Academic literature on the topic '8ol-1(dimethyl-3,9 isopropyl-6)acetate'

The analytical result by 80°С-based TD-GC/MS showed that 65 peaks were obtained from the helium volatiles from the fresh branches of Cinnamomum camphora and 60 chemical compounds were identified. The results showed that the main components were as: 1,3-Benzodioxole, 5-(2-propenyl)- (12.629%), Tricyclo[2.2.1.0(2,6)]heptane, 1,7-dimethyl-7-(4-methyl-3-pentenyl)-, (-)- (10.302%), 3-Cyclohexene-1-methanol, .alpha.,.alpha.4-trimethyl- (9.084%), Bicyclo[2.2.1] heptan-2-one, 1,7,7-trimethyl-, (1R)- (7.406%), Nerolidol (6.695%), Bicyclo[2.2.1]heptane, 2-methyl-3-methylene-2-(4-methyl-3-pentenyl)-, (1S-exo)- (6.017%), Bicyclo[2.2.1]heptan-2-one, 1,7,7-trimethyl-, (.+/-.)- (4.885%), Bicyclo[3.1.1]hept-2-ene, 2,6-dimethyl-6-(4-methyl-3-pentenyl)- (4.680%), Naphthalene, 1,2,3,5,6,8a-hexahydro-4,7-dimethyl-1-(1-methylethyl)-, (1S-cis)- (4.139%), 3-Cyclohexen-1-ol, 4-methyl-1-(1-methylethyl)-, (R)- (3.538%), Copaene (2.749%), Bicyclo[2.2.1] heptan-2-ol, 1,7,7-trimethyl-, (1S-endo)- (2.643%), Acetic acid, 1,7,7-trimethyl-bicyclo [2.2.1]hept-2-yl ester (2.536%), Cyclohexane, bromo- (2.530%), 1,6,10-Dodecatriene, 7,11- dimethyl-3-methylene-, (E)- (1.725%), Naphthalene, 1,2,3,4,4a,5,6,8a-octahydro-7-methyl-4- methylene-1-(1-methylethyl)-, (1.alpha.,4a.beta.,8a.alpha.)- (1.265%), Bicyclo[4.4.0]dec-1-ene, 2-isopropyl-5-methyl-9-methylene- (1.174%), (-)-Isosativene (1.149%), 11-Tetradecen-1-ol acetate (1.118%), .alpha.-Cadinol (1.061%), etc. The analytical result suggested that the helium volatiles from the fresh branches of C. camphora could be used as industrial materials of biomedicines, spicery and food industry.

The seedlings of Oroxylum indicum were inoculated with plant growth promoting microbes (PGPMs) mainly, Glomus mosseae, Trichoderma harzianum and Pseudomonas putida both alone and consortium. The GCMS analysis of the methanolic root extract of inoculated seedlings of O. indicum showed that seedlings treated with mixed consortium of mycorrhizal fungi, bacteria and fungus showed the presence of maximum number of phytocompounds. The GC-MS analysis of control seedlings showed presence of 55 compounds where three new compounds were found i.e. 2-Cyclobutene-1-Carboxamide; Tetradecanoic Acid, 10, 13-dimethyl-, methyl ester; 1-methylene-2b-hydroxymethyl-3, 3-dimethyl-4b-(3-methylbut-2-enyl)-cy. 53 compounds were found in seedlings treated with mycorrhizae i.e., Glomus mosseae, and three new compounds were found i.e., 1-Ethyl-2-Hydroxymethylimidazole; Octadecanoic Acid, 11-Methyl-, methyl ester; 4-Methyl-1, 4-Heptadiene. The seedlings treated with bacteria i.e. Pseudomonas putida showed the presence of 52 compounds and three new compounds were found i.e. Meso-4, 5-octanediol; 1-ethyl-2-hydroxymethylimidazole; 2, 5-cyclohexadiene-1, 4-dione, 2, 5-dihydroxy-3-methyl-6-(1-methylethyl) - . A total of 56 compounds were present in seedlings treated with fungus i.e. Trichoderma harzianum and five new compounds were found i.e. 2-CyclohexeN-1-one, 2-Butyl-3-Methoxy; Methyl 12, 13-Tetradecadienoate; Methyl 6, 9, 12-hexadecatrienoate; 1, 9-Decadiyne; 1, 4-Naphthalenedione. The seedlings treated with dual consortium of mycorrhizae and bacteria showed the presence of 88 compounds and five new compounds were found i.e., N-(1-Methoxycarbonyl-1-methylethyl)-4-methyl-2-aza-1,3-dioxane;1-ethyl-2 hydroxy methylimidazole; Methyl 8-methyl-nonanoate; Naphthalene, 1,2,3,4,4a,5,6,8a-octahydro-4a,8-dimethyl; Methyl 12,13-tetradecadienoate. 152 compounds were present in seedlings treated with dual consortium of mycorrhizal fungi and fungus and ten new compounds were found to be present i.e. 1,9-Decadiyne; 3,7,11-Trimethyl-3-hydroxy-6,10-dodecadien-1-yl acetate; 3-Heptyne, 7-chloro; 3-Methyl-4-(methoxycarbonyl) hexa-2,4-dienoic acid; Benzo[c]cinnolin-2-amine ; Tetradecanoic acid, 10,13-dimethyl-,Methyl ester; Cis,cis-4,6-octadienol; 2-Cyclohexen-1-one, 2-butyl-3-methoxy; Methyl 12,13-tetradecadienoate; 2-Aminopyridazino(6,1-b) quinazolin-10-one. A total of 36 compounds were present in seedlings treated with dual consortium of bacteria and fungi and two new compounds were found i.e. [1,4] Dioxino [2,3-b]-1,4-dioxin, hexahydro-2,3,6,7 ; 1-Ethyl-2-hydroxymethylimidazole. The seedlings inoculated with mixed consortium of mycorrhizae, bacteria and fungus showed the presence of 213 compounds and fourteen new compounds were found i.e. 3,7,11-Tridecatrienenitrile, 4,8,12-Trimethyl; 1,9-Decadiyne; 2,6,10,14,18,22-Tetracosahexaene, 2,6,10,15,19,23-Hexamethyl-, (ALL-E) ; 1-Methylene-2b-hydroxymethyl-3,3-dimethyl-4b-(3-methylbut-2-enyl)-cy; 1,9-Decadiyne, Cyclobutane, 1,2-bis(1-methylethenyl)-, trans-, 3,7,11-Trimethyl-3-hydroxy-6,10-dodecadien-1-yl acetate, 5-Hydroxy-4-hydroxymethyl-1-(1-hydroxy-1-isopropyl)cyclohex-3-ene, 5,8,11,14-Eicosatetraenoic acid, methyl ester, (all-z)-, 1-Cyclohexyl-2-buten-1-ol (c,t) , 1-Oxetan-2-one, 4,4-diethyl-3-methylene-, Tetradecanoic acid, 10,13-dimethyl-, methyl ester, 2-Cyclohexen-1-one, 2-butyl-3-methoxy-, Methyl 12,13-tetradecadienoate, Heptacosanoic acid, 25-methyl-, methyl ester Hexadecanoic Acid, Methyl Ester; 2-Chloroethyl Linoleate; 9,12-Octadecadienoic Acid, Methyl Ester, (E,E); Butanoic acid, methyl ester; 4A,5,6,7,8,8A(4H) HexahydroBenzopyran-3-Carboxamide, 8A-Methoxy-4A-M,; Octadecanoic acid; Farnesene; Squalene; Myrcene; Naphthalene; Tetradecanoic Acid, Methyl Ester; Octadecanoic Acid, Methyl Ester; 1H-Cycloprop[E] Azulene, Decahydro-1,1,4,7-Tetramethyl-, [1AR-(1A].Alph ; Cyclohexane, 1-methyl-4-(1-methylethenyl)-, trans (Elemene); Cyclohexene, 1-methyl-4-(1-methylethenyl)-, (s)- (Limonene); were found to be present in this treatment.

