Stereochemistry of Diels-Alder Adducts. II. The Alkylation of Some Bicyclic Nitriles

Boehme, Werner R.; Schipper, Edgar; Scharpf, William G.; Nichols, Joseph

doi:10.1021/ja01553a044

Cited by 45 publications

(16 citation statements)

References 3 publications

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“…We suggest that, in the future, the experimental study of the interconversion of these lactones should consider the fact that all of these lactones are chiral and can exist as enantiomers. The endo-and exo-acids can be synthesized 1,4 and, if these acids are not spontaneously interconvertible, then the enantiomers should be separable.…”

Section: Resultsmentioning

confidence: 99%

Molecular mechanics (MM3) study of the lactones ofendo-bicyclo[2.2.2]oct-5-ene-2-carboxylic acid

Kulkarni

Allinger

1999

J. Phys. Org. Chem.

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endo-Bicyclo[2.2.2]oct-5-ene-2-carboxylic acid, in acidic solution, cyclizes to give a mixture of three isomeric lactones. These three isomers have different stabilities and are partly interconvertible, but their simultaneous decomposition makes the experimental study of these equilibria difficult. In the present work, these three lactones were studied using MM3. The relationship between the O-C(O)-C bond angles and the C=O stretching frequencies of these compounds was investigated. Based partly on the thermodynamic data calculated by MM3, the mechanism of the interconversion of the three lactones was proposed.

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Section: Resultsmentioning

confidence: 99%

Molecular mechanics (MM3) study of the lactones ofendo-bicyclo[2.2.2]oct-5-ene-2-carboxylic acid

Kulkarni

Allinger

1999

J. Phys. Org. Chem.

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“…The synthesis of the norbornene-5-exo-carboxylic acid chloride 4 was carried out according to the synthesis protocol published by Boehme et al 26 . The synthesis of aminopropyl-indolenium-bromide 3 was published by the Maiti group 27 .…”

Section: Methodsmentioning

confidence: 99%

NIR-Cyanine Dye Linker: a Promising Candidate for Isochronic Fluorescence Imaging in Molecular Cancer Diagnostics and Therapy Monitoring

Komljenovic¹,

Wießler²,

Waldeck³

et al. 2016

Theranostics

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Personalized anti-cancer medicine is boosted by the recent development of molecular diagnostics and molecularly targeted drugs requiring rapid and efficient ligation routes. Here, we present a novel approach to synthetize a conjugate able to act simultaneously as an imaging and as a chemotherapeutic agent by coupling functional peptides employing solid phase peptide synthesis technologies. Development and the first synthesis of a fluorescent dye with similarity in the polymethine part of the Cy7 molecule whose indolenine-N residues were substituted with a propylene linker are described. Methylating agent temozolomide is functionalized with a tetrazine as a diene component whereas Cy7-cell penetrating peptide conjugate acts as a dienophilic reaction partner for the inverse Diels-Alder click chemistry-mediated ligation route yielding a theranostic conjugate, 3-mercapto-propionic-cyclohexenyl-Cy7-bis-temozolomide-bromide-cell penetrating peptide. Synthesis route described here may facilitate targeted delivery of the therapeutic compound to achieve sufficient local concentrations at the target site or tissue. Its versatility allows a choice of adequate imaging tags applicable in e.g. PET, SPECT, CT, near-infrared imaging, and therapeutic substances including cytotoxic agents. Imaging tags and therapeutics may be simultaneously bound to the conjugate applying click chemistry. Theranostic compound presented here offers a solid basis for a further improvement of cancer management in a precise, patient-specific manner.

