(phosphine) ligand 1 led to good regio- and enantioselectivity in the palladium-catalyzed asymmetric allylic amination of racemic Morita-Baylis-Hillman adducts with aromatic amines. The methodology provides a facile and efficient synthesis of precursors for optically active β-lactam derivatives, including the cholesterol drug Ezetimibe.     

Synthesis of optically active 2,7-disubstituted naphthalene derivatives and evaluation of their enantioselective recognition ability

The palladium-catalyzed amination was used to synthesize 2,7-diamino derivatives of naphthalene containing two chiral substituents and fluorophore groups (dansyl, 7-methoxycoumarin, 6,7-dimethoxycoumarin, 6-aminoquinoline). The synthesized compounds were studied by UV absorption and fluorescence spectroscopy in the presence of individual enantiomers of amino alcohols and salts of 21 metals. The possibility of using these compounds as fluorescent detectors for optically active compounds and metals was examined. In the presence of (S)-leucinol, the diquinoline derivative showed enhanced emission with a maximum at shorter wavelengths, which is not typical of its (R) isomer. This fact can be used for the recognition of these enantiomers. A number of naphthalene derivatives can be considered as potential fluorescent chemosensors for Cu^II cations due to the total fluorescence quenching in the presence of this metal.

     

Synthesis and Sweetness of Pseddo-β-D and L-Frdctopyranose

Abstract

Pseudo-β-D (D-2) and L-fructopyranose (L-2), 1(S) and (1R)-(1,2/-3,4)-4-C-hydroxymethyl-1,2,3,4-cyclohexanetetrol, have been synthesized, starting from optically active endo-adducts of furan and acrylic acid, following the modified procedure used for the preparation of the racemic modification. It has been demonstrated that the D and L-enantiomers are nearly as sweet as D-fructose, and the former is somewhat sweeter than the latter.     

Catalytic intermolecular amination of C-H bonds: method development and mechanistic insights

Reaction methodology for intermolecular C-H amination of benzylic and 3 degrees C-H bonds is described. This process uses the starting alkane as the limiting reagent, gives optically pure tetrasubstituted amines through stereospecific insertion into enantiomeric 3 degrees centers, displays high chemoselectivity for benzylic oxidation, and enables the facile preparation of isotopically enriched 15N-labeled compounds. Access to substituted amines, amino alcohols, and diamines is thereby made possible in a single transformation. Important information relevant to understanding the initial steps in the catalytic cycle, reaction chemoselectivity, the nature of the active oxidant, and pathways for catalyst inactivation has been gained through mechanistic analysis; these studies are also presented.     

Investigation of the Chemo- and Stereoselectivity of the Ketene-Claisen Rearrangement

A novel type of ketene-Claisen rearrangement in which the precursor of the rearrangement is generated in situ by reaction of optically active allyl thioethers with dichloroketene is described. A characteristic feature of this rearrangement is the excellent chemoselectivity in favor of allyl thioethers vs. allyl ethers, i.e., exclusive chirality transfer of the allylic sulfur moiety is observed with 12, 13 , and 25--27 . The cyclic, optically active allyl thioethers (+)-(R)- 4 and (?)-(S)- 4 and the open-chain allyl thioethers 11--13 rearrange with in situ generated dichloroketene to the optically active thioesters (?)-(S)- 28 , (+)-(R)- 28 , and 31-33 , respectively. A chirality-transfer of > 99% in the cyclic cases (+)-(R)- 4 and (?)-(S)- 4 , and 96--98 % in the open-chain cases 11--13 is observed. Furthermore, the dichloroketene-Claisen rearrangement is characterized by a high asymmetric 1,2-induction. The chiral allylic sulfides 25--27 give the optically active thioesters 36--38 with a 1,2-induction > 99% as determined by NMR-shift experiments.     

Synthese von optisch aktiven,natürlichen Carotinoiden und strukturell verwandten Naturprodukten. VII. Synthese von (3R)-3-Hydroxyretinol, (3R)-3-Hydroxyretinal und (3R)-3-Hydroxyretinsäure

Synthesis of optically active natural carotenoids and structurally related compounds. VII. Synthesis of (3R)-3-hydroxyretinol, (3R)-3-hydroxyretinal and (3R)-3-hydroxyretinoic acid The synthesis of (3R)-3-hydroxyretinol, ( 7 ), (3R)-3-hydroxyretinal ( 9 ) and (3R)-3-hydroxyretinoic acid ( 5 ) according to the building principle C₁₅ + C₅ = C₂₀ is reported utilizing the optically active C₁₅-phosphonium salt 2 and the C₅-aldehyde ester 3 .     

Synthese und Chiralität von (5R, 6R)-5,6-Dihydro-β, ψ-carotin-5,6-diol, (5R, 6R, 6′R)-5,6-Dihydro-β, ε-carotin-5,6-diol, (5S, 6R)-5,6-Epoxy-5,6-dihydro-β, ψ-carotin und (5S, 6R, 6′R)-5,6-Epoxy-5,6-dihydro-β,ε-carotin

Synthesis and Chirality of (5R, 6R)-5,6-Dihydro-β, ψ-carotene-5,6-diol, (5R, 6R, 6′R)-5,6-Dihydro-β, ε-carotene-5,6-diol, (5S, 6R)-5,6-Epoxy-5,6-dihydro-β,ψ-carotene and (5S, 6R, 6′R)-5,6-Epoxy-5,6-dihydro-β,ε-carotene Wittig-condensation of optically active azafrinal ( 1 ) with the phosphoranes 3 and 6 derived from all-(E)-ψ-ionol ( 2 ) and (+)-(R)-α-ionol ( 5 ) leads to the crystalline and optically active carotenoid diols 4 and 7 , respectively. The latter behave much more like carotene hydrocarbons despite the presence of two hydroxylfunctions. Conversion to the optically active epoxides 8 and 9 , respectively, is smoothly achieved by reaction with the sulfurane reagent of Martin [3]. These syntheses establish the absolute configurations of the title compounds since that of azafrin is known [2].     

Totalsynthese von natürlichem α-Tocopherol. 2. Mitteilung. Aufbau der Seitenkette aus (−)-(S)-3-Methyl-γ-butyrolacton

Total Synthesis of Natural α-Tocopherol A short and efficient route to optically pure (+)-(3 R, 7 R)-trimethyldodecanol ( 14 ) is demonstrated, 14 serving as side chain unit in the preparation of natural vitamin E. The synthesis of 14 is based on the concept of using a single optically active C₅-synthon of suitable configuration and functionalization to introduce both asymmetric centres in 14 . (?)-(S)-3-Methyl-γ-butyrolacton ( 1 ) and ethyl (?)-(S)-4-bromo-3-methylbutyrate ( 2 ), respectively, is used in a sequence of either two Grignard C,C-coupling reactions 5 → 8 and 12 → 13 or two Wittig reactions 17a → 18 and 20 → 21 to achieve this goal. 14 is converted to (2 R, 4′R, 8′R)-α-tocopherol (= vitamin E) by coupling with a chroman unit in known manner. Optical purity of products and intermediates is established.