The conformations of bicyclo[3.1.0]hexane derivatives by 1H and 13C NMR

The ¹H and ¹³C spectra of bicyclo[3.1.0]hexanes and thujanes have been recorded and assigned. Application of the Karplus equation has yielded dihedral angles, and a computer calculation of the angle of ring buckle as a function of the main dihedral angles has been carried out. The calculated angles of ring buckle agree well with known values in the bicyclo[3.1.0]hexanes, but for 1-methylbicyclo[3.1.0]hexanes and thujanes the results are not self consistent. It is suggested that the bridgehead substituent causes the boat to twist, although the twist can be reduced by an axial methyl substituent on C-4.     

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.     

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.     

TMG catalyzed cyclopropanation of cyclopentenone. Illustration by a simple synthesis of bicyclo[3.1.0]hexane-2-one derivatives

The catalytic preparation of bicyclo[3.1.0]hexane-2-one-6-carboxylic acid ethyl ester 1 is described by cyclopropanation of cyclopentenone using 1,1,3,3-tetramethylguanidine (TMG) as a catalyst in high yield and high diastereoselectivity. This process has been applied to an efficient synthesis of the important intermediate, β-hydroxyl cyclopentanone 2.     

Stereochemistry of terpene derivatives. Part 6: Chemoenzymatic synthesis of chiral bicyclo[3.1.0]hexane derivatives with olfactory properties

Starting from (+)-3-carene 1, several chiral fragrant compounds with the bicyclo[3.1.0]hexane system were synthesized. These compounds were used as substrates for the biotransformation with lipases as biocatalysts. Pure diastereoisomers were obtained and their absolute configuration was confirmed by X-ray crystallography. The olfactory properties of new compounds were determined.     

An efficient route for the construction of cyclopenta[b]quinoline derivatives via intramolecular cyclopropanation

A one-pot process to introduce diazoacetoacetate functionality into quinoline was identified with excellent yield and regioselectivity. An intramolecular cyclopropanation of the resulting adducts gave tetracyclic cyclopenta[b]quinoline derivatives in nearly quantitative yields. A synthetic utility of the tetracyclic derivatives was examined by a simple ring opening reaction to afford cyclopenta[b]quinoline in a good yield.     

Enantioselective synthesis of bicyclo[3.1.0]hexane carbocyclic nucleosides via a lipase-catalyzed asymmetric acetylation. Characterization of an unusual acetal byproduct

The bicyclo[3.1.0]hexane scaffold can lock the conformation of a carbocyclic nucleoside into one of the two antipodal (north or south) conformations typical of conventional nucleosides that normally exist in a rapid, two-state equilibrium in solution. In a recent brief communication, we reported a practical method to access the requisite bicyclo[3.1.0]hexane pseudosugar for the north antipode via an intramolecular olefin-ketocarbene cycloaddition. The most attractive features of this synthesis was that a relatively complex synthon was obtained from simple and inexpensive starting materials and that the resulting racemic mixtures of purine nucleosides could be successfully resolved by adenosine deaminase (ADA) hydrolysis. In this work, we describe the development of a more general, lipase-catalyzed double-acetylation reaction, which could successfully resolve an earlier precursor, 4-(tert-butyldiphenylsilamethoxy)-1-(hydroxymethyl)bicyclo[3.1.0]hexan-2-ol [(+/-)-7], into enantiomerically pure (+)-diacetate 8 and (-)-monoacetate 9. The former diacetate was converted to the conformationally locked (north)-carbocyclic guanosine (+)-17 identical to the one obtained previously by ADA resolution. The present method represents a more general and efficient process applicable to the synthesis of all classes of (north) bicyclo[3.1.0]hexane nucleosides, including pyrimidine analogues. During the lipase-catalyzed resolution, we were able to demonstrate the presence of an unusual acetal-forming reaction that consumed small amounts of the unreactive monoacetate (-)-9. This side reaction was also enzyme-catalyzed and was triggered by the byproduct acetaldehyde generated during the reaction.     

