Synthesis and structure of 6- and 7-(acylmethyl)pteridines

6-(Acylmethyl)-7-hydroxypteridines 7-14 as well as the isomeric 7-(acylmethyl)-6-hydroxypteridines 15-22 were prepared by condensation of 5,6-diaminouracils 1 and 2 with ethyl aroylpyruvates 3-6 in pyridine and hydrochloric acid, respectively. The structures of the newly synthesized compounds were confirmed by their hydrolysis into the 7-hydroxy-6-methyl- 23 , 24 and 6-hydroxy-7-methylpteridines 25 and 26 . The synthesis of the 2-(methylthio) derivative 28 is also described.     

Reaction of azole condensed quinoxaline N-oxides with acetic anhydride

The reaction of 7-chlorotetrazolo[1,5-α]quinoxaline 5-oxide 6a with acetic anhydride gave 7-chloro-5-(7-chlorotetrazolo[1,5-α]quinoxalin-4-yl)-4,5-dihydro-4-oxotetrazolo[1,5-α]quinoxaline 7a , while the reaction of 7-chloro-1,2,4-triazolo[4,3-α]quinoxaline 5-oxide 6b with acetic anhydride afforded 7-chloro-5-(7-chloro-1,2,4-triazolo[4,3-α]quinoxalin-4-yl)-4,5-dihydro-4-oxo-1,2,4-triazolo[4,3-α]quinoxaline 7b and 7-chloro-4,5-dihydro-4-oxo-1,2,4-triazolo[4,3-α]quinoxaline 8b . The reaction of compound 6a or 6b with acetic anhydride/acetic acid provided 7-chloro-4,5-dihydro-4-oxo-tetrazolo[1,5-α]quinoxaline 8a or compound 8b , respectively.     

Design, synthesis, and cytotoxic activity of Michael acceptors and enol esters in the benzo[b]acronycine series

A series of 2-acyl-6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[b]pyrano[3,2-h]acridin-7-ones (4-6) was prepared by treatment of 6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one (3) with an excess of an appropriate acyl chloride in the presence of aluminum chloride. Treatment of (+/-)-cis-1-hydroxy-2-acyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-ones (9, 10) or (+/-)-cis-1,2-diacyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-ones (2, 11) with hydrochloric acid gave the corresponding 2-acyloxy-6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[b]pyrano[3,2-h]acridin-7-ones, exemplified by acetate 7 and butyrate 8. None of the Michael acceptors 4-6 showed significant antiproliferative activity. Enol esters 7 and 8 were markedly cytotoxic toward L1210 leukemia cells, with IC50 values within the same range of magnitude as (+/-)-cis-1,2-diacetoxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one (S23906-1), currently under phase I clinical trials. In contrast with S23906-1, enol esters 7 and 8 were not reactive toward purified DNA.     

The C-disaccharide alpha-C(1-->3)-mannopyranoside of N-acetylgalactosamine is an inhibitor of glycohydrolases and of human alpha-1,3-fucosyltransferase VI. Its epimer alpha-(1-->3)-mannopyranoside of N-acetyltalosamine is not

