Tetracyclines Communication 22. Stereochemistry of 2- and 3-substituted 10-oxo-9-hydroxy-9-methyl-1,2,3,4,4a,9,9a,10-octahydroanthracenes

Summary Intramolecular cyclization reactions were investigated, and the configurations were proved of 2- and 3-substituted 10-oxo-9-hydroxy-9-methyl-1,2,3,4a,9,9a.10-octahydroanthracenes of type (I), which are possible intermediaries for the synthesis of tetracyclines and their analogs.Translated from Izvestiya Akademii Nauk SSSR, Setiya Khimicheskaya, No. 6, pp. 1024–1035, June, 1964     

Pathways for ring inversion in 9, 10-dihydroanthracene, 9, 10-dihydrophenanthrene,and 7, 12-dihydropleiadene: Combined molecular orbital and molecular mechanics study

The combined semiempirical AM1 and MM2 study of the ring inversion processes in 9, 10-dihydroanthracene ( 1 ), 9, 10-dihydrophenanthrene ( 2 ), and 7, 12-dihydropleiadene ( 3 ) predicts planar transition states for 1 and 2 , in accord with earlier assumptions. In the case of 3 , however, a nonplanar, chair-like transition state is located on the potential energy surface in contrast with previous conclusions. Implications of the nonplanar TS on the rationalization of available experimental data are discussed. The calculated barriers for ring inversion in 1–3 are in reasonable agreement with both experiment and previous theoretical results. In general, AM1 is found to slightly underestimate the barriers as compared to the MM2 calculations.     

反式-9, 10-二氢-9, 10-二(1-萘基)-9, 10-菲二醇的包合现象 与晶体结构

按文献方法合成了一个螯形主体分子,反式-9,10-二氢-9,10-二(1-萘基)-9,10-菲二醇。研究发现该主体可以和一些含氮杂环化合物形成一定比例的晶体包合物。用X-射线衍射分析二环己胺包合物的晶体结构表明,包合物中主客体之间存在O-H…N氢键相互作用,客体分子包合在主体分子形成的空腔中。     

10,10-二苄基-9(10H)蒽醇的酸催化选择性环化反应

蒽酮(1)与3,5-二甲氧基苯甲醛(2)在吡啶/哌啶中反应生成10-(3,5-二甲氧基苯甲亚基蒽酮(3); 3经Pd/C催化氢化生成10-(3,5-二甲氧基苄基蒽酮(4); 4与3-甲氧基苄基氯(5)进行相转移催化烷基化反应生成10-(3,5-二甲氧基苄基)-10-(3-甲氧基苄基)蒽酮(6); 6经NaBH₄还原生成10-(3,5-二甲氧基苄基)-10-(3-甲氧基苄基)-9(10H)-蒽醇(7); 7在酸催化下发生选择性1,7-脱水反应, 生成高三蝶烯(homotriptycene) (8). 其反应机理可能是7在酸存在下生成正碳离子中间体, 然后选择性地亲电进攻富电荷的3,5-二甲氧基苯基, 而不进攻3-甲氧基苯基.     

The Synthesis of Some 9-,10-, and 11-Membered Ring Compounds Containing a Nitrogen Atom: 2,3,4,5,6,7-Hexahydro-1H-3-Benzazonines, 1,2,3,4,5,6,7,8-Octahydro-3-Benzazocines,and 2,3,4,5,6,7,8,9-Octahydro-1H-3-Benzazacy-cloundecanes

In previous papers the syntheses of seven-¹ and eight-membered ^{2a, 2b} ring compounds of the general formulas 5a, b have been described and the nine-membered^2c homolog^5c briefly mentioned. It was of interest to see whether the method of ring formation using an amino acid of type 3 was applicable to the preparation of larger ring systems. In this paper we would like to report the preparation of the bicyclic amines 5 which are the 9-, 10-, and 11-membered ring homologs of this series.     

