Synthesis of 1-azabicyclo[3.1.0]hexane systems

The synthesis of aziridino[1,2-a]pyrrolidine systems related to the azinomycin family of antitumor agents is reported and was based on an intramolecular addition-elimination reaction sequence. Department of Chemistry, Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210, USA. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1632–1635, December, 1998.     

Synthesis of unsubstituted 1,3,5-triazabicyclo[3.1.0]hexane

Unsubstituted 1,3,5-triazabicyclo[3.1.0]hexane has been syntesized for the first time by treating a Henry solution with NaOCl.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1665–1666, September, 1993.     

Studies on the syntheses of heterocylic compounds—762: Synthesis of 3-benzyl-6-methyl-2-oxo-3,6-diazabicyclo[3.1.0]hexane as a synthetic intermediate of mitomycins

(±)-1-Benzyl-3α-hydroxy-4β-methylamino-2-oxopyrrolidine (15) and its cis-isomer (16) were synthesised from 1-benzyl-4-ethoxycarbonyl-2,3-dioxopyrrolidine (2) in several steps. The former (15) was converted to 3-benzyl-6-methyl-2-oxo-3,6-diazabicyclo[3.1.0]hexane (17) with a mixture of triphenylphosphine, carbon tetrachloride and triethylamine.     

Synthesis of conformationally locked carbocyclic nucleosides built on an oxabicyclo[3.1.0]hexane system

The rigid 6-oxobicyclo[3.1.0]hexane scaffold, characteristic of the natural antibiotic neplanocin C (3), was used to build prototypes of conformationally locked deoxynucleosides in the North hemisphere of the pseudorotational cycle. The purine analogues 6 and 7 are conformationally equivalent to carbocyclic nucleosides built with the bicyclo[3.1.0]hexane template. The pyrimidine nucleosides were unstable and underwent a facile intramolecular epoxide ring-opening reaction leading to heterocycle 22. Only the deoxyguanosine analogue 7 showed antiviral activity against EBV.     

Synthesis of conformationally North-locked pyrimidine nucleosides built on an oxabicyclo[3.1.0]hexane scaffold

Beginning with a known 3-oxabicyclo[3.1.0]hexane scaffold (I), the relocation of the fused cyclopropane ring bond and the shifting of the oxygen atom to an alternative location engendered a new 2-oxabicyclo[3.1.0]hexane template (II) that mimics more closely the tetrahydrofuran ring of conventional nucleosides. The synthesis of this new class of locked nucleosides involved a novel approach that required the isocyanate II (B = NCO) with a hydroxyl-protected scaffold as a pivotal intermediate that was obtained in 11 steps from a known dihydrofuran precursor. The completion of the nucleobases was successfully achieved by quenching the isocyanate with the lithium salts of the corresponding acrylic amides that led to the uracil and thymidine precursors in a single step. Ring closure of these intermediates led to the target, locked nucleosides. The anti-HIV activity of 29 (uridine analogue), 31 (thymidine analogue), and 34 (cytidine analogue) was explored in human osteosarcoma (HOS) cells or modified HOS cells (HOS-313) expressing the herpes simplex virus 1 thymidine kinase (HSV-1 TK). Only the cytidine analogue showed moderate activity in HOS-313 cells, which means that the compounds are not good substrates for the cellular kinases.     

Conformational analysis of 2-phenyl-1,3-diazabicyclo[3.1.0]hexane

The 2-phenyl-1,3-diazabicyclo[3.1.0]hexane molecule was subjected to conformational analysis within the framework of the Westheimer method. The optimum conformations of two of its possible stereoisomers (endo and exo) were found, and the equilibrium concentrations of the latter were calculated and found to be 62 and 38%, respectively. The results of the calculations are in good agreement with the PMR spectroscopic data.     

Acylation of bicyclo[3.1.0]hexane and bicyclo[5.1.0]octane with pivaloyl tetrafluoborate

Conclusions When bicyclo[3.1.0]hexane and bicyclo[5.1.0]octane are acylated with pivaloyl tetrafluoborate the three-membered ring is opened to respectively give 2-methylpivaloylcyclopentane and 2-methylpivaloylcycloheptane derivatives.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2614–2616, November, 1975.     