The radical C-glycosidation of (-)-(1S,4R,5R, 6R)-6-endo-chloro-3-methylidene-5-exo-(phenylseleno)-7-ox abi cyclo[2. 2.1]heptan-2-one ((-)-4) with 2,3,4, 6-tetra-O-acetyl-alpha-D-mannopyranosyl bromide gave (+)-(1S,3R,4R, 5R,6R)-6-endo-chloro-5-exo-(phenylseleno)-3-endo-(1',3',4', 5'-tetra-O-acetyl-2', 6'-anhydro-7'-deoxy-D-glycero-D-manno-heptitol-7'-C-yl)-7-oxabi cyc lo[ 2.2.1]hept-2-one ((+)-5) that was converted into (+)-(1R,2S,5R, 6R)-5-acetamido-3-chloro-2-hydroxy-6-(1',3',4',5'-tetra-O-acetyl)-2', 6'-anhydro-7'-deoxy-D-glycero-D-manno-heptitol-7'-C-yl)cyclohex -3-en- 1-yl acetate ((+)-10) and into (+)-(1R,2S,5R, 6S)-5-bromo-3-chloro-2-hydroxy-6-(1',3',4',5'-tetra-O-acetyl-2', 6'-anhydro-7'-deoxy-D-glycero-D-manno-heptitol-7'-C-yl)cyclohex -3-en- 1-yl acetate ((+)-19). Ozonolysis of (+)-10 and further transformations provided 2-acetamido-2,3-dideoxy-3-C-(2', 6'-anhydro-7'-deoxy-D-glycero-D-manno-heptitol-7'-C-yl)-D-galac tos e (alpha-C(1-->3)-D-mannopyranoside of N-acetylgalactosamine (alpha-D-Manp-(1-->3)CH(2)-D-GalNAc): 1). Displacement of the bromide (+)-19 with NaN(3) in DMF provided the corresponding azide ((-)-20) following a S(N)2 mechanism. Ozonolysis of (-)-20 and further transformations led to 2-acetamido-2,3-dideoxy-3-C-(2', 6'-anhydro-7'-deoxy-D-glycero-D-manno-heptitol-7'-C-yl)-D-talose (alpha-C(1-->3)-D-mannopyranoside of N-acetyl D-talosamine (alpha-D-Manp-(1-->3)CH(2)-D-TalNAc): 2). The neutral C-disaccharide 1 inhibits several glycosidases (e.g., beta-galactosidase from jack bean with K(i) = 7.5 microM, alpha-L-fucosidase from human placenta with K(i) = 28 microM, beta-glucosidase from Caldocellum saccharolyticum with K(i) = 18 microM) and human alpha-1, 3-fucosyltransferase VI (Fuc-TVI) with K(i) = 120 microM whereas it 2-epimer 2 does not. Double reciprocal analysis showed that the inhibition of Fuc-TVI by 1 displays a mixed pattern with respect to both the donor sugar GDP-fucose and the acceptor LacNAc with K(i) of 123 and 128 microM, respectively.     

Cycloaddition mit ungesättigten Zuckern,VI Die Synthese Diastereomerer 4H-Pyrano [3, 4-d] Isoxazol-4-One

Abstract

By 1, 3-dipolar cycloaddition of benzonitrile oxide to 4, 6-di-O-acetyl-2, 3-dideoxy-D-erythro-hex-2-enono-1, 5-lactone (1), [3aR- (3aα, 6β,7α, 7aα)] - (2) and [3aS-(3aβ, 6β, 7α, 7aα)] -7- (acetyloxy) -6- (acetyloxymethyl) -3a, 6, 7, 7a-tetrahydro-3-phenyl-4H-pyrano [3, 4-d] isoxazole-4-one (3) were prepared in 58 and 7% yield respectively. From 2, [1′ R, 3aR-(3aα, 6β, 6aα)] -6-(1′, 2′-dihydroxymethyl)-6, 6a - dihydro-3-phenyl-furano [3, 4-d] isoxazole-4 (3aH) -one (5) was prepared by deacetylation. The structure of 3 was determined by X-ray analysis.     

Iridium-iron-monocarborane clusters from oxidative insertion reactions of [IrCl(CO)(PPh3)2] with ferracarborane anions

