Search

Five Jasminum grandiflorum flower absolutes harvested as flower buds and processed in the “ J. sambac-way” in different locations in the southern Indian state of Tamil Nadu were analyzed using gas chromatography (GC) and GC-mass spectrometry. These absolutes were compared with 5 commercial Indian J. grandiflorum flower absolutes manufactured in the traditional “ J. grandiflorum-way” from open flowers. Focus was placed on 42 key ingredients to investigate the influence of such a flower processing on the absolute composition. Our study established olfactive and composition differences of such absolutes produced via the “ J. sambac-way.” In addition, geographic variations in this species were analyzed by comparing 5 commercial Indian J. grandiflorum flower absolutes with absolutes from Egypt and Morocco, respectively. A composition range of the absolutes was established for the 3 main J. grandiflorum flower grower countries using a total of 14 commercial samples. The 12 main ingredients in the absolutes showed variations between 4.3% and 89.7%.

Purpose To study immunogenic properties of human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) and to evaluate subretinal xenotransplantation of hESC-RPE on porous polyethylene terephthalate (PET) in rabbits. Methods Human ESC-RPE cells were characterized by morphology, transepithelial electrical resistance (TER), protein expression and photoreceptor outer segment phagocytosis in vitro. Expression of major histocompatibility complex (MHC) proteins was assessed in conventionally or xeno-free produced hESC-RPE ± interferon-gamma (IFN-γ) stimulation (n = 1). Xeno-free hESC-RPE on PET with TER or PET alone were transplanted into 18 rabbits with short-term triamcinolone ± extended tacrolimus immunosuppression. Rabbits were monitored by spectral domain optical coherence tomography. After 4 weeks, the eyes were processed for histology and transmission electron microscopy. Results Upon in vitro IFN-γ stimulation, xeno-free hESC-RPE expressed lower level of MHC-II proteins compared to the conventional cells. Outer nuclear layer (ONL) atrophy was observed over the graft in most cases 4 weeks post-transplantation. In 3/4 animals with high TER hESC-RPE, but only in 1/3 animals with low TER hESC-RPE, ONL atrophy was observed already within 1 week. Retinal cell infiltrations were more frequent in animals with high TER hESC-RPE. However, the difference was not statistically significant. In three animals, preservation of ONL was observed. Weekly intravitreal tacrolimus did not affect ONL preservation. In all animals, hESC-RPE cells survived for 4 weeks, but without tacrolimus, enlarged vacuoles accumulated in hESC-RPE (n = 1). Conclusions Xenografted xeno-free hESC-RPE monolayers can survive and retain some functionality for 4 weeks following short-term immunosuppression. The preliminary findings of this study suggest that further investigations to improve transplantation success of hESC-RPE xenografts in rabbits should be addressed especially toward the roles of hESC-RPE maturation stage and extended intravitreal immunosuppression.

Two Chinese black cardamom oils ( Amomum tsao-ko) were analyzed using GC and GC/MS and compared to 2 Indian cardamom oils from the species Amomum subulatum and Elettaria cardamomum, respectively. The main constituents of A. tsao-ko oils were eucalyptol, geranial, geraniol, trans-2,3,3A,7A-tetrahydro-1 H-indene-4-carbaldehyde, (2 E)-decenal, neral, and 4-indanecarbaldehyde. Special attention was given to the 1 H-indene-carbaldehyes, which are frequently wrongly assigned in previous literature. A detailed odor evaluation of the oils was also carried out. In addition, composition variations of 28 main constituents of 8 E. cardamomum oils were investigated, taking various factors like origin, production methods, plant material, and drying stage into consideration.

