Chiral diamines 4: a computational study of the enantioselective deprotonation of Boc-pyrrolidine with an alkyllithium in the presence of a chiral diamine.

The enantioselective deprotonation of N-Boc-pyrrolidine (1) with i-PrLi-(-)-sparteine has been studied at theoretical levels up through B3P86/6-31G. Four low-energy intermediate complexes involving i-PrLi-(-)-sparteine and 1 were located via geometry optimizations; two of these complexes would lead to abstraction of the pro-S hydrogen from 1, and the other two complexes would lead to loss of the pro-R hydrogen. The lowest-energy intermediate complex was found to lead to loss of the pro-S hydrogen as observed experimentally. Transition states for the deprotonations were located using the synchronous transit-guided quasi-Newton method. The calculated activation enthalpy for transfer of the pro-S hydrogen within the lowest-energy intermediate complex, 10.8 kcal/mol, is reasonable for a reaction that occurs at a relatively low temperature, and the calculated kinetic hydrogen isotope effect is in agreement with experimental data. The lower enantioselectivity observed experimentally for deprotonation of 1 using t-BuLi-(-)-sparteine is attributed to a transition-state effect due to increased steric interaction engendered by the bulky t-BuLi. Replacement of the tert-butoxycarbonyl group in 1 by a methoxycarbonyl is predicted to result in a slower deprotonation with somewhat decreased enantioselectivity. Asymmetric deprotonation of 1 using i-PrLi in combination with the C(2)-symmetric diamine, (S,S)-1,2-bis(N,N-dimethylamino)cyclohexane, was calculated to be much less selective than is the deprotonation mediated by (-)-sparteine as observed experimentally. The relative energies of the intermediate complexes were fairly well-reproduced by ONIUM calculations in which the sparteine ligand less its nitrogen atoms was treated by molecular mechanics and the remainder of the complex was treated by quantum mechanics.

Cyclization of methyl-substituted 6-heptenyl radicals.

[reaction: see text] The behavior of a series of methyl-substituted 6-heptenyl radicals, generated from the corresponding iodides ((Me(3)Si)(3)SiH, AIBN in benzene at 80 degrees C), has been investigated. The stereoselectivity of the 6-exo cyclizations, affording dimethylcyclohexanes, is low, and sizable quantities of methylcycloheptane, generated via 7-endo cyclization, are also produced.

Grignard reactions of 4-substituted-2-keto-1,3-dioxanes: highly diastereoselective additions controlled by a remote alkyl group.

[see reaction]. The reactions of Grignard reagents with a representative series of simple cis-2-keto-4-substituted-1,3-dioxanes have been investigated. The stereochemical outcome of these highly diastereoselective additions (dr > 90:10) is consonant with Cram's chelate model on the assumption that RMgX coordinates preferentially with the ring oxygen remote from the C(4) substituent.

Solvation and structural effects on the stability of 10-X-2 ate-complexes: a computational study.

The structures and energies of a variety of 10-X-2 ate-complexes derived from reaction of alkyllithiums and aryllithiums with the corresponding organohalides have been studied at the B3LYP/6-31+2G** theoretical level. The results of the calculations, which are in good agreement with the available experimental data, indicate that diaryl ate-complexes are more stable than their dialkyl counterparts. Fluorine substitution was found to confer substantial stability to both diaryl and dialkyl ate-complexes, and the calculations suggest that perfluoro dialkyl 10-X-2 ate-complexes should be experimentally observable species. One of the most important factors contributing to stability of a 10-X-2 ate-complex is removal of the formally cationic lithium from the vicinity of the ate-anion via coordination with a Lewis basic solvent.

Heparin and basic fibroblast growth factor are associated with preservation of latissimus cardiomyoplasties in goats: a retrospective study.

BACKGROUND: Chronic electrical stimulation of cardiomyoplasties often leads to atrophy and fibrosis of the skeletal muscle. In this retrospective study, we re-examined the data in our previous work, which suggested that muscle was preserved by treatment with basic fibroblast growth factor (bFGF). METHODS: Histologic sections were reviewed for evidence of atrophy, and fibrosis from four groups of goats with latissimus dorsi cardiomyoplasty: (1) unstimulated; (2) 2-Hz stimulated x 6 weeks; (3) 2-Hz stimulated with heparin infusion (50 units/hour) x 6 weeks; and (4) 2-Hz stimulated with bFGF (80-micrograms bolus/week) x 6 weeks. RESULTS: Muscle degeneration, as indicated by fat replacement of muscle fibers, was 56.95% +/- 9.16% (mean +/- S.E.) in the 2-Hz stimulated compared with 16.43% +/- 6.22% in unstimulated muscles. In 2-Hz = bFGF and 2 Hz-Heparin (Hep) groups, degeneration was 11.60% +/- 3.04% and 20.36% +/- 5.03%, respectively. bFGF treatment was associated with a greater latissimus blood flow than in the 2-Hz-untreated and 2 Hz-Hep groups (p < 0.05). CONCLUSIONS: bFGF's protection against degeneration may have involved angiogenesis and myogenesis, whereas that of heparin appears to have involved only myogenesis. While the mechanism(s) of the effects of heparin and bFGF remain to be defined, we conclude that they may be a useful adjunct for cardiomyoplasty.

Basic fibroblast growth factor identified in chronically stimulated cardiomyoplasties.