A facile procedure for the preparation of 6-aryl-1,3-dimethyl-5H-pyrimido[4,5-b][1,4]diazepine2,4(1H,3H)-diones 8, 9 from 6-amino-5-arylideneamino-1,3-dimethyluracils 1, 2 and triethyl orthoacetate (3) in a two-step reaction via 6-aryl-8-ethoxy-6,7-dihydro-1,3-dimethyl-5H-pyrimido[4,5-b][1,4]diazepine-2,4(1H,3H)-diones 6, 7 is described. Condensation of 1 with diethoxymethyl acetate (10) resulted in the formation of (1,3-dimethyl-2,6-(1H,3H)-dioxopurin-7-yl)(phenyl)methyl acetate (11) and a small amount of 1,3-dimethyl-6-phenylpyrazino[2,3-d]pyrimidine-2,4(1H,3H)-dione (12). The structures of 6 and 11 were unambiguously confirmed by single-crystal X-ray diffraction analysis.

The aim of this project was to attempt to find a method for introducing the cis-dihydroxyl substitution at the A/B-ring junction of model compounds related to the saquayamycins. The Diels-Alder reactions of maleic anhydride and bromomaleic anhydride with 5,5-dimethyl-3-vinylcyclohexa-1,2-dienyl acetate gave the two required endo-adducts in good yield, namely (octahydrobenzo[e]isobenzofuran-9-yl acetate (6) and (octahydrobenzo[e]isobenzofuran-9-yl acetate (9). Each of these was converted into the B-ring mono-epoxide, namely (H-benzo[e]oxireno-2,3-furan-1-yl acetate (7) and a mixture of two racemic diastereoisomers of 9a-bromo-3,3-dimethyl-7,9-dioxoperhydrobenzo[e]oxi- reno[2,3-f]isobenzofuran-1-yl acetate (12), respectively. It was then hoped to deprotonate both (7) and (12) at the 9a position in order to effect migration of the 8,9 double bond to the 9,9a position. Reaction of (7) with a mild base (pyridine) did not effect any reaction. Similar treatment of (12) did remove the 9a proton, but it also effected ring opening of the epoxide, followed by dehydration and dehydrobromination to give an excellent (but unwanted) yield of the aromatized system (±)-7,7-dimethyl-1,3-dioxo-1,3,5,7-tetrahydrobenzo (e]isobenzofuran-9-yl acetate. Dehydrobromination of (9), and deprotonation of the 9a position, similarly formed the aromatic system (e]isobenzofuran-9-yl acetate (11) in good yield.

The Grignard reagent obtained from 2-(6-bromohexyloxy)-tetrahydropyrane, by treatment with anhydrous manganese(II) chloride was transformed to the corresponding organomanganese reagent, which was coupled with E-1-bromo-3-hexeneby treatment with anhydrous manganese chloride. Further deprotection and acetylation furnished E-9-dodecen-1-yl acetate. A second procedure involved the coupling of E-3-hexenylmanganese bromide and 6-bromohexyl acetate. Coupling reactions were carried out at 0 °C, using tetrahydrofurane and N-methylpyrrolidone as co-solvent.