This contribution reviews a family of reactions devised in our laboratory that effect the oxidative conversion of phenols into 4-amido-dienones. A salient feature of this chemistry is the use of hypervalent iodine reagents, especially diacetoxyiodobenzene (DIB), as uniquely capable oxidants in the context of the new transformation. The advent of this methodology has created new opportunities in alkaloid synthesis. Our efforts toward FR-901483, TAN-1251C, cylindricine C, and other nitrogenous natural products illustrate some applications in that domain. 1 Introduction 2 Background 3 First-Generation Oxidative Amidation of Phenols: The Oxazoline Route 4 Initial Applications: Total Synthesis of FR-901483 and of TAN-1251C 5 Second-Generation Oxidative Amidation of Phenols: Sulfonamide Technology 6 Applications: Total Synthesis of (-)-Cylindricine C 7 Third-Generation Solution: The Bimolecular Reaction 8 Conclusion

Four commercial qualities of Hawaiian sandalwood oil produced from wood of Santalum paniculatum originating from the island of Hawaii ("The Big Island") were analyzed using GC and GC-MS. Main constituents of the oils were (Z)-α-santalol (34.5-40.4%) and (Z)-β-santalol (11.0-16.2%). An odor evaluation of the oils was carried out against East Indian sandalwood oil. In addition, the chemical composition of Hawaiian sandalwood oil was compared with four different Santalum species originating from East India, New Caledonia, Eastern Polynesia and Australia, respectively.

(Z/E)-β-Curcumen-12-ol (Z/E)-(1) was synthesized via Birch reduction of acid 6 starting from αcurcumene (5). An olefin isomerization of 1 is the key step in the synthesis of (Z/E)-γ-curcumen12-ol (Z/E)-(2). Sesquiterpene alcohol (E)-1 was found for the first time in nature as a minor constituent of different Santalum species by using the synthetic sample as reference.

We describe the development of a technique for the oxidative conversion of 4-alkyl phenols to derivatives of the corresponding 4-alkyl-4-amino-2,5-cyclohexanediones. This transformation, which was inspired by biogenetic considerations, constitutes a key step in the total syntheses of FR-901483, TAN-1251C, and cylindricine C.

Three qualities of New Caledonian sandalwood oil were analyzed using GC and GC/MS. Eighty-four constituents were identified: 10 monoterpenes, 72 sesquiterpenes and two others. In addition β-bisabolol/epi-β-bisabolol isomers were isolated and characterized via chiral GC chromatography. Our results indicate that New Caledonian sandalwood oil is much closer related to East Indian sandalwood oil than its Western Australian counterpart.

Reaction of C-2 substituted cyclohexenone with an enantiomerically pure α-bromopentenoate leads to enantiopure tricyclooctane, which can be transformed into a taxoid like compound having the typical bicyclo[5.3.1]undecane skeleton.

The 3-methyl-4-(tricyclo[5.2.1.02,6]dec-4-en-8-ylidene)butan-2-ols (=Fleursandol®; rac-10), a new class of sandalwood odorants, were synthesized in their enantiomerically pure forms by use of tricyclo[5.2.1.02,6]dec-4-en-8-ones 17 and ent-17 and (tetrahydro-2H-pyran-2-yl)-protected 4-bromo-3-methylbutan-2-ols 22 and ent-22 as starting materials (Schemes 2–4). Only four of 16 possible stereoisomers of rac-10 possess the typical, very pleasant, long-lasting sandalwood odor (Table 1). The (2S,3R,4E,1′R,2′R,6′R,7′R)-isomer ent-10a is by far the most important representative, with an odor threshold of 5 μg/l in H2O.

Six stereoisomers of nor-helifolen-12-al and four isomers of acoren-11-ol (α-acorenol, epi-α-acorenol, β-acorenol, epi-β-acorenol) were identified for the first time in Australian sandalwood oil.

The odorous trace constituent iso-β-bisabolol (4) was isolated from East Indian and Western Australian sandalwood oil and synthesized by using the (E/Z)-triene 12 (iso-γ-bisabolene) as a key intermediate. Only one of four stereoisomeric forms of 4, (6R,7R)-4a, is odor active, having a strong floral, muguet-like, very pleasant scent.

