Novel erythromycin A derivatives: synthesis of 11,12-benzoxazine ketolides

A novel series of 11,12-benzoxazine ketolide derivatives of erythromycin A has been synthesized. The C11,C12-benzoxazine structure was constructed stereoselectively through an intramolecular Michael addition of a C12-O-(2-aminophenyl) group to the enone functionality of the 10,11-anhydro erythromycin A derivative 3.     

Synthesis of novel 6,11-O-bridged bicyclic ketolides via a palladium-catalyzed bis-allylation

A bridging chemistry process was developed to form an ether bridge between 6-O and 11-O of erythromycin A via a tandem or stepwise palladium-catalyzed bis-pi-allylation. By applying this bridging process, new 6,11-O-bridged bicyclic ketolides (BBKs) were synthesized. These BBKs showed good antibacterial activities against the macrolide-susceptible strains as well as mef-resistant strains and served as a good core for further modifications to study the structure-activity relationship (SAR) and to overcome bacterial resistance. [reaction: see text]     

Synthesis of 6-chloro and 6-fluoro-4-hydroxyl-2-quinolone and their azo disperse dyes

<正>In this study,6-chloro-4-hydroxy-2-quinolone and 6-flouro-4-hydroxy-2-quinolone were synthesized from corresponding dianilides.These compounds were coupled with some diazotized aromatic amines to give the corresponding azo disperse dyes.The structures of the quinolone derivatives and new azo dyes were confirmed by UV-vis,FT-IR,~1H NMR and elemental analysis.     

A novel synthesis of α-fluoroacetonitriles. Application to a convenient preparation of 2-fluoro-2-phenethylamines

α-Fluorophenylacetonitriles (3) are readily prepared by the treatment of the corresponding benzaldehyde cyanohydrin trimethylsilylethers (2) with diethylaminosulfur trifluoride (DAST). This method for the introduction of fluorine alpha to a cyano group is also applicable to the cyanohydrin trimethylsilylethers of aromatic ketones. Diborane reduction of the α-fluorophenylacetonitriles (3) yields 2-fluoro-2-phenethylamines (4).     

Synthesis of fluorodinitromethane and 2-fluoro-2, 2-dinitroethanol

Conclusions The authors have obtained fluorodinitromethane and 2-fluoro-2, 2-dinitroethanol and studied some of their physiocochemical properties.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 912–914, April, 1968.     

Synthesis of 2-fluoro- and 6-fluoro-(2S,3R)-(3,4-dihydroxyphenyl)serine as potential in vivo precursors of fluorinated norepinephrines.

The title compounds were prepared by the aldol condensation of 3,4-dibenzyloxy-2-fluorobenzaldehyde and 4,5-dibenzyloxy-2-fluorobenzaldehyde with the oxazolidinone 2, a chiral glycine equivalent. Removal of the chiral auxiliary and blocking groups produced the target amino acids 2-fluoro- and 6-fluoro-(2S,3R)-(3,4-dihydroxyphenyl)serine (1b and 1c) in >98% ee.     

Synthesis of macrolide antibiotics. 20. Synthesis of erythronolide A

A complete, stereocontrolled synthesis for erythronolide A was carried out by fusion of the (C⁹-C¹³)+(C⁷-C⁸)+(C¹-C⁶) fragments from levoglucosan in 61 steps with 0.28% total yield.For previous communication, see [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 195–199, January, 1990.     

Fluorinated chromenes. III. Synthesis of 3-fluoro-2,2-dimethyl-2H-chromenes

The reaction of 2-fluoro-1,1-dimethoxy-3-methylbut-2-ene ( 3 ) with phenols in dry pyridine leads to 3-fluoro-2,2-dimethyl-2H-chromenes. 3-Fluoro analogues of the natural insect antijuvenile hormones Precocene I ( 1a ) and II ( 1b ) have been prepared by this method.     

Synthesis and structure of o-bis(2-fluoro-2,2-dinitroethyl)-nitromethyl ester of 2′-fluoro-2′, 2′-dinitroethyl-2″-fluoro-2″-nitroethylenecarboxime

Conclusions The product of conversion of O-bis(2-fluoro-2,2-dinitroethyl)nitromethylbis(2-fluoro-2,2-dinitroethyl)carboxime in methanol or ether is O-bis(2-fluoro-2,2-dinitroethyl)nitromethyl-2-fluoro-2,2-dinitroethyl-2'-fluoro-2-nitroethylenecarboxinie, the structure of which has been established by x-ray diffraction analysis.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2019–2021, September, 1987.     

Molecular structure of 1-phenyl-1-fluoro-5-methylquasisilatrane (2-phenyl-2-fluoro-1,3-dioxa-6-aza-6-methyl-2-silacyclooctane)

The crystal and molecular structure of 1-phenyl-1-fluoro-5-methylquasisilatrane PhFSi(OCH₂CH₂)₂NMe was investigated by X-ray diffraction at 100 K. The coordination polyhedron of the silicon atom in the molecule is a slightly distorted trigonal bipyramid containing fluorine and nitrogen atoms in the axial positions and two endocyclic oxygen atoms and the carbon atom of the phenyl group at three vertices of the equatorial plane.     