The x-ray structure analysis of 17-beta-bromoacetoxy-9-beta, 10-alpha-androst-4-en-3-on

The structure of 17β-bromacetoxy-9β, 10α-androst-4-en-3-one has been determined by three-dimensional X-ray crystallographic methods. The crystals of the restrosteroid belong to the orthorhombic space group P2₁2₁2₁ with four molecules per unit cell. The cell constants are a = 11.32 Å, b = 13.71 Å and c = 12.52 Å. The absolute configuration of the molecule has been determined by the anomalous dispersion method. Bond length, bond angles and distances of atoms from ‘best planes’ are given. Ring A represents a distorted half-chair, ring B and C a chair and ring D an envelope conformation. The molecule shows, contrary to normal 9α, 10β-steroids, a bent shape.     

Evidence for homo-conjugation between two revolving 14pi-electron systems in 10b-methyl-10c-[2-(10b,10c-dimethyl-10b,10c-dihydropyrenyl)]-10b,10c-dihydropyrene

Ring contraction followed by an elimination reaction on anti-9-methyl-18-trans-2-(10b,10c-dimethyl-10b,10c-dihydropyrenyl)-2,11-dithia[3,3]metacyclophane gave the desired compound 10b-methyl-10c-[2-(10b,10c-dimethyl-10b,10c-dihydropyrenyl)]-10b,10c-dihydropyrene. 1H NMR spectroscopic analysis indicated a ring current effect over a considerable distance from the macro-molecular plane of each of the aromatic rings with the two pi systems freely rotating. Bathochromic shifts and peak broadening in its electronic spectrum clearly supports the presence of through-space pi-pi interactions between the two aromatic rings. This should serve as a good model to verify homo-conjugation effect in such a novel system where the two pi systems are freely revolving.     

Spontaneous cyclization of (acridin-9-ylmethyl)thioureas to spiro [dihydroacridine-9′(10′H),5-imidazolidine]-2-thiones,a novel type of acridine spirocycles

Novel acridine spirocompounds, spiro[dihydroacridine-9′(10′H),5-imidazolidine]-2-thiones have been prepared by the spontaneous cyclization of 1-substituted 3-(acridin-9-ylmethyl)thioureas, which were obtained from 1-(acridin-9-yl)methanamine, N-(acridin-9-ylmethyl)propan-1-amine, and N-(acridin-9-ylmethyl)benzylamine and alkyl/aryl isothiocyanates, as continuation of our previous studies on new acridine spirocycles. Imidazolidine-2-thiones thus obtained were subsequently transformed with mesitylnitrile oxide to imidazolidine-2-one analogues, some of which partly reopened to the corresponding (acridin-9-ylmethyl)ureas. An unusual spirocyclization via a CH carbanion instead of the N-1 nitrogen has been found for 3-(acridin-9-ylmethyl)-1-(acridin-9-yl)thioureas possessing two acridine rings. Structural modifications in positions 1, 3, and 4 of the spiro ring together with ¹H, ¹³C, and ¹⁵N NMR spectroscopy and X-ray crystallography have been employed to rationalize a general propensity of various 9-substituted acridines to undergo easy spirocyclization.     

Photo-induced Coupling Reaction of 1, 1-Diphenyl-2, 2-dicyanoethylene with 10-Methyl-9, 10-dihydroacridine

In a previous communication1, we reported a novel photo-induced coupling of 9-fluorenylidenemalononitrile 1 with the coenzyme NADH model 10-methyl-9, 10-dihydroacridine (AcrH2) to give 9-dicyanomethyl-9-(10-methyl-9-acridinyl)fluorene and proposed a mechanism involving photo-induced electron transfer-proton transfer and radical coupling. This is a scarce mechanism for the reaction of NADH models2, which usually takes place by a formal hydride transfer pathway3. In view of the novelty of t…     