Extension/augmentation of preexisting work carried out in respect of room-temperature single-crystal X-ray structural characterization of trivalent rare earth acetates, crystallized as ‘maximal’ hydrates, Ln(ac)3.x H2O, from aqueous solution under local ambience, suggests the following array to be prevalent: For Ln = La(-)Pr: triclinic P 1 sesquihydrate, i.e. x = 1½, a ≈ 13·4, b ≈ 10·1, c ≈ 8·6 Å, α ≈ 75·6, β ≈ 103·8, γ ≈ 92·8°, Z = 4 mononuclear f.u., conventional R on |F| for Ln = La, Ce, here, being 0·043, 0·058 for No 3199, 4442 independent ‘observed’ (I > 3σ(I)) diffractometer reflections respectively; the complexes have the form of a two-dimensional polymer, in the ac plane, the dominant motif being a chain of lanthanoid atoms of two types linked by acetate bridges along a ... Ln(1)Ln(2)Ln(2)Ln(1)Ln(1)Ln(2) ... with further acetates cross-linking the Ln(1) in the c dimension. For Ln = (Ce(-))Nd: monoclinic P 21/c monohydrate, a ≈ 8·4, b ≈ 8·0, c ≈ 15·0 Å, β ≈ 94°, Z = 4 mononuclear f.u., for the present determinations R were 0·024, 0·044 for No 2019, 2600, the structure being a one-dimensional polymeric form with acetate bridges. For Ln = Sm(-)Lu, (i.e. implicitly with intermediate Ln): triclinic P1 tetrahydrate, a ≈ 10·4, b ≈ 9·2, c ≈ 8·8 Å, α ≈ 118, β ≈ 114, γ ≈ 92°, Z = 2 mononuclear f.u., R were 0·035, 0·030 for No 4583, 4678, the complexes being acetate-bridged dimers. It is of interest that, through the three series, the variation in the degree of hydration is not monotonic. Determinations are also recorded for a pair of crystalline compounds obtained during the attempted crystallization of europium(III) acetate hydrate from aqueous solution acidified with acetic acid (Hac), supporting their formulation as entailing the formation of mixed water/acetic acid solvates Eu(ac)3.2H2O.Hac and Eu(ac)3.H2O.2½Hac, i.e. [Eu2(ac)6(OH2)4].2Hac and [Eu2(ac)6(OH2)2(Hac)2].3Hac with common binuclear cores in which a pair of unidentate water molecule ligands in the former is replaced by a pair of unidentate acetic acid ligands in the latter with relatively minor geometrical change. The former array is rhombohedral R3, a 26·865(7), c 10·328(3) Å (hexagonal setting), Z = 9 binuclear units, isomorphous with the previously reported samarium analogue, and the latter triclinic P1, a 14·131(5), b 8·919(4), c 8·582(3) Å, α 65·41(3), β 84·72(3), γ 84·27(3)°, Z = 1 binuclear unit, R 0·046, 0·051 for No 1700, 2553. An interesting double salt, trisodium hexakis(acetato)ytterbate(III) tetrahydrate, Na3[Yb(ac)6].4H2O, is monoclinic, C2/c, a 13·139(3), b 13·936(2), c 26·030(2) Å , β 91·10(1)°, Z = 8, R 0·053 for No 3467. The eight-coordinate (YbO8) environment is comprised of oxygen atoms from a pair of O,O′-chelating and four unidentate acetate moieties.

A series of new compounds including p-bromo methyl pheno acetate [2]. N-( aminocarbonyl)–p-bromo pheno acetamide [3] , N-( aminothioyl) -p-bromo phenoacetyl amide [4], N-[4-(p-di phenyl)-1,3-oxazol-2-yl]-p-bromopheno acetamide [5],N-[4-p-di phenyl]-1,3-thiazol-2-yl-p-bromo phenoacet amide [6], p-bromopheno acetic acid hydrazide [7] , 1-N-(p-bromo pheno acetyl)-1,2-dihydro-pyridazin-3,6- dione [8], 1-N-(p-bromo pheno acetyl)-1,2-dihydro-phthalazin-3,8- dione[ 9], 1-(p-bromo pheno acetyl)-3-methylpyrazol-5-one [10] and 1-(p-bromo phenol acetyl)- 3,5-dimethyl pyrazole [11] have been synthesized. The prepared compounds were characterized by m.p.,FT-IR and 1H-NMR spectroscopy. Also ,the biological activity was evaluated .

Oxidation of 19β,28-epoxy-18α-oleanan-3-one (1) with chromium(VI) oxide in acetic acid leads to the formation of the 1β,3β;19β,28-diepoxy-3-hydroxy-1,2-seco-18α-oleanano- 2,1α-lactone (2). Its structure follows from spectral data, molecular modelling. Lactone 2 was converted to its acetate 3, methyl 19β,28-epoxy-1,3-dioxo-1,2-seco-18α-oleanan-2-oate (4) and to the stereoisomers at C(3) of methyl 1,3;19β,28-diepoxy-1-oxo-1,2-seco-18α-oleanan-2-oate (6 and 7) and dimethyl 19β,28-epoxy-3-hydroxy-1,2-seco-18α-oleanan-1,2-dioate (8 and 9). Lactone 2 reacts slowly with diazomethane which is indicative for its equilibrium with a small amount of free acid. Alkaline hydrolysis of compound 2 leads to compounds 8 and 9; the reaction involves hydride transfer of a Cannizzaro reaction type. A high rotational barriers were found in compounds 8 and 9. A combination of NMR methods and molecular modelling revealed that most sterically hindered bond in both compounds is the C(1)-C(10) single bond.

Abstract Mannich reaction of 1,3-indandione-1-phenylhydrazone (1) or 1,3-diphenylhydrazone (5) withmorpholine or piperazine gave the Mannich base-phenylhydrazone 2 and 3 or the diphenylhydrazone6 and 7, respectively. Whereas, such reaction with 1 or 5 using primary amines affordedthe indeno[2,1-ƒ]-1,2,4-triazepin-6(2H)-one (4) or its 6-phenylhydrazone (8), respectively.Treatment of 5 with ammonium acetate and formalin afforded 9. The indeno[1,2-ƒ]-1,2,4,5-tetrazepin-10(2H)-one (11) was obtained from the 1,2-diphenylhydrazone 10 and formaldehyde.