The stem wood oil of Vanillosmopsis erythropappa Schultz-Bip. was analyzed using GC/MS. Forty-three constituents were identified: 31 sesquiterpenoids, one phenylpropane and 11 others. 2-Bisabolene-7, 11-diol and 10-bisabolene-3,7-diol were found for the first time in nature and were characterized using 1H-, 13C-NMR, GC/FTIR and GC/MS analyses.

Commercial Australian sandalwood oil produced from Santalum spicatum (R. Br.) A. DC. roots was analyzed using GC and GC/MS. Seventy constituents were identified: four monoterpenes, 64 sesquiterpenes and two others. Four compounds (Z)-β-curcumen-12-ol, (Z)-12-hydroxysesquicineole,6,10-epoxybisabol-2-en-12-olandnor-helifolen-12-al were found to our knowledge for die first time in nature and were characterized using 1H-, 13C-N M R, GC/FTIR and GC/MS analyses.

A solution to the long-standing problem presented by the oxidative cyclization of a phenolic 3-arylpropionamide to a spirolactam has been developed in this laboratory via oxazoline chemistry. This research was motivated by our interest in some novel tricyclic azaspirane natural products formally derived from tyrosine, such as FR901483 and TAN1251C. In this paper, we disclose full details of the total synthesis of these substances.

An anionically induced domino reaction is the key step in the synthesis of the isotwistane skeleton. This precursor can be transformed into the marine sesquiterpene 2-isocyanopupukeanane or its structural analogues.

The oxidative cyclization of a phenolic amide to a spirolactam has long been regarded as an "impossible" reaction, because exposure of the substrates to a variety of oxidants results in formation of spirolactones with consequent loss of the amine segment. We recently communicated that this heretofore unknown transformation may be achieved by oxidation of oxazoline analogues of phenolic and indolic amides. Herein, we provide full details of our work.

The chiral α-bromo α,β-unsaturated esters 3 and 9 are prepared by asymmetric Sharpless dihydroxylation (AD) of 5 and from ester 7 and the chiral diols 8 by transacetalization, respectively. Both types of α-bromo α,β-unsaturated ester react with the kinetic lithium dienolates of enone 10 to give functionalized tricyclo[3.2.1.02,7]octanes 11. Esters 3 give one single diastereomer (de ≥ 95%), whereas mixtures of diastereomers (de 28 to 46%) are obtained with the esters 9.

Oxidation of oxazolines derived from phenolic ω-arylalkanoic acids such as tyrosine with iodobenzene diacetate leads to spirocyclic amides in moderate yields. This reaction was heretofore unknown due to the propensity of free amide analogs of the oxazolines to furnish lactones upon oxidation.

Layer-by-layer assembled shells are prospective candidates for encapsulation, stabilization, storage, and release of fragrances. A shell comprising four alternative layers of a protein and a polyphenol is employed to encapsulate the dispersed phase of a fragrance-containing oil-in-water emulsion. The model fragrance used in this work consists of 10 ingredients, covering a range of typically employed aroma molecules, all premixed in equal mass and with sunflower oil acting as the base. The encapsulated emulsion is stable after 2 months of storage at 4 °C as revealed by static light scattering and confocal laser scanning microscopy. Gas chromatography/mass spectrometry data show that the encapsulation efficiency of 8 out of 10 fragrance ingredients depends on the water solubility: the less water-soluble an ingredient, the more of it is encapsulated. The amount of these fragrance ingredients remaining encapsulated decreases linearly upon emulsion incubation at 40 °C and the multilayer shell does not hinder their release. The other two fragrance ingredients having the lowest saturation vapor pressure demonstrate sustained release over 5 days of incubation at 40 °C. The composition of released fragrance remains almost constant over 3 days of incubation, upon further incubation it becomes enriched with these two ingredients when others start to be depleted.