2-氨基-6-氟-9-(4-羟基-3-羟甲基丁基)嘌呤的合成

报道了2-氨基-6-氟-9-(4-羟基-3-羟甲基丁基)嘌呤(1)的合成, 通过对起始原料2-氨基-6-氯-9-(4-乙酰氧基-3-乙酰氧甲基丁基)嘌呤(2)水解脱去乙酰基, 得到2-氨基-6-氯-9-(4-羟基-3-羟甲基丁基)嘌呤(3). 化合物3与三甲胺乙醇溶液在混合溶剂[V(THF)∶V(DMF)＝3∶1]中反应得到相应的氯化铵盐4, 然后与KF在DMF溶剂中反应, 得到化合物1. 产品经UV-vis, IR, ¹H NMR, ¹⁹F NMR和MS表征. 考察了反应温度、氟化试剂等因素对氟化反应的影响, 为6位含氟的嘌呤核苷类化合物的合成提供了一种直接、简易的新方法.     

Synthesis and conformation of 2-fluoro-3-ketoestrane derivatives

Treatment of 3-methoxy-17β-acetoxyestra-2,5(10)-diene with perchloryl fluoride in aqueous dioxane or tetrahydrofuran yielded a 2-fluoro-3-ketosteroid with unusual properties. Unlike the known 2-fluoro-19-nortestosterone, this fluoroketone possessing a 5(10) double bond easily lost hydrogen fluoride to form estradiol 17-acetate; aromatization took place on melting, on exposure to pyridine or acid or even during chromatography on silica gel or Florisil. Because of the Δ-5(10) structure and the absence of the C₁₉ Me group, it is difficult to infer the exact orientation of the 2-fluorine substituent from its effect on the NMR spectrum, CD or the CO absorption in the IR. However, the properties of certain derivatives suggested that the fluorine substituent was 2β. Treatment of the unsaturated fluorketone with peracid gave a mixture of epoxides which on basic hydrolysis furnished two 2-fluoro-10-hydroxy-17-acetoxyestr-4-en-3-ones epimeric at C₁₀. The UV and NMR spectra of the 10-hydroxy epimer indicated an equatorial 2β-orientation of fluorine, whereas the 10β-hydroxy epimer showed an axial 2β-fluorine substituent which could be isomerized by acid to the more stable equatorial 2-configuration.     

Synthesis of 3-substituted 2-fluoro- and 2,2-difluoroaziridines

A new route for the synthesis of stable 3-alkyl- and 3-aryl-2(,2)-(di)fluoroaziridines was developed by hydride reduction of novel alpha-bromo- and alpha-chloro-alpha(,alpha)-(di)fluoroketimines and subsequent ring closure of beta-fluorinated beta-chloro- and beta-bromoamines. This is the first report on the synthesis of 2,2-difluoroaziridines sensu stricto.     

Synthesis of bis-(2-fluoro-2, 2-dinitroethyl) nitramine and tris-(2-fluoro-2,2-dinitroethyl) amine

Russian Chemical Bulletin -     

Process development and manufacture of potassium 2-fluoro-6-hydroxyphenyltrifluoroborate

The development of a phase-appropriate manufacturing-scale synthesis of potassium 2-fluoro-6-hydroxyphenyltrifluoroborate was achieved. Investigations into improving the yield and robustness indicated that pH of the reaction medium is a critical process parameter. Additional development resulted in replacing tartaric acid with citric acid, resulting in improved process robustness and enabling scale-up to >10 kg.     

Synthesis and reactions of 7-fluoro-4-methyl-6-nitro-2-oxo-2H-1-benzopyran-3-carboxylic acid: a novel scaffold for combinatorial synthesis of coumarins

7-Fluoro-4-methyl-6-nitro-2-oxo-2H-1-benzopyran-3-carboxylic acid has been prepared as a novel scaffold for combinatorial synthesis of coumarins. The scaffold has three points of diversity. The optimal conditions for its reactions with different nucleophiles in solid phase were obtained. Sixteen coumarin derivatives with different structures were designed and synthesized in solid phase to demonstrate its application as a scaffold for combinatorial synthesis of coumarins. Thirteen of these derivatives were obtained in high yields. Many of these model compounds fluoresce. Combinatorial libraries constructed with this novel scaffold may have interesting biological or physical properties.     

Synthesis of novel 6-enaminopurines

Two different approaches have been used for the synthesis of 6-enaminopurines 6 from 5-amino-4-cyanoformimidoyl imidazoles. In the first approach imidazoles 1 were reacted with ethoxymethylenemalononitrile or ethoxymethylenecyanoacetate under mild experimental conditions and this led to 9-substituted-6-(1-amino-2,2-dicyanovinyl) purines 6a-f or 9-substituted-6-(1-amino-2-cyano-2-methoxycarbonylvinyl) purines 6g-k. These reactions are postulated to occur through an imidazo-pyrrolidine intermediate 7, which rapidly rearranges to the 6-enaminopurine 6. In the second approach 6-methoxyformimidoyl purines 3, prepared in two efficient steps from 5-amino-4-cyanoformimidoyl imidazoles 1, were reacted with malononitrile and methylcyanoacetate with a mild acid catalysis (ammonium acetate or piperidinium acetate) to give 6-enaminopurines 6a, 6d, 6f, 6g and 6k in very good yields. Only low yields were obtained for the 6-enaminopurine 6j, as competing nucleophilic attack on C-8 of either 3d or 6jcauses ring opening with formation of pyrimido-pyrimidines 11 and 10a respectively.