Conformational analysis. LXIX. Improved force field for the calculation of the structures and energies of hydrocarbons

Allinger, Norman L.; Tribble, M. Thomas; Miller, Mary Ann; Wertz, David H.

doi:10.1021/ja00736a012

Cited by 399 publications

(96 citation statements)

References 4 publications

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“…In all cases the Cll-CI2 torsion angle is at or near its maximum and the 11-and 12-substituents are pseudoequatorial. The 6R-PGI, and carbacyclin conformation 6E/"E is the conformational minimum of cis-bicyclo[3.3.0]octane (19,20 For personal use only. The PG12 minimum in Fig.…”

Section: Resultsmentioning

confidence: 99%

The conformations of prostacyclin and related prostaglandins

Beierbeck¹,

Kotovych²,

Sugiura³

1985

Can. J. Chem.

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HELMUT BEIERBECK, GEORGE KOTOVYCH, and MAKIKO SUGIURA. Can. J. Chem. 63, 1 143 (1985). The conformations of prostacyclin, PG12, and three of its analogues, 6R-and 6s-PGII and carbacyclin, were studied by high field 'H nmr spectroscopy. The cis-bicyclo-and cis-oxabicyclo[3.3.O]octane ring conformations were completely assigned. The minima for the pseudorotational conformations are observed at 7~/ l z~ for PGI?, :,T/:~T for 6R-PGI,, and 6 E / 1 '~ for 6s-PGI, and carbacyclin. The data indicate that each molecule adopts a narrow pseudolibrational range, if not a single conformation. The a-and w-side chain conformations were characterized, but not unambiguously. Vicinal coupling constants --and nuclear Overhauser enhancements proved to be the most useful spectroscopic parameters in this study.HELMUT BEIERBECK, GEORGE KOTOVYCH et MAKIKO SUGIURA. Can. J. Chem. 63, 1143Chem. 63, (1985. In a recent series of articles (1-4) we reported ' H nmr chemical shifts and coupling constants for prostacyclin and three of its derivatives, compounds of considerable pharmacological interest. Prostacyclin or PG12, first isolated in 1976, is a potent vasodilator and inhibitor of platelet aggregation (5, 6). It is rather unstable, however, and a number of biologically active analogues were developed ( 3 , among them the isomeric 5,6-dihydroprostacyclins, 6R-PGII and 6s-PGII, and carbacyclin, in which the ether oxygen is replaced by a methylene group. In the present study we have undertaken a detailed conformational analysis, based on ' H nmr coupling constants and nuclear Overhauser effects, of this important group of prostaglandins. ExperimentalThe samples of PGI?, 6s-PGI,, 6R-PGI,, and carbacyclin used in this study were gifts from Drs. R. A. Johnson, J. E. Pike, and D. R. IMorton of Upjohn, Kalamazoo. For the measurements of coupling 'Paper No. 10 in a series of high-field nmr studies on the prostaglandins and leukotrienes.2Author to whom correspondence should be addressed.constants in chloroform solution, CD,OD was distilled into nmr tubes containing PGI? methyl ester or 6s-PGII, respectively, to exchange labile protons; the methanol was then evaporated and CDCI, added. The prostaglandin concentrations were -0.005 M. The samples were sealed after four freeze-pump-thaw cycles. PGIz samples were prepared in glycine/D20 buffer solutions at pH 2 10. Solutions were 0.005 M PGIz in a 0.20 M and 0.015 M buffer and 0.017 M in 0.02 M buffer to check for the effect of concentration on the T , data. The high pH was necessary to prevent PGI? hydrolysis. For 6s-and 6R-PGI,, a 0.10 M phosphate/D20 buffer of pH = 7.0 was used. The samples were weighed into nmr tubes, buffer solution added, the solvent evaporated, fresh 100% D 2 0 added, and oxygen removed in four freeze-pump-thaw cycles. 6s-PGI, concentrations were 0.005 M, 0.008 M, and 0.013 M while the 6R-PGI, solutions were 0.005 M. All glassware was cleaned extensively, including a nitric acid wash, to eliminate paramagnetic impurities.All nmr measurements were carried out on a Bruker WH-40...

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Section: Resultsmentioning

confidence: 99%

The conformations of prostacyclin and related prostaglandins

Beierbeck¹,

Kotovych²,

Sugiura³

1985

Can. J. Chem.

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“…Both contribute to activation energy, the latter owing to the entropic cost of freezing the disordered open chain into the ring-shaped transition state. Strain results principally from imperfect staggering and transannular strain between atoms forced into proximity from opposite sides of the ring, though early force-field calculations on cycloalkanes suggest that bond angle deformation makes a further, smaller contribution [49]. As a cumulative effect of these factors, the activation enthalpy is high for very small lactones (3 members), drops sharply for 4-7 membered lactones, and increases again for medium-sized rings (8-9 members), in which transannular interactions emerge.…”

Section: Model Lactonesmentioning

confidence: 99%

Ruthenium‐Catalyzed Ring‐Closing Metathesis: Recent Advances, Limitations and Opportunities

Conrad

Fogg

2006

ChemInform

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Recent advances in ruthenium-catalyzed ring closing metathesis are discussed, in context of both substrate and catalyst parameters. As well as thermodynamic (substrate) constraints on ring-closing, root causes and effects of non-ideal catalytic performance are examined. Key substrate parameters are outlined, with a particular focus on the balance between oligomerization and ring-closing in RCM macrocyclization reactions. Advances in catalyst design are examined from a mechanistic viewpoint, including initiation requirements, catalyst deactivation, and opportunities resulting from incorporation of pseudohalide ligands. An overview of methods for reducing ruthenium residues in organic products to ppm levels is presented.

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“…Our reference values for angle-bend terms involving C(sp 2) and O are based on experimental results for acetone (Swalen & Costain, 1959;Nelson & Pierce, 1965) and cyclohexanone (Ohnishi & Kozima,I968), and CNDO calculations for cyclohexanone (Fournier, 1975). Corresponding force constants were those obtained by scaling against the parameters of Allinger (Allinger, Tribble, Miller & Wertz, 1971;Allinger, Tribble & Miller, 1972) and Ermer & Lifson (1973).…”

Section: C(sp3)-c(sp 3) Bond Calculation Of Torsional Energy Includementioning

confidence: 99%

What is the favoured conformation of the friedelane skeleton? A combined X-ray and molecular force-field study of friedelin, C₃₀H₅₀O

Mo¹,

Winther²,

Scrimgeour³

1989

Acta Crystallogr Sect B

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Conformational analysis. LXIX. Improved force field for the calculation of the structures and energies of hydrocarbons

Cited by 399 publications

References 4 publications

The conformations of prostacyclin and related prostaglandins

The conformations of prostacyclin and related prostaglandins

Ruthenium‐Catalyzed Ring‐Closing Metathesis: Recent Advances, Limitations and Opportunities

What is the favoured conformation of the friedelane skeleton? A combined X-ray and molecular force-field study of friedelin, C₃₀H₅₀O

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Conformational analysis. LXIX. Improved force field for the calculation of the structures and energies of hydrocarbons

Cited by 399 publications

References 4 publications

The conformations of prostacyclin and related prostaglandins

The conformations of prostacyclin and related prostaglandins

Ruthenium‐Catalyzed Ring‐Closing Metathesis: Recent Advances, Limitations and Opportunities

What is the favoured conformation of the friedelane skeleton? A combined X-ray and molecular force-field study of friedelin, C30H50O

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What is the favoured conformation of the friedelane skeleton? A combined X-ray and molecular force-field study of friedelin, C₃₀H₅₀O