The nine-vertex ferracarborane salt [N(PPh3)2][7,7,7-(CO)3-closo-7,1-FeCB7H8] (1) reacts with an excess of [IrCl(CO)(PPh3)2] in the presence of Tl[PF6] to form, successively, the bimetallic species [7,7,9,9,9-(CO)5-7-PPh3-closo-7,9,1-IrFeCB6H7] (3), in which one {BH}- vertex has formally been subrogated by an {Ir(CO)2(PPh3)} unit, and the trimetallic complex [6,7,9-{Ir(CO)(PPh3)2}-7,9-(mu-H)2-7,9,9-(CO)3-7-PPh3-closo-7,9,1-IrFeCB6H6] (5), which contains an {FeIr2} triangle. The {FeIrCB6} core in 5 resembles that in 3 with, in addition, the Fe...Ir connectivity being spanned by an {Ir(CO)(PPh3)2} fragment and the consequent Fe-Ir and Ir-Ir bonds bridged by hydrido ligands. In contrast to the above, treatment of the 10-vertex diferracarborane salt [N(PPh3)2][6,6,6,10,10,10-(CO)6-closo-6,10, 1-Fe2CB7H8] (2) with the same reagents yields two very different, trimetallic complexes, namely [8,10-{Ir(mu-PPh2)(Ph)(CO)(PPh3)}-8-(mu-H)-6,6,6,10,10-( CO)5-closo-6,10,1-Fe2CB7H7] (6) and [6,7,10-{Fe(CO)3}-6-(mu-H)-6,10,10,10-(CO)4-6-PPh3-closo-6,10,1-IrFeCB7H7] (7). In 6, an exo-polyhedral {IrPh(CO)(PPh3)} moiety is attached to a {closo-6,10,1-Fe2CB7} framework via a PPh2-bridged Fe-Ir bond and a B-HIr agostic-type linkage, the iridium center formally having inserted into one P-Ph bond of a PPh3 unit. Complex 7 contains an {IrFeCB7} cluster core, with an exo-polyhedral {Fe(CO)3} moiety bridging a {BIrFe} triangular face and with an additional Ir-H-Fe bridge. However, this metal atom arrangement reveals that iridium and iron moieties have exchanged exo- and endo-polyhedral sites with respect to the 10-vertex metallacarborane. X-ray diffraction studies upon 3, 5, 6, and 7 confirmed their novel structural features; some preliminary reactivity studies upon these compounds are also reported.     

Synthesis of enantiomerically pure 1,2-diamine derivatives of 7-azabicyclo[2.2.1]heptane. New leads as glycosidase inhibitors and rigid scaffolds for the preparation of peptide analogues

Enantiomerically pure alcohols (-)- and (+)-7-tert-butoxycarbonyl-6-endo-p-toluenesulfonyl-7-azabicyclo[2.2.1]hept-2-en-5-endo-ol ((-)-11 and (+)-11) have been obtained from the Diels-Alder adduct of N-(tert-butoxycarbonyl)pyrroel and 2-bromo-1-p-toluenesulfonylacetylene, including a resolution method. These two alcohols were converted into (+)- and (-)-5-exo-amino-7-(tert-butoxycarbonyl)-2,3-exo-isopropylidenedioxy-7-azabicyclo[2.2.1]heptane ((+)-18 and (-)-18) and (+)- and (-)-5-endo-amino-7-(tert-butoxycarbonyl)-2,3-exo-isopropylidenedioxy-7-azabicyclo[2.2.1]heptane ((+)-19 and (-)-19) after adequate functionalization and desulfonylation steps. The corresponding conformationally constrained bicyclic 1,2-diamines (+)-4, (-)-4, (+/-)-5, (+/-)-6, (+)-7, and (-)-7 were obtained from the protected precursors 18 and 19 and evaluated as glycosidase inhibitors. Diamines (+)-4, (-)-4, (+)-6, and (-)-6 can be seen as new nonpeptide molecular scaffolds for the design of peptide analogues.     

Nitrosylated iron-thiolate-sulfinate complexes with {Fe(NO)}6/7 electronic cores: relevance to the transformation between the active and inactive NO-bound forms of iron-containing nitrile hydratases