The action of a tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), on isolated rat aortic and tail artery strips has been characterized. TPA (10−9 – 10−7 M) produced a graded contraction developing maximum tension over 30–40 min. The contraction was irreversible and was not relaxed by prolonged washing with physiologic saline. Relaxation occurred upon washing with Ca2+-free saline but readdition of Ca2+ restored response. TPA was without significant effect in rat tail arteries in physiologic saline but produced responses in saline containing elevated K+ (15 mM). The protein kinase C inhibitor, CP-46,665-1 (4-aminomethyl-1-[2,3-(di-n-decyloxy)n-propyl]-4-phenylpiperidine dihydrochloride) (5 × 10−5 M), blocked the response to TPA but was without effect on responses to Bay K 8644 (2,6-dimethyl-3-carbomethoxy-5-nitro-4-(2-trifluoromethylphenyl) 1,4-dihydropyridine), KCl, phenylephrine, and B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepin dihydrochloride). The calcium channel antagonist nifedipine and its analogue, 2,6-dimethyl-3,5-dicarbomethoxy-4-(3-cyanophenyl)-1,4-dihydropyridine, inhibited TPA responses with IC50 values of 9.28 × 10−9 and 1.96 × 10−7 M, respectively. Responses to Bay K 8644 in rat aorta were maximum in the presence of elevated KCl (10 mM), but TPA at concentrations of 10−9 and 3 × 10−9 M potentiated responses to Bay K 8644 in physiologic saline to levels approximating those in elevated K+ saline. TPA similarly potentiated responses to Ca2+ in Ca2+-free solution. In the presence of TPA, 10−8 and 3 × 10−8 M, responses to Ca2+ in nondepolarizing saline were potentiated to levels seen under depolarizing conditions. The present results suggest a relationship between protein kinase C and Ca2+ channel activation. However, alternative possibilities, including enhancement of the Ca2+ sensitivity of the contractile apparatus, may also contribute to the observed effects.

(-)-Actinophyllic acid 3, isolated from Alstonia actinophylla, is a promising inhibitor of TAFIa/hippicuricase (0.84 μm). Larry E. Overman of the University of California, Irvine, envisioned (J. Am. Chem. Soc. 2010, 132, 4894) a bold route to 3 based on the aza-Cope/ intramolecular Mannich reorganization of 1 to 3. The absolute configuration of 1 and thus of 3 was set by Noyori hydrogenation of the enone 4. Ozonolysis followed by acetylation delivered the pyridone 6 as an inconsequential mixture of diastereomers. The ketone 9 was assembled by condensation of dimethyl malonate 8 with the acid chloride 7. Cyclization then followed directly on reduction of the nitro group to the amine, to give the crystalline indole 10. Under Lewis acid catalysis, 10 coupled smoothly with the diacetate 6, to give 11 . Selective reduction of the acetate was followed by oxidation, leading to 12. The ketone 12 has only a single acidic stereogenic center. It was not clear whether it could be cyclized without epimerization. A preliminary study with material resolved by enantioselective chromatography, however, showed that this in fact worked well. The LDA kinetically deprotonated the ketone away from the N, at the same time deprotonating the malonate, to give a dianion that underwent smooth oxidative coupling to 13. With 13 in hand, it remained to differentiate the two esters derived from the malonate. This was succinctly accomplished by the addition of vinyl magnesium bromide. Selective reduction of the spontaneously formed lactone 14 cleanly delivered 1. The topological connection between 1 and 3 is not necessarily obvious. Exposure of 1 to HCl gave the amine hydrochloride. Condensation with formaldehyde then gave 15, poised for aza-Cope rearrangement to 2. The enol 2 , then, proceeded via intramolecular Mannich condensation directly to (-)-actinophyllic acid 3.

The zaragozic acids, exemplified by Zaragozic Acid C 3, are picomolar inhibitors of cholesterol biosynthesis. Jeffrey S. Johnson of the University of North Carolina developed (J. Am. Chem. Soc. 2008, 130, 17281) an audacious silyl glyoxylate cascade approach to the oxygenated backbone fragment 1. Intramolecular aldol cyclization converted 1 to 2, setting the stage for the construction of 3. The lactone 2 includes five stereogenic centers, two of which are quaternary. The authors were pleased to observe that exposure of 4 to vinyl magnesium bromide 5 led, via condensation, silyl transfer, condensation, and again silyl transfer, to a species that was trapped with t-butyl glyoxylate 6 to give 7 as a single diastereomer. This one step assembled three of the stereogenic centers of 2, including both of the quaternary centers. The alcohol 7 so prepared was racemic, so the wrong enantiomer was separated by selective oxidation. Intramolecular aldol condensation of the derived α-benzyloxy acetate 1 then completed the construction of 2. Addition of the alkyl lithium 8, again as a single enantiomerically-pure diasteromer, to 2 gave the hemiketal 9. Exposure of 9 to acid initially gave a mixture of products, but this could be induced to converge to the tricyclic ester 10. To convert 10 to 11 , the diastereomer that was needed for the synthesis, two of the stereogenic centers had to be inverted. This was accomplished by exposure to t-BuOK/t-amyl alcohol, followed by re-esterification. The inversion of the secondary hydroxyl group was thought to proceed by retro-aldol/re-aldol condensation. Debenzylation of 11 followed by acetylation delivered 12, an intermediate in the Carreira synthesis of the zaragozic acids. Following that precedent, the ring acetates of 12 were selectively removed, leaving the acetate on the side chain. Boc protection was selective for the endo ring secondary hydroxyl, leaving the exo ring secondary hydroxyl available for condensation with the enantiomerically-pure acid 13. Global deprotection then completed the synthesis of Zaragozic Acid C 3. The key to the success of this synthesis of the complex spiroketal 3 was the assembly of 7 in one step as a single diastereomer from the readily-available building blocks 4, 5, and 6.