Starting from the easily accesible chiral aldehyde 2, we obtained enantiomerically pure (Z)- and (E)-α,-chloro-α,β-unsaturated esters 4c in good yields by olefination reactions. (Z)-and (E)-4c were allowed to react with the kinetically controlled generated lithium dienolate Li-7 to give the enantiomerically pure tricyclo[3.2.1.02,7]octanes 8 and 9, respectively. The „push-pull” substituted cyclopropane moiety of 8 was opened to give solely bicyclo[3.2.1]octane 10.

One pot cascade reactions of 3-benzyloxy-cyclohex-2-enone (1) with tert-butyl-(Z)-(+)-2-chloro-3-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-propenoate (2) lead to (1S;2R;5S;7S;8R;4′S)-tert-butyl-2-benzyloxy-8-(2′,2′-dimethyl-1′,3′-dioxolan-4′-yl)-6-oxo-tricyclo[3.2.1.02,7]octane-1- carboxylate (3) and with (E)-(+)-2 to (1R;2S;5R;7R;8S;4′S)-4. The tricyclic compounds 3 and 4 were formed with high diastereomeric excess.

Purpose We developed a surgical method for localized and atraumatic removal of the retinal pigment epithelium (RPE) with a novel instrument. Methods Bleb retinal detachments (bRD) were raised with balanced salt solution (BSS) following vitrectomy in 27 rabbits. The RPE was scraped with 3 loop variants (polypropylene [PP], 0.1 mm; PP, 0.06 mm; metal, 0.1 mm) of a custom-made instrument. Stabilization of bRDs with BSS or various concentrations (0.1%–0.5%) of hyaluronic acid (HA) was video analyzed. Perfusion-fixed samples of scraped areas and controls were studied by light and transmission electron microscopy. Results The bRDs were sufficiently stabilized by ≥0.25% HA. Using the PP 0.1 mm loop with a single forward/backward stroke, an area of ca. 2.5 × 1.5 mm was nearly devoid of RPE, yet did show occasional Bruch's membrane (BM) defects combined with choriocapillaris hemorrhages in 13% of the bRDs. A single scrape with PP 0.06 mm resulted in unsatisfactory RPE denudement, while repeated scraping maneuvers caused more BM defects and hemorrhages. The metal loop resulted in incomplete RPE removal and massive intraoperative subretinal hemorrhages. Histologically, intact photoreceptor outer segments (POS) were observed above the RPE wounds in bRDs. Controls with bRDs alone showed an intact RPE monolayer with microvilli, with few engulfed remains of POS. Conclusions Localized removal of RPE in HA stabilized bRD can be achieved by a PP 0.1 mm loop instrument. Translational Relevance Removal of degenerated RPE may aid RPE cell replacement strategies.

The essential oil produced from the heartwood of Santalum album L. was analyzed using GC/MS. Forty-four constituents were identified: one monoterpene and 43 sesquiterpenes. 2,10-Bisaboladien-6-ol (= β-bisabolol/epi-β-bisabolol) was one of the trace compounds found in east Indian sandalwood oil. Chiral GC analysis showed that besides the main stereoisomer, which possessed an (R,R)-configuration, all three other isomers were also present.

The essential oil of Aquilaria agallocha Roxb. was analyzed using GC/MS. The main constituents were found to be agarospirol (12.1%) and jinkoh-eremol (10.0%). Anisyl acetone was isolated as a minor constituent and fully characterized from a commercial sample of agarwood oil.

Seven Jasminum sambac flower absolutes from different locations in the southern Indian state of Tamil Nadu were analyzed using GC and GC-MS. Focus was placed on 41 key ingredients to investigate geographic variations in this species. These seven absolutes were compared with an Indian bud absolute and commercially available J. sambac flower absolutes from India and China. All absolutes showed broad variations for the 10 main ingredients between 8% and 96%. In addition, the odor of Indian and Chinese J. sambac flower absolutes were assessed.