The five-coordinated iron-thiolate nitrosyl complexes [(NO)Fe(S,S-C6H3R)2]- (R = H (1), m-CH3 (2)), [(NO)Fe(S,S-C6H2-3,6-Cl2)2]- (3), [(NO)Fe(S,S-C6H3R)2]2- (R = H (10), m-CH3 (11)), and [(NO)Fe(S,S-C6H2-3,6-Cl2)2]2- (12) have been isolated and structurally characterized. Sulfur oxygenation of iron-thiolate nitrosyl complexes 1-3 containing the {Fe(NO)}6 core was triggered by O2 to yield the S-bonded monosulfinate iron species [(NO)Fe(S,SO2-C6H3R)(S,S-C6H3R)]- (R = H (4), m-CH3 (5)) and [(NO)Fe(S,SO2-C6H2-3,6-Cl2)(S,S-C6H2-3,6-Cl2)]2(2-) (6), respectively. In contrast, attack of O2 on the {Fe(NO)}7 complex 10 led to the formation of complex 1 accompanied by the minor products, [Fe(S,S-C6H4)2]2(2-) and [NO3]- (yield 9%). Reduction of complexes 4-6 by [EtS]- in CH3CN-THF yielded [(NO)Fe(S,SO2-C6H3R)(S,S-C6H3R)]2- (R = H (7), m-CH3 (8)) and [(NO)Fe(S,SO2-C6H2-3,6-Cl2)(S,S-C6H2-3,6-Cl2)]2- (9) along with (EtS)2 identified by 1H NMR. Compared to complex 10, complexes 7-9 with the less electron-donating sulfinate ligand coordinated to the {Fe(NO)}7 core were oxidized by O2 to yield complexes 4-6. Obviously, the electronic perturbation of the {Fe(NO)}7 core caused by the coordinated sulfinate in complexes 7-9 may serve to regulate the reactivity of complexes 7-9 toward O2. The iron-sulfinate nitrosyl species with the {Fe(NO)}6/7 core exhibit the photolabilization of sulfur-bound [O] moiety. Complexes 1-4-7-10 (or 2-5-8-11 and 3-6-9-12) are interconvertible under sulfur oxygenation, redox processes, and photolysis, respectively.     

2 + 2] cross coupling of benzene and tropylium ligands in reductively activated piano stool complexes of Mn,Cr, and W

We have established cation/anion coupling reactions between the tropylium ligand in [M(eta7-C7H7)(CO)3]+ (M = Cr, W) and the reductively activated eta4-benzene ligand in [Mn(eta4-C6H6)(CO)3]- (3-) to form [M(CO)3(mu2-eta6:eta5-C7H7-C6H6)Mn(CO)3]; [Cr(CO)3(mu2-eta6:eta5-C7H7-C6H6)Mn(CO)3] can be further reduced to [Cr(CO)3(mu2-eta5:eta4-C7H7-C6H6)Mn(CO)3]2-, in which the tropylium and benzene ligands have undergone a [2 + 2] cross coupling reaction.     

Total synthesis of (-)-(6S,7S,8S,9R,10S,2'S)-membrenone-A and (-)-(6S,7S,8S,9R,10S)- membrenone-B and structural assignment of membrenone-C

[reaction: see text] (-)-(6S,7S,8S,9R,10S,2'S)-Membrenone-A and (-)-(6S,7S,8S,9R,10S)-membrenone-B were prepared in 11 steps (3% and 2.4% overall yield, respectively). Key steps included a tin(II)-mediated aldol followed by a syn selective reduction, giving the C7-C9 stereocenters, a second chain extending aldol coupling, and a p-TsOH-promoted cyclization/dehydration giving the common gamma-dihydropyrone precursor. We have thus established that synthetic (-)-(6S,7S,8S,9R,10S,2'S)-membrenone-A, (-)-(6S,7S,8S,9R,10S)-membrenone-B, and (-)-(6S,7S,8S,9R,10S)-membrenone-C are the enantiomers of the natural products.     

The effects of oligomerization on <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis> Mcm4/6/7 function

Background  

Minichromosome maintenance proteins (Mcm) 2, 3, 4, 5, 6 and 7 are related by sequence and form a variety of complexes that unwind DNA, including Mcm4/6/7. A Mcm4/6/7 trimer forms one half of the Mcm2-7 hexameric ring and can be thought of as the catalytic core of Mcm2-7, the replicative helicase in eukaryotic cells. Oligomeric analysis of Mcm4/6/7 suggests that it forms a hexamer containing two Mcm4/6/7 trimers, however, under certain conditions trimeric Mcm4/6/7 has also been observed. The functional significance of the different Mcm4/6/7 oligomeric states has not been assessed. The results of such an assessment would have implications for studies of both Mcm4/6/7 and Mcm2-7.     