(–)-Maoecrystal Z 3 was isolated as a minor constituent from the Chinese medicinal herb Isodon eriocalyx. The synthesis of 3 reported (J. Am. Chem. Soc. 2011, 133, 14964) by Sarah E. Reisman of the California Institute of Technology, featuring as a key step the cyclization of 1 to 2, is a tribute to the power of one-electron reduction for carbon–carbon bond construction. The synthesis began with a Myers alkylation to prepare 6. The amide was reduced to the alcohol with the convenient ammonia–borane complex, and the alcohol was carried on to the iodide 7. The first carbocyclic ring of 3 was prepared by classic chemistry, the condensation of dimethyl malonate 9 with mesityl oxide 8, followed by selective removal of one of the ketone carbonyls. A salt-free Wittig reaction followed by hydrolysis, resolution, and reduction then completed the synthesis of 12. Exposure of 12 to peracid led to the epoxide 13 as an inconsequential mixture of diastereomers. The one-electron Nugent/RajanBabu/Gansäuer protocol was low yielding with methyl acrylate, but dramatically improved when the trifluoroethyl acrylate 14 was used as the acceptor. The lactone 15 was formed as a single diastereomer. Alkylation of 15 with 7 followed by oxidation gave 16, which was deprotected and oxidized to give 1. The cascade cyclization of 1 presumably proceeded by initial one-electron reduction of the more accessible aldehyde. The cyclization of the resulting radical onto the alkene may have been assisted by complexation of the lactone carbonyl with the required second equivalent of SmI2. The Sm enolate so prepared was then added to the second aldehyde to give 2. This cyclization sets one quaternary and three ternary stereogenic centers. Attempted monoprotection of 2 was not successful, so the bis acetate was prepared and ozonized, and the aldehyde was condensed with Eschenmoser’s salt to give 17. Careful monohydrolysis then completed the synthesis of (–)-maoecrystal Z 3

Disorazole C1 3, isolated from fermentation of the myxobacterium Sorangium cellu­losum, shows antifungal and anticancer activity. Amir H. Hoveyda of Boston College applied (J. Am. Chem. Soc. 2014, 136, 16136) recent advances in alkene metathesis from his group to enable the efficient assembly of 2 and so of 3. The ester 1 was assembled from the alcohol 11 and the acid 18. The preparation of 11 began with the enantioselective addition of 5 to 4 to give 6 and then 7, as described by Kalesse (Angew. Chem. Int. Ed. 2010, 49, 1619). Leighton allylation led to 8, that was then coupled with 9 to give 10 with high Z selectivity. Iodination of 10 followed by deprotection then completed the assembly of 11. The starting material for the acid 18 was the allylic alcohol 13. As reported by Cramer (Angew. Chem. Int. Ed. 2008, 47, 6483), exposure of the racemic alcohol 12 to vinyl acetate in the presence of Amano lipase PS converted one enantiomer to the acetate, leaving 13. Methylation of the secondary alcohol followed by acid-mediated removal of the t-butyl ester led to the acid 14, that was converted to the correspond­ing acyl fluoride and coupled with serine Me ester 15 to give 16. After cyclization to the oxazole 17, cross metathesis with five equivalents of 4-bromo-1-butene gave the homoallylic bromide, that was readily eliminated with DBU to give, after saponifica­tion, the acid 18. The cross metathesis of the coupled ester 1, a polyene, with 9 proceeded with remarkable selectivity to give 2, again as the Z geometric isomer. On exposure to the Heck catalyst Pd [(o-tolyl)3P]2, 2 dimerized efficiently. The deprotection was not straightforward, but conditions (H2SiF6, CH3OH, 4°C, 72 h) were found that deliv­ered 3 in 68% yield.

The genus Daphniphyllum consists of 25–30 species of evergreen trees and shrubs of south Asia. The leaves and roots are widely used in Chinese herbal medicine. About 250 alkaloids, many with complex polycyclic structures, have been isolated from these species. Of these, daphenylline 3 is unique in incorporating a benzene ring. Ang Li of the Shanghai Institute of Organic Chemistry envisioned (Nature Chem. 2013, 5, 679) a route to 3 based on the diastereoselective intramolecular Michael cyclization of 1 to 2. Following the work of Piers (J. Org. Chem. 1996, 61, 8439), the preparation of 1 began with the Birch reduction of 4, followed by hydrolysis. Epoxidation followed by elimination and acetylation led to the racemic acetate 5. Hydrolysis with pig liver esterase left one enantiomer of the acetate, that was transesterified with methoxide to give 6 in high ee. Mitsunobu coupling of 6 with the o-nitrobenzenesulfonamide 7 gave 8. After some experimentation, selective α¢-silylation was effected with TBDPSOTf, setting the stage for gold-catalyzed Conia cyclization to 9. Deprotection of the amine fol­lowed by acylation with 10 gave 1, that cyclized smoothly to 2 as a 10:1 ratio of diastereomers. The arene of 3 was constructed by converting 2 into the corresponding vinyl tri­flate. Pd-mediated coupling with 11 gave 12. Under irradiation with strict exclusion of oxygen, 12 cyclized to the dihydro aromatic, that on warming with DBU in the pres­ence of air was oxidized to 13. To close the last ring of 3, the ketone 13 was further oxidized to the enone 14. Desilylation of 14 followed by exposure to Ph3P/I2 gave the iodide 15, that was cyclized under reductive free radical conditions to 16. The hydrogenation of 16 under Pd catalysis delivered the incorrect diastereomer, perhaps because migration to the endocyclic alkene preceded reduction. This problem was solved by using the Crabtree Ir catalyst. Modified Krapcho decarbomethoxylation then gave 17, that was reduced to daphenylline 3.