P-Substituted 3-phosphabicyclo [3.1.0] hexane 3-oxides from diastereoselective substitution at phosphorus

Preparation of P-amino-3-phosphabicyclo[3.1.0]-hexane 3-oxides either by addition of dichlorocarbene to the double bond of 1-amino-2,5-dihydro-1H-phosphole 1-oxides or by substitution of the P-chloro derivative of the bicyclic system was accomplished. Two different diastereomers are obtained by the two approaches; their ¹³C NMR spectra were interpreted on the basis of the P-ethoxy isomers, whose structures were confirmed by X-ray analysis. The P-hydroxy adduct was also prepared, and it was found that intermolecular O H … O hydrogen bonding connects the molecules together in the solid phase. This effect eliminates the possibility of diastereoisomerism, as was also observed in the case of P-hydroxy tetrahydrophosphinine oxides. Thermolysis of the P-hydroxy adduct is a better way to synthesize 1-hydroxy-1,2-dihydrophosphinine oxides than by hydrolysis of the phosphinic chlorides.     

Synthesis of bicyclo[3.1.0]hexane derivatives as conformationally restricted analogues of beta-arabinofuranosyl and alpha-galactofuranosyl rings

A route for the synthesis of bicyclo[3.1.0]hexane-derived conformationally restricted analogues of beta-arabinofuranosyl and alpha-galactofuranosyl rings is described. Advantage is taken of the pseudo-enantiomeric relationship between the two ring systems to develop a route that provides both targets from a single precursor. Key steps include a base-promoted ring contraction of an epoxy ketone obtained from cyclohexane-1,4-dione to give the bicyclo[3.1.0]hexane ring system and a late stage resolution involving esterification with O-acetyl-(S)-mandelic acid.     

The synthesis of a 2-azabicyclo[3.1.0]hexane by rearrangement of a spirocyclic epoxide

An unusual rearrangement of a 1-oxa-6-azaspiro[2.5]octane derivative giving access to novel 5-substituted 2-azabicyclo[3.1.0]hexanes is described. The synthetic application of the reaction is demonstrated by the synthesis of N-Boc-2,3-methano-β-proline. The amino acid was prepared through a three-step synthesis from easily available reagents in an overall yield of 15%.     

First synthesis of 1,5-diazabicyclo[3.1.0]hexane complexes with cadmium salts

Complexes of bicyclic diaziridines 6,6′-bi(1,5-diazabicyclo[3.1.0]hexane) (L ¹ ) and 6-(4-methoxyphenyl)-1,5-diazabicyclo[3.1.0]hexane (L ² ) with the salts Cd(NO₃)₂ · 4H₂O and Cd(ClO₄)₂ · 6H₂O have been synthesized. The fact of complexation has been established by cyclic voltammetry. The crystal structure of complex L ¹ with Cd(NO₃)₂ (the coordination number of cadmium is 8) has been studied by X-ray diffraction.     

三氟甲基侧取代氧、氮、硫杂大环化合物的合成和分子结构

合成了四个三氟甲基侧取代氧、氮、硫杂大环化合物,通过IR、~1H NMR、MS和元素分析作了表征;用AM1方法计算它们的电子结构,并根据计算结果给出了它们的几何构型。     

Synthesis,structure and reactivity of a macrocyclic imine: aza-[13]-macrodiolides

The in situ synthesis and subsequent reactions of macrocylic imine 2 are reported. The imine was trapped with cyanotrimethylsilane to give α-amino nitrile aza-[13]-macrodiolides in a 1:1 ratio of diastereomers. A crystal structure of the syn α-cyano nitrile diastereomer, 7a, provided insights into the lack of selectivity in reactions of 2 relative to macrocyclic alkene 1. Reactions to functionalize the syn diastereomer 7a are also reported.