(±)-6-3'a,7-6'-Isowallichilide: A pair of enantiomeric phthalide dimers from Ligusticum chuanxiong with new 6-3'a,7-6' dimerization sites

(+)-6-3'a,7-6'-Isowallichilide and (−)-6-3'a,7-6'-isowallichilide, a pair of enantiomeric phthalide dimers featuring new 6-3'a,7-6' dimerization sites, were isolated from Ligusticum chuanxiong. The structures were elucidated by NMR spectroscopy and X-ray diffraction analysis. Furthermore, the absolute configurations were assigned using experimental and theoretical electronic circular dichroism methods. Their nitric oxide inhibition, antiplatelet aggregation and antioxidant activities were investigated.     

Synthesis of 7a-Aza-benzo[fg]naphthacen-7-one

Phenanthroindolizidine and phenanthroquinolizidine are closely related groups of alkaloids. Since the first isolation of tylophorine 1 in 1935, these natural products have attracted much attention because of their interesting biological activities such as antitumor activity1-3. The obvious problems such as toxicity to nerve system, instability and uneconomical synthetical pathways restrict its application. Kozma reported that C-9, C-14 of tylophorine 1 and C-9, C-15 of cryptopleurine 2 we…     

Synthetic transformations of higher terpenoids: XVIII. Synthesis of optically active 9,10-anthraquinone derivatives

Retro-Diels-Alder decomposition of dodecahydro-endo-4b,12-ethenochrysene-1,4-diones obtained from a tricyclic diterpenoid, levopimaric acid, gave optically active 5-[2-(6-vinyl-2,6-dimethyl-2-carboxycyclohexyl) ethyl]-7-isopropyl-1,4-naphthoquinones which reacted with silyloxybutadienes to produce the corresponding 6- and 7-hydroxyanthraquinones, 5-furyl-7-hydroxytetrahydroanthraquinones, or 5-furyl-7-oxohexahydroanthraquinones. Condensation of the naphthoquinone derivatives with 5-isopropenyl-2,3-dihydrothiophene 1,1-dioxide resulted in the formation of 6,11-dioxodihydro- and 6,11-dioxohexahydroanthra[2,1-b]thiophene 3,3-dioxides. 6- and 7-Hydroxyanthraquinones were also obtained by reaction of dodecahydro-endo-4b,12-ethenochrysene-1,4-diones with Danishevsky diene, followed by cleavage of the polycyclic adducts. The cycloaddition of 5-[2-(-2-carboxy-2,6-dimethyl-6-vinylcyclohexyl)ethyl]-7-isopropyl-1,4-naphthoquinones in the presence of Lewis acids was characterized by increased regioselectivity.     

Reaction of Aminobenzimidazoles with 4-Hydroxy-6-methyl-2-pyrone and 4-Hydroxycoumarine

6- and 7-(4-hydroxy-6-methyl-2-oxo-1-pyridyl)benzimidazoles and 1-(6- and 7-benzimidazolyl)-4-hydroxy-2-oxoquinolines were synthesized by reaction of aminobenzimidazoles with 4-hydroxy-6-methyl-2-pyrone and 4-hydroxycoumarine.     

Novel carboxylated pyrrole- and carbazole-based monomers. Synthesis and electro-oxidation features

Carboxylated pyrrole (Pyr, a index)- and carbazole (Cbz, b index)-containing monomers 6-7a/b and 9a/b have been readily synthesized from the monobenzyl ester of L-glutamic acid and triamine 2 using Clauson-Kaas and amide coupling reactions. In contrast to Pyr-containing compounds 6-7a, and 9a, the three Cbz-containing monomers 6-7b, and 9b have been found electroactive and were successfully electropolymerized on a Pt electrode resulting in the deposition of corresponding insoluble electroconducting polyCOOH polyCbz-films poly(6-7b) and poly(9b).     