The sulfate ( + )-didemniserinolipid B 3, isolated from the tunicate Didemnum sp, has an intriguing spiroether core. A key step in the synthesis of 3 reported (Organic Lett. 2007, 9, 5357) by Steven D. Burke of the University of Wisconsin was the selective ring-closing metathesis of 1 to 2. The diol 6 that was used to prepare the ketal 1 was readily prepared from the inexpensive D-mannitol 4. Many other applications can be envisioned for the enantiomerically-pure diol 6 and for the monoacetate and bis acetate that are precursors to it. To set up the metathesis, the β, γ-unsaturated ketone 10 was needed. To this end, the keto phosphonate derived from the addition of the phosphonate anion 8 to the lactone 7 was condensed with phenyl acetaldehyde 9. The derived enone 10 was a 5:1 mixture of β, γ- and α, β-regioisomers. The diol 6 is C2 -symmetrical, but formation of the ketal 1 dissolved the symmetry, with one terminal vinyl group directed toward the styrene double bond, and the other directed away from it. On exposure to the first generation Grubbs catalyst, ring formation proceeded efficiently, to give 2. Williamson coupling with the serine-derived alcohol 11 then gave 12. To establish the secondary alcohol of 13 and so of 3, the more electron rich alkene of 12 was selectively epoxidized, from the more open face. Diaxial opening with hydride then gave 13. With 13 in hand, another challenge of selectivity emerged. The plan had been to attach the ester-bearing sidechain to 13 using alkene metathesis, then hydrogenate. As the side-chain of 3 contained an additional alkene, this had to be present in masked form. To this end, the α-phenylselenyl ester 14 was prepared. Alkene metathesis with 13 proceeded smoothly, this time using the second generation Grubbs catalyst. The unwanted alkene was then removed by reduction with diimide, and the selenide was oxidized to deliver the α, β-unsaturated ester.

The complex polycyclic structure of N-methylwelwitindolinone D isonitrile 3 was assigned in 1999. The welwitinines show an intriguing range of biological activity, including reversal of P-glycoprotein-mediated multidrug resistance in human carcinoma cells. Viresh H. Rawal of the University of Chicago described (J. Am. Chem. Soc. 2011, 133, 5798) the first synthesis of 3, using as a key step the Pd-catalyzed cyclization of 1 to 2. The ketone 1 was assembled by the convergent coupling of 7 with 11. The indole 7 was readily available by Batcho-Leimgruber cyclization of commercial 4 to 5. The expected 3-acylation followed by N -methylation delivered the stable ketone 6. The unstable 7 was prepared as needed. The anisole 8 was the starting material for the preparation of the alicyclic diene 11. Although this synthesis was carried out in the racemic series, enantiomerically enriched 9 could be prepared by Shi epoxidation of the β,γ-unsaturated ketone from Birch reduction The alcohol 7 was not stable to silica gel chromatography. The mixture of 11 with the crude alcohol 7 was therefore activated by the addition of TMSOTf, then added via cannula to aqueous HClO4 in THF to deliver the coupled product 1 as a single diastereomer. The remarkable cyclization of 1 to 2 required extensive screening. Eventually it was found that a combination of ( t -Bu)3 P with Pd(OAc)2 as the Pd source worked well. This concise convergent synthetic strategy makes the welwitinine core 2 available in gram quantities. There were two problems to be solved in the conversion of 2 to 3. The first was the installation of the oxy bridge. Indoles are notoriously sensitive to overoxidation. Nevertheless, addition of an acetone solution of dimethyl dioxirane to the bromo ketone 12 over 24 hours gave clean conversion to 13. The remaining challenge was the conversion of the aldehyde of 13 to the isonitrile. Kim had described the inversion of an oxime to the isothiocyanate. Optimization of this protocol led to the thiourea 14 as the best for this transformation. Mild desulfurization then delivered N -methylwelwitindolinone D isonitrile 3.

The cephalostatins and ritterazines, represented by cephalostatin 1 3, have the remarkable property of inducing apoptosis in apoptosis-resistant malignant cell lines. The total synthesis ( J. Am. Chem. Soc. 2010, 132, 275) of 3 by Matthew D. Shair of Harvard University required the practical preparation of the complex hexacyclic ketones 1 and 2. The preparation of 1 started with irradiation of commercial hecogenin acetate 4 to give the known aldehyde 5 . Reaction of 5 with N -phenyltriazolenedione 6 led to the ketal 7. Oxidative cleavage generated an aldehyde, which on reduction and allylation was converted to 8. Acid-mediated cyclization led to 9. The sidechain of 9 was removed, giving 10, which was selectively reduced, leading to 11. Intramolecular aldol condensation gave 12. The relative configuration of the spiroketal 1 was established by kinetic bromoetherification of the alcohol 13, followed by free radical reduction of the resulting tertiary bromide, and acid-catalyzed equilibration. The synthesis of 2 began with the inexpensive steroid 14. Following the Schönecker protocol, C-H functionalization led to the ketone 15. Pd-mediated coupling of the derived enol triflate with the alkyne gave 16, which was oxidized and cyclized to 17. Simmons-Smith conditions converted the dihydrofuran of 17 into the cyclopropane, which was again opened kinetically with Br (NBS) to set the relative configuration of the spiroketal. Free radical reduction followed by protection and oxidation then completed the preparation of 2. The coupling of 1 and 2 (not illustrated) to form the central pyrazine of 3 followed the precedent of Fuchs, combining the 2-azido ketone derived from 1 with the 2-amino methoxime derived from 2. Remarkably, tens of milligrams of 1 and of 2 were prepared, assuring a reasonable supply of 3 for further studies.