反式9, 10-二氢-9, 10-二苯基-9, 10-菲二醇包结性能的研究

合成了一种具有螯形结构的反式-9, 10-二氢-9, 10-二苯基-9,10-菲二醇(1)作为主体分子。它能与许多有机小分子化合物, 诸如DMF, DMSO, 吡啶, 哌啶, 喹啉, 异喹啉等形成包结化合物。本文还报道了这些包结化合物的IR, 粉末XRD的表征, 用^1H NMR谱测定了它们的分子摩尔比。DMF包结物的单晶四圆X衍射结果表明主体分子1与客体分子形成的包结物为配位笼状包合物。     

Study on second harmonic generation of 9-benzylidene-substituted-10-methyl-9,10-dihydroacridines

Eight 9-benzylidene-substituted-10-methyl-9,10-dihydroacridine derivatives were synthesized from acridine as starting material and were characterized by 1H-NMR, 13C-NMR, Ms and elemental analysis. The second harmonic generation (SHG) values of these compounds were determined in powder using Nd:YAG as a laser source, as compared with urea powder, and the values of second-order polarizabilities (betaxxx), the values of the composite magnitude (betaCTmicrog) of molecular hypersusceptibilities and their moment of these compounds were obtained by the solvatochromic method under ground state for everyone. The results showed that SHG value of 10 is higher than that of urea; the betaCTmicrog of 5 (107.8 x 10(-30) esu) is lower than that of 4-nitro-N,N-dimethylaniline (30 x 10(-30) esu); the betaCTmicrog of 7 (350.8 x 10(-30) esu) and 10 (244.6 x 10(-30) esu) are higher than that of 4-nitro-N,N-dimethylaniline; the betaCTmicrog of 8 (3553 x 10(-30) esu), 11 (1187 x 10(-30) esu) and 12 (1163 x 10(-30) esu) are much more higher than that of 4-nitro-N,N-dimethylaniline. The results demonstrated that this series of compounds possesses good second-order nonlinear optical (NLO) property. The regular relationship could not be obtained between electronegativity of substituents (R) attached to benzylidene ring and SHG values or betaCTmicrog values although the Rs are different in electronegativity and should make an effect on the extent of intramolecular electron-transfer and would consequently influence SHG or betaCTmicrog. The electron-withdrawing ability of R from benzylidene ring played an important role on lambdamax of these compounds.     

Extreme projection of a proton into the pi-cloud of an aromatic ring: record shielding of an aromatic proton in trans-10b-methyl-10c-(1-naphthyl)-10b,10c-dihydropyrene

A synthetic sequence involving dithiametacyclophane --> metacyclophanediene --> dihydropyrene was employed to prepare trans-10b-methyl-10c-(2-naphthyl)- and trans-10b-methyl-10c-(1-naphthyl)-10b,10c-dihydropyrene 5 and 6, respectively. Both exhibit a strong diamagnetic ring current despite the introduction of an internal bulky substituent within the pi-electron cloud. Their electronic spectra suggest interaction between the two near-perpendicular naphthyl and dihydropyrenyl pi systems, resulting in red shift and band broadening. All naphthyl protons are well resolved in their 1H NMR spectra due to a strong shielding effect of the dihydropyrene ring. The most shielded protons in 5 and 6 are H1' and H2' at delta 2.47 and 1.42, respectively, being 5.25 and 5.95 ppm shifted from those of reference protons. There is evidence for free rotation on the NMR time scale of the 2-naphthyl ring in 5 with a preference for a particular conformer, whereas the 1-naphthyl ring in 6 is conformationally rigid with its H2' projecting deeply into the pi-cloud, thus accounting for the most shielded aromatic proton (H2' in 6) reported to date.     