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“…Elution with 40% ether-pentane gave 0.4 g (37%) of 10 as a pale yellow solid, mp 63-65 "C. Recrystallization from pentane raised the melting point to 64-65 "C (lit.I3 mp 64-65 "C). 2-exo-Hydroxy-7-an ti-methylbicyclo[ 2.2.11 heptane-7-syncarboxylic Acid y-Lactone (11). The method of Beckmann and Geiger13 was followed.…”

Section: -Endo-hydroxy-2-exo-methyl Bicyclo[ 221 ] Heptane-2-endocmentioning

confidence: 99%

“…While the structure of 2 was rigorously established,8 Risinger et al9 recently challenged this assignment. Subsequently, their erroneous interpretation of NMR data was pointed out by Oxner and Wege.10 The -lactone corresponding to 4 has been claimed by Boehme et al,11 but attempts to repeat this synthesis by us and others have been unsuccessful. 12 One could be misled into assuming that other electrophilic reagents might behave analogously toward 1 and 3 as do iodine or bromine; that is, the endo form yields a 7-lactone while no participation of the carboxyl group occurs in the exo case.…”

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confidence: 99%

Structures of the .gamma.-lactones from the acid-catalyzed cyclization of exo- and endo-2-methylnorbornene-2-carboxylic acid

Moriarty¹,

CHIEN²,

Adams³

1979

J. Org. Chem.

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The structures of the two isomeric y-lactones resulting from acid-catalyzed dehydration of 2-exo-and 2-endomet hylnorbornene-2-carboxylic acids have been proven by chemical degradation to 2,2-dimethylnorbornane and 7,;-dimethylnorbornane. The mechanism of formation of the lactones is discussed, and the implications of these results for related systems are presented.The relatively rigid geometry of the bridged bicyclic norbornyl system and the fixed positions in space of neighboring transannular atoms have caused these compounds to be used for estimation of proximity effects. Since these conformational features are important in enzymatic catalysis, bridged bicyclic compounds have been used as models for various enzyme systems. Recent examples of this strategy have been published by Loudon and Ryono',* and also by Koshland et al.3 One drawback in the use of these compounds as models is the pronounced tendency of the bicyclo[2.2.l]heptyl system to undergo cationic rearrangement. To a lesser extent this is also true of the bicyclo[2.2.2]octyl system. While this aspect of their behavior has led to many fundamental insights into the nature of cationic processes in general, in cases where the occurrence of such changes went unrecognized some serious misassignments of structure have resulted. Recently we reported, in a preliminary way, some examples of such errors in the bicyclo[2.2.l]heptyl* and bicyclo[2.2.2]octyl system^.^ We report now the complete details of the establishment of these structures of rearrangement products in the first system. An accompanying paper deals with the second system. It is interesting to note that these isomers could not be satisfactorily distinguished by means of predominately modern physical methods, and ultimately we had to resort to chemical logic and chemical methods of a more or less classical type.The particular rearrangement, which is the concern of this paper, is that occurring in cation-induced intramolecular lactone formation. A typical example of intramolecular lactone formation is halolactonization,6 which has been widely used as an adjunct to the Diels-Alder reaction of dienophilic carboxylic acidsT for the separation of exo and endo adducts. The method is based upon the valid assumption that only the endo orientation of the carboxyl group in 1 and 3 is correctly articulated in space for intramolecular cyclization with the olefinic double bond to yield a y-lactone.A priori, I arid 3 could yield the six-membered 2,5-lactones, and in fact occ,isionally claims that they do have been made.

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Stereochemistry of Diels-Alder Adducts. II. The Alkylation of Some Bicyclic Nitriles

Cited by 45 publications

References 3 publications

Molecular mechanics (MM3) study of the lactones ofendo-bicyclo[2.2.2]oct-5-ene-2-carboxylic acid

Molecular mechanics (MM3) study of the lactones ofendo-bicyclo[2.2.2]oct-5-ene-2-carboxylic acid

NIR-Cyanine Dye Linker: a Promising Candidate for Isochronic Fluorescence Imaging in Molecular Cancer Diagnostics and Therapy Monitoring

Structures of the .gamma.-lactones from the acid-catalyzed cyclization of exo- and endo-2-methylnorbornene-2-carboxylic acid

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