Sculpting the bicyclo[3.1.0]hexane template of carbocyclic nucleosides to improve recognition by herpes thymidine kinase

The replacement of the furanose ring by a cyclopentane in nucleosides generates a group of analogues known generically as carbocyclic nucleosides. These compounds have increased chemical and enzymatic stability due to the absence of a true glycosyl bond that characterizes conventional nucleosides. The additional fusion of a cyclopropane ring to the cyclopentane produces a bicyclo[3.1.0]hexane system that depending on its location relative to the nucleobase is able to lock the embedded cyclopentane ring into conformations that mimic the typical north and south conformations of the furanose ring in conventional nucleosides. These bicyclo[3.1.0]hexane templates have already provided important clues to differentiate the contrasting conformational preferences between kinases and polymerases. Herein, we describe the design, synthesis, and phosphorylation pattern of a new bicyclo[3.1.0]hexane thymidine analogue that seems to possess an ideal spatial distribution of pharmacophores for an optimal interaction with herpes simplex 1 thymidine kinase. The bicyclo[3.1.0]hexane template represents a privileged rigid template for sculpting other carbocyclic nucleosides to meet the demands of specific receptors.     

Substituted azabicyclo[3.1.0]hexan-1-ols from aspartic and glutamic acid derivatives via titanium-mediated cyclopropanation

The Kulinkovich cyclopropanation reaction has been used to synthesize azabicyclo[3.1.0]hexanols from amino acid derivatives containing two ester moieties.     

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.     

Photochemistry of some steroidal bicyclo[3.1.0]hexenones

The photochemistry of five 11-hydroxy-1,5-cyclopregn-3-en-2-ones (‘lumi’ products from the corresponding pregna-1,4-dien-3-ones) has been investigated. In all cases the photoproducts were 1,11-oxy derivatives, resulting from intramolecular attack of the hydroxyl group to the incipient positive charge at C-1. When a fluorine atom was present at C-6, HF elimination took place concurrently with the nucleophilic addition and led to linearly conjugated dienones, rather than the enones obtained in the other cases. Quantum yields were in the range 0.06-0.2, the lower values applying when a fluorine atom was present in position 6 (not in position 9). The results add new evidence on the role of zwitterionic intermediates in the photochemistry of cross-conjugated dienones and the corresponding lumi photoproducts.     

Lewis acid catalyzed reactions of methylenecyclopropylcarbinols with acetals for the construction of 3-oxabicyclo[3.1.0]hexane derivatives

Reactions of methylenecyclopropylcarbinols 1 with acetals 2 in the presence of Lewis acid Sc(OPf)₃ produce the ring-closure products 3-oxabicyclo[3.1.0]hexane in moderate to high total yields along with the products in trans-configuration as the sole or major one. The plausible reaction mechanism has been discussed, which is based on the Prins-type reaction mechanism.     

Studies in bicyclo[3.1.0]hexane methanolysis. Ring opening of activated cyclopropanes under acidic and basic conditions

A bicyclo[3.1.0]hexane, with one cyclopropane carbon flanked by a ketone and an ester or an aldehyde, undergoes methanolysis with cleavage of one of the two activated cyclopropane bonds, depending on the reaction conditions. Acidic conditions yield primarily or exclusively a 4-methoxycyclohexane, while basic conditions yield a 3-methoxymethylcyclopentanone.     

Regiocontrolled synthesis of bicyclo[3.2.1]octane derivatives by cuprate addition and intramolecular acylation

Copper-catalysed reaction of 4-butenylmagnesium bromide with cyclohexenones (2) and (5) occurs with intramolecular acylation of the intermediate enolate to give bicyclo[3.2.1]octane derivatives (4) and (6).     

A direct, efficient method for the preparation of siRNAs containing ribo-like North bicyclo[3.1.0]hexane pseudosugars

An efficient method for the preparation of siRNAs modified with ribo-like North bicyclo[3.1.0]hexane pseudosugars is described. The combined use of 2'-O-(2-cyanoethoxymethyl) (CEM) and 2'-O-TBDMS protection was successfully employed for RNA synthesis with the added advantage that both groups were efficiently removed in a single step. The resulting North ribo-methanocarba-modified siRNAs are compatible with the intracellular RNAi machinery and can mediate specific degradation of target mRNA.     

6-bromo-6-(trimethylstannyl)bicyclo[3.1.0]hexane as a thermal precursor of 1,2-cyclohexadiene

Flash vacuum pyrolysis and matrix-isolation studies of 6-bromo-6-(trimethylstannyl)bicyclo[3.1.0]hexane (1) gave evidence for the formation of 1,2-c.yclohexadiene (2) from this precursor. At high temperatures (600°C) 2 is not stable and fragmentates to 1-butene-3-yne (4) and ethylene.     

级联反应以及双环[2,2,2]辛烯酮的合成

研究了合成桥环化合物1的级联反应,不仅得到已知桥环化合物1,还得到了具有双环[2.2.2]辛烯酮的新桥环化合物2以及两个新的烯丙基取代的呫吨酮3和4。并对可能的反应机理进行了解释。