Photochemical reaction of 9-nitro-substituted anthracene-like molecules 9-methyl-10-nitroanthracene and 12-methyl-7-nitrobenz[a]anthracene

Photolysis of 9-methyl-10-nitroanthracene in chloroform or methanol produces mainly two products 9-methyl-9-nitrosoanthracen-10-one and 9,10-anthraquinone in about 4:1 ratio under ambient air. The formation of 9-methyl-9-nitrosoanthracen-10-one confirms the proposed excited state rearrangement reaction of the nitro group peri to two hydrogens and perpendicular to the aromatic rings. The nitro group rearranges to a nitrite, followed by breaking of the N–O bond producing NO radical. The NO radical further forms a bond with the carbon on the opposite site of the benzene ring through radical recombination. Photolysis of 12-methyl-7-nitrobenz[a]anthracene produced several nitroso ketone-like compounds which further convert to an aldehyde. Photolysis of the desmethyl nitro compounds, 9-nitroanthracene and 7-nitrobenz[a]anthracene, produced the respective quinones.     

One-electron reduction of 9, 10-anthraquinone, 1-amino-9, 10-anthraquinone and 1-hydroxy-9, 10-anthraquinone in aqueous-isopropanol-acetone mixed solvent: A pulse radiolysis study

The semiquinone radicals produced by one-electron reduction of 9, 10-anthraquinone, 1-amino-9, 10-anthraquinone and 1-hydroxy-9, 10-anthraquinone have been characterized in aqueous-organic mixed solvent comprising of 30.2 mol dm⁻³ water, 5 mol dm⁻³ isopropanol and 1 mol dm⁻³ acetone, using the pulse radiolysis technique. Spectroscopic characteristics, the kinetic parameters of formation and decay and one acid dissociation constants of the semiquinones and one-electron reduction potentials of the quinones have been estimated. The characteristics of the present semiquinone systems have been compared with those of other similar systems. The observed differences in characteristics of the semiquinones due to different substitutions have been analysed.     

Asymmetric allyl- and crotylboration with the robust, versatile, and recyclable 10-TMS-9-borabicyclo[3.3.2]decanes

The remarkable versatility and selectivity of the 10-(trimethylsilyl)-9-borabicyclo[3.3.2]decanes (10-TMS-9-BBDs) in the allyl- and crotylboration of representative aldehydes are reported. The new reagents are prepared through air-stable crystalline pseudoephedrine borinic ester complexes of the 10-TMS-9-BBDs (4), which are available in 63% overall yield from B-MeO-9-BBN through a simple two-step procedure. These complexes 4 are directly converted to the corresponding B-allyl-10-TMS-9-BBDs (1) with allylmagnesium bromide, which either can be isolated (98%) or used in situ for the allylations. The remarkable enantioselectivity (96 to > or =99% ee) of these reagents in the rapid (<3 h), asymmetric allylboration process at -78 degrees C is only slightly diminished when it is conducted at 25 degrees C, a phenomenon attributable to its rigid bicyclic structure. In addition to providing the homoallylic alcohols 6 efficiently (68-80%), the procedure also permits the efficient recovery of 4 (68-84%) for the direct regeneration of 1. Alternatively, an oxidative workup procedure can be used for the preparation of 6. The reagent gives predictable stereochemistry and exhibits an extremely high level of reagent control in the allylboration of d-glyceraldehyde acetonide. A simple and efficient procedure has been developed for the preparation of all four geometric and enantiomeric isomers of the B-crotyl-10-TMS-9-BBDs (10) from optically pure enantiomers of B-MeO-10-TMS-9-BBD (3). These reagents 10 also add rapidly (<3 h) and efficiently to representative aldehydes at -78 degrees C, providing ready access to all four of the possible stereoisomers of the beta-methyl homoallylic alcohols 12-15 (69-92%) in high dr (> or =98:2) and ee (94-99%).     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 9. Phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline,benzo[f]phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline,and benzo[h]-phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline

The synthesis of three novel polycyclic heterocyclic ring systems are reported via photocyclization. The specific final products in these ring systems are: phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline ( 13 ), benzo[h]-phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline ( 14 ), and benzo[f]phenanthro[9′,10′:4,5]thieno[2,3-c]quinoline ( 15 ).     