Dithianes such as 1 are readily prepared, from the corresponding ketone or by alkyl­ation. Masayuki Kirihara of the Shizuoka Institute of Science and Technology devel­oped (Tetrahedron Lett. 2013, 54, 5477) an oxidative method for the deprotection of 1 to 2. Konrad Tiefenbacher of the Technische Universität München devised (J. Am. Chem. Soc. 2013, 135, 16213) a hexameric resorcinarene capsule that selectively catalyzed the hydrolysis of the smaller acetal 3 to 4 in the presence of a longer chain acetal. David J. Gorin of Smith College reported (J. Org. Chem. 2013, 78, 11606) the methylation of an acid 5 to 6 using dimethyl carbonate as the donor. Two peroxide-based methods (J. Org. Chem. 2013, 78, 9898; Org. Lett. 2013, 15, 3326) for carboxylic acid methylation (not illustrated) were also recently described. Hisashi Yamamoto of the University of Chicago showed (Angew. Chem. Int. Ed. 2013, 52, 7198) that the “supersilyl” ester 8, prepared from 7, was stable enough to be deprotonated and alkyl­ated, but was easily removed. Michal Szostak and David J. Procter of the University of Manchester uncovered (Angew. Chem. Int. Ed. 2013, 52, 7237) the remarkable cleavage of a C–N bond in an amide 9, leading to the secondary amide 10. This could offer an alternative strategy for difficult-to-hydrolyze amides. Richard B. Silverman of Northwestern University described (J. Org. Chem. 2013, 78, 10931) improved protocols for the formation and removal of the N-protecting 2,5-dimethylpyrrole 11 to give 12. Huanfeng Jiang of the South China University of Technology showed (Chem. Commun. 2013, 49, 6102) that an arenesulfonamide 14 can be prepared by oxidation of the corresponding sodium arenesulfinate 13. Douglas A. Klumpp of Northern Illinois University prepared (Tetrahedron Lett. 2013, 54, 5945) sul­fonamides (not illustrated) by combining a sulfonyl fluoride with a silyl amine. K. Rajender Reddy of the Indian Institute of Chemical Technology developed (Chem. Commun. 2013, 49, 6686) a new route to a urea 17, by oxidative coupling of an amine 15 with a formamide 16.

The macrolactone leucascandrolide A 4, isolated from the calcareous sponge L. caveolata, has both cytotoxic and antifungal activity. The key step in the synthesis of 4 reported (J. Org. Chem. 2007, 72, 5784) by Scott D. Rychnovsky of the University of California, Irvine, was the stereoselective condensation of the aldehyde 1 with the allyl vinyl ether 2 to give 3. The cyclic ether of 1 was assembled from the crotyl addition product 5. Tandem Ru-catalyzed metathesis/hydrogenation converted 5 to the lactone 6. Reduction of 6 to the lactol followed by activation as the acetate gave 7, axial-selective condensation of which with the enol ether 8 delivered the enone 9. Diastereoselective Itsuno-Corey reduction of 9 followed by protecting group exchange and oxidation then gave 1, containing four of the eight stereogenic centers of leucascandrolide A 4. The vinyl ether 2 was readily prepared from the corresponding homoallylic alcohol. Condensation of 1 with 2 involved Lewis acid activation of the aldehyde, addition of the resulting carbocation to the vinyl ether, and cyclization with trapping by bromide ion. In this process, the other four of the eight stereogenic centers were assembled. Three of those centers were formed in the course of the reaction. While stereocontrol was not perfect, the route is pleasingly succinct, so practical quantities of diastereomerically pure 3 could be prepared. To complete the synthesis, the secondary alcohol of 3 was methylated. Selective desilyation of the primary alcohol followed by oxidation and desilylation then set the stage for the Mitsunobu macrolactonization. The intermediates in the Mitsunobu reaction are such that the lactonization can proceed with either inversion of absolute configuration at the secondary center, or retention. While the usually-employed Ph3P gave the lactone with retention of absolute configuration, Bu3P led to clean inversion. The last challenge was the establishment of the (Z) alkene of the side chain. This was accomplished using the Toru protocol. Coupling of the secondary bromide with the Cs salt 12 proceeded with inversion of absolute configuration, to give 13.

Pregnancy as well as congenital deficiency in coagulation inhibitors are recognized as predisposing conditions to thrombosis. Thus, in women with a congenital deficiency, the risk of thrombosis associated to pregnancy is expected to be higher than in normal women (incidence of approximately 1°/..). We have investigated this risk in 16 women with congenital Antithrombin III (AT III) deficiency and in 31 with Protein C (PC) deficiency.In the 16 women with AT III deficiency, 30 pregnancies occured 3 of them were interrupted by provoked abortions and a deep vein thrombosis (DVT) or pulmonary embolism were observed in 2 patients after abortion. Of the 27 other pregnancies, in the absence of any anticoagulant treatment, 17 were complicated by thrombosis (62 %), either during pregnancy (n = 8) or in the post-partun period (n = 9).In the group of 31 women with PC deficiency, 82 pregnancies occured : 16 ended with a provoked abortion, followed by a DVT in one case. Out of the 66 other pregnancies, 17 (25 %) were associated with thrombosis, during pregnancy (n = 5) or in the post-partum (n = 12).Thus, pregnancy is a situation at high risk of thrombosis in PC deficient women, and even higher in AT III deficient ones. No standardized anticoagulant prophylaxis being available, various anticoagulant treatments (mainly SC heparin) were given at various doses, started at different moments of pregnancy to 6 AT III and 3 PC deficient women : 3 and O thrombosis occured respectively.In the post-partum, a thrombosis was observed in 1 of 4 AT III and 2 of 4 PC deficient women who received a treatment. Consequently, an efficient treatment remains to be determined.If a pregnancy is unwanted, estroprogestogens are contra-indicated but progestogen only treatments with chlormadinone acetate, levonorgestrel or low dose of norethisterone were given to 4 AT III and 6 PC deficient women who were simultaneously receiving AVK : no recurrence of thrombosis was observed afer 1 to 3 years of treatment.