New calamenene sesquiterpenes from Tarenna madagascariensis

Four calamenene sequiterpenes, (+)-(7R,10S)-15-hydroxycalamenene (3), (+)-(7R,10S)-2,15-dihydroxycalamenene (4), (+)-(7R,10S)-2-hydroxy-15-calamenal (5), (+)-(7R,10S)-15-calamenal (6), along with the amorphane sesquiterpene (+)-(1S,6R,7R,10S)-1-hydroxy-3-oxo-amorph-4-ene (16), have been isolated from the Madagascan shrub Tarenna madagascariensis (Rubiaceae) and their structures determined by spectroscopic methods and chemical correlations. Furthermore, five known related sesquiterpenes [(+)-(7R,10S)-2-hydroxycalamenene (1), (+)-(7R,10S)-3-hydroxycalamenene (2), (-)-alpha-cadinol (13), cadinenal (14), 6-epicadinenal (15)], and three known lignans [(-)-hinokinin, (-)-dihydrocubebin, (-)-cubebin] were also isolated from the same plant. This is the first report of compounds 3, 4, 5, 6, and 16 from a natural source.     

Total synthesis of optically active lycopladine A by utilizing diastereoselective protection of carbonyl group in a 1,3-cyclohexanedione derivative

We successfully synthesized two enantiomers of bicyclic enones, (7R,7aR)- and (7S,7aS)-9, from the hemiacetal 2a, which we first synthesized from the symmetrical diketone 1a via diastereoselective carbon-oxygen bond formation between one of the carbonyl groups and the chiral alcohol on the C2 side chain in a 2,2-disubstituted 1,3-cycloalkanedione derivative. We also report the total synthesis of natural (+)-lycopladine A [(+)-6] from (7R,7aR)-9 and the formal synthesis of unnatural (-)-lycopladine A [(-)-6] from (7S,7aS)-9.     

Three new 3-benzylbenzofuran-2-one derivatives from Homalium brachybotrys (Flacourtiaceae/Salicaceae s. l.)

Eight phenolic compounds, including two mixtures of two compounds, were isolated from the ethyl acetate extract of leaves and stems of Homalium brachybotrys. They were identified on the basis of spectroscopic data as quercetin-3-O-beta-glucopyranoside, luteolin-7-O-beta-glucopyranoside, 5,6-dihydro-6-beta-glucopyranosyloxy-3-(hydroxyphenyl-methyl)-2(4H)-benzofuranone (cochinolide 6-O-beta-glucopyranoside) (1), 2-(6-benzoyl-beta-glucopyranosyloxy)-5-hydroxybenzyl alcohol (poliothrysoside) (2), 2-(beta-glucopyranosyloxy)-5-hydroxybenzyl alcohol (salirepin) (3), 4,5-dihydro-7a-beta-glucopyranosyloxy-3-(hydroxyphenylmethyl)-2(7aH)-benzofuranone (isocochinolide-7a-O-beta-glucopyranoside) (4), 5,6-dihydro-3-(hydroxyphenylmethyl)-2(4H)-benzofuranone (6-deoxycochinolide) (5) and 3-benzylidine-6-hydroxy-2-benzofuranone (1'deoxy-4,5,6-dehydrocochinolide) (6). Benzofuranones (4), (5) and (6) are new natural products. The compounds isolated support the argument that Homalium is best placed in the Salicaceae s.l.     

Flattening the b(6)h(6)(2-) octahedron Ab initio prediction of a new family of planar all-boron aromatic molecules

The structural chemistry of boron is dominated by 3D structures (polyhedra), while in carbon structural chemistry the planar aromatic structures are more abundant. In this Communication we present results of ab initio calculations showing that the polyhedral boranes can be flattened into planar aromatic structures similar to their carbon analogues. We predicted that a B6H62- octahedron (in Li2B6H6), a B5H52- trigonal bipyramid (in Li2B5H5), a B7H72- pentagonal bipyramid (in Li2B7H7), and a B10H84- bioctahedron with a joint edge (in Li4B10H8) can be reduced to a planar aromatic B6H66- hexagon (in Li6B6H6), to a planar pentagon B5H56- (in Li6B5H5), to a planar heptagon B7H76- (in Li6B7H7), and to a naphthalene-like B10H810- (in Li10B10H8). Ab initio prediction of these new planar aromatic boranes shows that a large new family of planar aromatic all-boron molecules is possible.