Determination of Arene Oxides by a Gas Chromatography-Mass Spectrometry System: Thermal Reactions of 9, 10-Epoxy-9, 10-Dihydrophenanthrene

Abstract

An analytical technique involving the use of a gas chromatograph coupled to a mass spectrometer-computer system, has been developed to detect arene oxides using 9, 10-epoxy-9, 10-dihydro-phenanthrene as a model substrate. The gas chromatograph was equipped with a hydrogen flame ionization detector and a high-resolution glass capillary column coated with SE-52 (methyl phenyl silicone). Two simultaneous thermal reactions (deoxygenation and rearrangement) of 9, 10-epoxy-9, 10-dihydrophenanthrene in the gas chromatograph were observed. The method developed was compared with a conventional method utilizing a packed glass column. Under the latter conditions neither thermal reactions nor 9, 10-epoxy-9, 10-dihydrophenanthrene were detected. The identification of the reactant and products was achieved by comparison of retention times and mass spectral fragmentation patterns obtained from authentic samples.     

Syntheses of 9-Triptycylisothiocyanate, (10-Amino-9-triptycyl)carboxylic Acid,and Their Derivatives

In the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 9-triptycylisothiocyanate has been synthesized in 91% yield from carbon disulfide and sterically hindered 9-triptycylamine at room temperature. 9-Triptycylisothiocyanate can be further converted to 1-benzyl-3-(9-triptycyl)thiourea. (10-Amino-9-triptycyl)carboxylic acid has also been successfully synthesized via a three-step route starting from methyl 10-nitroanthracene-9-carboylate. Its amino and carboxylic groups can undergo acetylation and amidation, respectively.     

The synthesis of 3,4,4a,9a-tetrahydro-2(1H)-carbazolones

Cyclization of 4-(1-methylindol-3-yl)-2-butanone and the corresponding 1-benzyl analog in trifluoroacetic acid furnishes 9-methyl- and 9-benzyl-3,4,4a,9a-tetrahydro-2(1H)-carbazolone, respectively. Under the same conditions, 4-(indol-3-yl)-2-butanone gives the dimer, 3-(3-oxo-butyl)-2-[3-(3-oxobutyl)-2-indolinyl] indole. When boron trifluoride etherate is used instead of trifluoroacetic acid, the desired 3,4,4a,9a-tetrahydro-2(1H)-carbazolone is obtained. The determination of the structure of the tetrahydrocarbazolones is described and the stereochemistry of the ring fusion is discussed.     

Synthesis of representative 10-aryl-, 10-aralkyl- and 10-heteraryl-9H-naphtho[1′,2′:4,5]thiazolo[3,2-b]- [1,2,4]triazin-9-ones as potential anti-HIV agents

To prepare the title compounds, cyclocondensation of 1-amino-2-iminonaphtho[1,2-d]thiazole ( 2 ) with some representative glyoxylic acid derivatives was investigated. Heating 2 with methyl phenylglyoxylate ( 3a ) in methanol afforded only the open chain intermediates 4a,b . However, when this reaction was performed in re-fluxing glacial acetic acid, the expected compound, 10-phenyl-9H-naphtho[1′,2′:4,5]thiazolo[3,2-b][1,2,4]- triazin-9-one ( 5a ) was produced in 27% yield. Similar treatment of 2 with benzyl-, 2-furyl- and 2-thienylgly-oxylic acids 3b-d gave the corresponding 10-benzyl-, 10-(2-furyl)- and 10-(2-thienyl)-9H-naphtho[1′,2′:4,5]thi-azolo[3,2-b][1,2,4]triazin-9-ones 5b-d in 48–67% yields. As by-products, 9-benzoyl- and 9-(2-thenoyl)naphtho-[1′,2′:4,5]thiazolo[3,2-b][1,2,4]triazoles 6a,d were also isolated. Compound 5a was selected for in vitro anti-HIV evaluation but found to be inactive.