Touqui et al (1986) have suggested that phosphorylation by protein kinase C of a 1ipomodulin-1 ike polypeptide extracted from platelets renders it inactive as an inhibitor of phospholipase A2. We have examined this suggestion by measuring thromboxane (Tx) B2 generation and cytosolic free calcium concentration ([Ca++]i) in stimulated, washed human platelets loaded with or without quin-2. Addition of thrombin (0.077, 0.23, 0.77, 2.3 and 7.7 nM) to control platelets produces a dose-related elevation of [Ca++]i (10±5, 50±7, 260±30, 550±25 and 1500±100 nM respectively) and generation of TxB2 (0, 9±4, 45±6, 194±10 and 375±30 pmoles/108 platelets respectively). Preincubation of platelets for 1 min with 1-oleoyl-2-acetyl-rac-glycerol (OAG, 22-198 μM), phorbol myristate acetate (PMA, 1.616 nM) or EGTA (2 mM) produces a marked inhibition of high and low dose thrombin (7.7 nM and 0.77 nM) or NaF (18 mM) induced elevation of [Ca++]i and TxB2 generation. Pretreatment of platelets with the protein kinase C inhibitor, H-7 (60 uM), prevented the inhibition of TxB2 formation induced by PMA (4.816 nM) or OAG (66-198 μM) in either thrombin (0.77 nM) or NaF (18 mM) stimulated platelets. When arachidonic acid (AA, 10 μM) is used as the stimulus, the Δ[Ca++]i is 190±15 nM and TxB2 generation is 35.9±2 pmoles/108 platelets. While pretreatment with 4.8 nM PMA obliterates the AA-induced Δ[Ca++]i and partially reduces (p< 0.05) the TxB2 generation to 27.8+3 pmoles/108 platelets. PMA and OAG pretreatment also inhibits TxB2 generation in thrombin-stimulated, non-quin-2-1oaded platelets. Thus, at least with intact, agonist- and NaF-stimulated platelets, activation of protein kinase C inhibits eicosanoid production.We thank the British Heart Foundation and Ciba-Geigy USA for financial support.

In recent years, a large number of nano-size semiconductors have been investigated for their potential applications in photovoltaic cells, optical sensor devices, and photocatalysts [1, 2, 3]. Nano-size semiconductor particles have many interesting properties due mainly to their size-dependent electronic and optical properties. Appropriately, many speciality of nanomaterials such as CdS and ZnS semiconductor particles, and other metal oxides such as ZnO and lithium-titanate oxide (LTO) have been prepared. However, most of them were prepared with toxic reactants and/or complex multistep reaction processes. Particularly, it is quite difficult to produce LTO nanoparticles, since it typically requires wearisome conditions such as very high temperature over 1000 °C, long producing times, and so on. To overcome such problems, various core/shell type nanocrystals were prepared through different methods such as the hydrothermal synthetic method, microwave, and sonochemistry. Also many coating methods on inorganic oxide nanoparticles were tried for the preparations of various core-shell type nanocrystals. Sonoluminescence (SL) is a light emission phenomenon associated with the catastrophic collapse of a gas bubble oscillating under an ultrasonic field [4]. Light emission of single bubble sonoluminescence (SBSL) is characterized by picosecond flashes of the broad band spectrum extending to the ultraviolet [5, 6]. The bubble wall acceleration has been found to exceed 1011 g at the moment of bubble collapse. Recently observed results of the peak temperature and pressure from the sonoluminescing gas bubble in sulfuric acid solutions [9] were accurately predicted by the hydrodynamic theory for sonoluminescence phenomena [7, 10, 11, 12], which provides a clue for understanding sonochemical reactions inside the bubble and liquid layer adjacent to the bubble wall. Sonochemistry involves an application of sonoluminescence. The intense local heating and high pressure inside the bubbles and liquid adjacent bubble wall from such collapse can give rise to unusual effects in chemical reactions. The estimated temperature and pressure in the liquid zone around the collapsing bubble with equilibrium radius 5 μm, an average radius of bubbles generated in a sonochemical reactor at a driving frequency of 20 kHz with an input power of 179 W, is about 1000 °C and 500 atm, respectively. At the proper condition, a lot of transient bubbles are generated and collapse synchronistically to emit blue light when high power ultrasound is applied to liquid, and it is called multibubble sonoluminescence (MBSL). Figure 1 shows an experimental apparatus for MBSL with a cylindrical quartz cell, into which a 5 mm diameter titanium horn (Misonix XL2020, USA) is inserted [13]. The MBSL facilitates the transient supercritical state [14].in the liquid layer where rapid chemical reactions can take place. In fact, methylene blue (MB), which is one of a number of typical textile dyestuffs, was degraded very fast at the MBSL condition while MB does not degrade under simple ultrasonic irradiation [13]. MBSL has been proven to be a useful technique to make novel materials with unusual properties. In our study, various metal oxides such as ZnO powder [15], used as a primary reinforcing filler for elastomer, homogeneous Li4Ti5O12 nanoparticles [16], used for electrode materials, and core/shell nanoparticles such as CdS coating on TiO2 nanoparticles [17] and ZnS coating on TiO2 nanoparticles [18], which are very likely to be useful for the development of inorganic dye-sensitized solar cells, were synthesized through a one pot reaction under the MBSL condition. Figure 2 shows the XRD pattern of ZnO nanoparticles synthesized from zinc acetate dehydrate (Zn(CH3CO2)2 · 2H2O, 99.999%, Aldrich) in various alcohol solutions with sodium hydroxide (NaOH, 99.99%, Aldrich) at the MBSL condition. The XRD patterns of all powers indicate hexagonal zincite. The XRD pattern for the ZnO nanoparticles synthesized is similar to the ZnO powder produced by a modified sol-gel process and subsequent heat treatment at about 600 °C [19] as shown in Fig.3. The average particle diameter of ZnO powder is about 7 nm. A simple sonochemical method for producing homogeneous LTO nanoparticles, as shown schematically in Fig. 4. First, LiOH and TiO2 nanoparticles were used to prepare LiOH-coated TiO2 nanoparticles as shown in Fig.5. Second, the resulting nanoparticles were thermally treated at 500 °C for 1 hour to prepare LTO nanoparticles. Figure 6 shows a high resolution transmission electron microscope image of LTO nanoparticles having an average grain size of 30–40 nm. All the nanoparticle synthesized are very pure in phase and quite homogeneous in their size and shape. Recently we succeeded in synthesizing a supported nickel catalyst such as Ni/Al2sO3, MgO/Al2O3 and LaAlO3, which turned out to be effective for methane decomposition [20]. Sonochemistry may provide a new way to more rapidly synthesize many specialty nanoparticles with less waste [21]. This clean technology enables the preparation of new materials such as colloids, amorphous particles [22], and various alloys.