The essential leaf oil of Laurus nobilis L. was analyzed using GC/MS. One hundred and fifty-five constituents were identified: 76 monoterpenoids, 46 sequiterpenoids, 10 phenylpropanoids and 23 others. 8-Terpinyl acetate was found to our knowledge for the first time in nature and was characterized using 1H-, 13C-NMR, GC/FTIR and GC/MS analysis.

One pot cascade reactions of 3-benzyloxy-cyclohex-2-enone (1) with tert-butyl-(Z)-(+)-2-chloro-3-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-propenoate (2) lead to (1S;2R;5S;7S;8R;4′S)-tert-butyl-2-benzyloxy-8-(2′,2′-dimethyl-1′,3′-dioxolan-4′-yl)-6-oxo-tricyclo[3.2.1.02,7]octane-1- carboxylate (3) and with (E)-(+)-2 to (1R;2S;5R;7R;8S;4′S)-4. The tricyclic compounds 3 and 4 were formed with high diastereomeric excess.

Starting from the easily accesible chiral aldehyde 2, we obtained enantiomerically pure (Z)- and (E)-α,-chloro-α,β-unsaturated esters 4c in good yields by olefination reactions. (Z)-and (E)-4c were allowed to react with the kinetically controlled generated lithium dienolate Li-7 to give the enantiomerically pure tricyclo[3.2.1.02,7]octanes 8 and 9, respectively. The „push-pull” substituted cyclopropane moiety of 8 was opened to give solely bicyclo[3.2.1]octane 10.

Baeyer-Villiger oxidation of 3 gives solely the lactones 4 . The double-pull-push substituted cyclopropane moiety of 4b is selectively opened upon hydrogenolysis of the benzyl ether to yield ketone 5 .

A novel oxidation of indolic 2-oxazolines with iodobenzene diacetate leads to unusual spiroheterocycles of potential interest in synthetic and medicinal chemistry. In several instances, addition of 2,2,2-trifluoroethanol (the solvent for such oxidations) to the substrates was observed.

This contribution reviews a family of reactions devised in our laboratory that effect the oxidative conversion of phenols into 4-amido-dienones. A salient feature of this chemistry is the use of hypervalent iodine reagents, especially diacetoxyiodobenzene (DIB), as uniquely capable oxidants in the context of the new transformation. The advent of this methodology has created new opportunities in alkaloid synthesis. Our efforts toward FR-901483, TAN-1251C, cylindricine C, and other nitrogenous natural products illustrate some applications in that domain. 1 Introduction 2 Background 3 First-Generation Oxidative Amidation of Phenols: The Oxazoline Route 4 Initial Applications: Total Synthesis of FR-901483 and of TAN-1251C 5 Second-Generation Oxidative Amidation of Phenols: Sulfonamide Technology 6 Applications: Total Synthesis of (-)-Cylindricine C 7 Third-Generation Solution: The Bimolecular Reaction 8 Conclusion

Four commercial qualities of Hawaiian sandalwood oil produced from wood of Santalum paniculatum originating from the island of Hawaii (“The Big Island”) were analyzed using GC and GC-MS. Main constituents of the oils were ( Z)-α-santalol (34.5–40.4%) and ( Z)-β-santalol (11.0–16.2%). An odor evaluation of the oils was carried out against East Indian sandalwood oil. In addition, the chemical composition of Hawaiian sandalwood oil was compared with four different Santalum species originating from East India, New Caledonia, Eastern Polynesia and Australia, respectively.

[structure: see text]. The total synthesis of FR901483, a structurally novel immunosuppressant, has been accomplished by the use of technology recently developed in this laboratory for the oxidative cyclization of phenolic oxazolines to spirolactams. Our approach may reflect the biosynthetic pathway leading to the natural product.

The oxidative cyclization of a phenolic amide to a spirolactam has long been regarded as an “impossible” reaction, because exposure of the substrates to a variety of oxidants results in formation of spirolactones with consequent loss of the amine segment. We recently communicated that this heretofore unknown transformation may be achieved by oxidation of oxazoline analogues of phenolic and indolic amides. Herein, we provide full details of our work.