In the presence of myocardial ischemia, chronic electrical stimulation of a latissimus dorsi (LD) cardiomyoplasty enhances extramyocardial collateral blood flow. We postulated that basic fibroblast growth factor (bFGF) may mediate extramyocardial collateral formation. To test this hypothesis, LDs from goats with cardiomyoplasties were probed for the presence of bFGF by Western blot analysis and immunohistochemistry. Three groups were studied: static LD cardiomyoplasty (group 1); LD cardiomyoplasty stimulated at a 2-Hz frequency for 6 weeks (group 2); and LD cardiomyoplasty electrically stimulated and given human recombinant bFGF (group 3). There was no evidence of bFGF in the left LDs of group 1 by Western blot. Basic fibroblast growth factor-like immunoreactive evidence was found in the left LDs of group 2 goats by both Western blot and immunohistochemistry. In the right LDs of group 2, bFGF-like material was found by immunohistochemistry but not by Western blot, which suggests that the tissue concentrations were low (near the limits of detection). The left LDs of group 3 were positive for bFGF by Western blot and immunohistochemistry. Group 3 right LDs were positive for bFGF by immunohistochemistry. Immunohistochemical findings in group 2 indicate that bFGF is present in goat skeletal muscle. Western blot data from groups 1 and 2 suggest that bFGF may be increased in chronically stimulated cardiomyoplasties. From findings in group 3, we conclude that exogenous bFGF does not downregulate, and may upregulate, endogenous production. These results support the possibility that skeletal muscle bFGF is an important factor in extramyocardial collateral formation.

Chronic stimulation enhances extramyocardial collateral blood flow after a cardiomyoplasty.

We have previously demonstrated that collateral blood flow can be established between skeletal muscle and myocardium in animals that have undergone a latissimus dorsi cardiomyoplasty. We have also shown that 5 minutes after the thoracodorsal nerve is electrically stimulated at 1.25 Hz, there is a sixfold increase in the collateral blood flow between the latissimus dorsi and the heart. In this experiment, we hypothesized that chronic stimulation of a latissimus dorsi cardiomyoplasty would result in a sustained increase in the latissimus-derived collateral blood flow. In 24 adult male goats, an ameroid constrictor was placed around a branch of the circumflex coronary artery, and a latissimus dorsi cardiomyoplasty was performed. After a rest period of about 1 week, the latissimus dorsi cardiomyoplasties were stimulated continuously at a 2-Hz frequency for 6 weeks. Collateral blood flow between the muscle and the heart was then measured with colored microspheres. Sixteen animals survived to the final experiment, and collaterals developed in 10. In these 10 animals, the latissimus collaterals continuously delivered 0.17 +/- 0.03 mL.g-1 x min-1 (mean +/- the standard error) of blood to ischemic myocardium. This flow represents 24.0% +/- 3.9% of the flow measured to normal myocardium. These results demonstrate that in an animal model of coronary artery disease, chronic electrical stimulation of a latissimus dorsi cardiomyoplasty maintains an elevated level of latissimus-derived collateral blood flow to the myocardium.

Comparative in vitro sliding-wear study of conventional, microfilled, and light-cured composite restoratives.

The sliding-wear behavior of a number of commercially available microfilled and light-cured composite restoratives has been investigated and compared with the wear characteristics of conventional composites. The surface profiles of the composite restoratives, both pre- and post-test, have also been examined in order to study material attrition processes. The results indicate that: (1) microfilled composites are significantly more resistant to sliding wear than are restoratives containing conventionally-sized filler particles; (2) light-cured, microfilled composites exhibit a lower rate of sliding wear than do self-curing, microfilled restoratives; and (3) the wear process leads to an increase in surface roughness for all materials tested, but microfilled materials display lower surface roughness values, both before and after sliding-wear tests, than do restoratives containing conventional-sized filler particles.

Light diffraction studies of single muscle fibers as a function of fiber rotation.

Light diffraction patterns from single glycerinated frog semitendinosus muscle fibers were examined photographically and photoelectrically as a function of diffraction angle and fiber rotation. The total intensity diffraction pattern indicates that the order maxima change both position and intensity periodically as a function of rotation angle. The total diffracted light, light diffracted above and below the zero-order plane, and light diffracted into individual orders gives information about the fiber's longitudinal and rotational structure and its noncylindrical symmetry.

Wear behavior of a composite restorative and various styli in sliding contact.

Using a pin-on-disc sliding-wear test apparatus, the wear behavior of a typical composite restorative vs. styli fashioned from human enamel, sintered alumina, and magnesium fluoride was examined. The rates of restorative wear were found to be identical, within the experimental error of the measurements, for tests using either human enamel pins or styli fabricated from sintered alumina. Moreover, these two pin materials generated morphologically similar wear-tracks in the restorative disc. Thus, styli of sintered alumina produce restorative wear that is both qualitatively and quantitatively analogous to that observed in tests using human enamel pins.

Influence of contact stress, sliding velocity, and surface roughness on the sliding wear of a composite restorative.

The influence of several experimental parameters on the sliding-wear behavior of a composite restorative has been examined. The results demonstrate that: 1) Changes in surface finish and sliding velocity have little effect on the moderate wear-rate observed at nominal levels of stress, and 2) increased contact stress can profoundly alter wear mechanisms and produce marked surface failure at levels well within the range associated with human mastication.

Influence of variation in contact stress on the sliding-wear behaviour of a dental amalgam.

The influence of variation in contact stress on the sliding-water behaviour of a dispersed amalgam has been investigated. The results demonstrate that: (1) the rate of wear of the amalgam in sliding contact with pins fashioned from human enamel remains virtually constant (0.39 +/- 0.06 micrometer/h-1) throughout the range of stresses encountered in vivo; and (2) the wear process involves adhesive transfer of amalgam to the contacting face of the enamel pin during sliding.