Seven Jasminum sambac flower absolutes from different locations in the southern Indian state of Tamil Nadu were analyzed using GC and GC-MS. Focus was placed on 41 key ingredients to investigate geographic variations in this species. These seven absolutes were compared with an Indian bud absolute and commercially available J. sambac flower absolutes from India and China. All absolutes showed broad variations for the 10 main ingredients between 8% and 96%. In addition, the odor of Indian and Chinese J. sambac flower absolutes were assessed.

Purpose To develop a surgical technique for the subretinal implantation of cell carriers suitable for the transplantation of cultured retinal pigment epithelium (RPE) in a preclinical animal model. Methods Cell carriers were porous 10-μm-thick polyester membranes. A custom-made shooter instrument consisted of a 20-gauge metallic nozzle with a nonstick plunger. Fetal human RPE cultures were used for vitality assessment during instrument handling. Transvitreal subretinal implantation of carriers without RPE was performed in 31 rabbits after vitrectomy. Fourteen of 31 implants were encapsulated in gelatin. Fluid turbulence over the implantation site was minimized using a novel infusion cannula. Six rabbits had intravitreal plasmin injections before surgery. SD-OCT in vivo images were obtained after 3, 7, and 14 days, followed by perfusion-fixed histology. Results Gelatin encapsulation of RPE/polyester implants made cell loss during handling reproducible, compared with 40% of controls showing random, large damage zones. Gelatin implants were ejected smoothly in 12 of 14 surgeries (86%), whereas "naked" implants frequently became trapped with the instrument, which reduced success to 9 of 17 cases (53%). Vitreous remnants after vitrectomy alone complicated subretinal placement of encapsulated and naked implants in 7 of 25 cases (28%). Plasmin-assisted vitrectomy resulted in implant ejection unperturbed by vitreous adhesions in six experiments. SD-OCT and histology demonstrated atraumatic subretinal implant delivery after uncomplicated surgery. Conclusions A novel shooter instrument design allows for safe and atraumatic transvitreal delivery of hydrogel-encapsulated, ultrathin, rigid-elastic carriers into the subretinal space. The procedure may be used in the future to deliver cultured RPE.

Jasminum flexile flower absolute from the south of India and the corresponding vacuum, headspace (VHS) sample of the absolute were analyzed using GC and GC-MS. Three other commercially available Indian jasmine absolutes from the species: J. sambac, J. officinale subsp. grandiflorum, and J. auriculatum and the respective VHS samples were used for comparison purposes. One hundred and twenty-one compounds were characterized in J. flexile flower absolute, with methyl linolate, benzyl salicylate, benzyl benzoate, (2E,6E)-farnesol, and benzyl acetate as the main constituents. A detailed olfactory evaluation was also performed.

Three qualities of Eastern Polynesian sandalwood oil were analyzed using GC and GC-MS. Sixty-six constituents were identified: 5 monoterpenes, 58 sesquiterpenes and 3 others. The main constituents of the essential oils were ( Z)-α-santalol and ( Z)-β-santalol. Beside chemical composition, olfactory evaluation and chiral gas chromatography of β- and epi-β-bisabolol isomers confirmed the close relationship of Eastern Polynesian to East Indian and New Caledonian sandalwood oil.

Wittig olefination of the aldehydes 2a/b gave the 2-bromo-dienes 3a/b . Regioselective catalytic Sharpless asymmetric dihydroxylation (AD) led to the diols 4a/b with high enantiomeric excess (ee > 94 %). Cascade reactions of 5a/b with dienolate 6 yielded 7a/b with excellent diastereomeric excess (de > 95 %).

Baeyer-Villiger oxidation of 3 gives solely the lactones 4 . The double-pull-push substituted cyclopropane moiety of 4b is selectively opened upon hydrogenolysis of the benzyl ether to yield ketone 5 .