Surrogate effect

While ot,3-unsaturated aldehydes react exclusively with triotganoaluminums in the 1,2-mode, the identical reaction of the corresponding chiral a,3-unsaturated acetals (5), obtained from (RJi)-(+)-N V V V -tetramethyltartaric acid amides, is solvent dependent." For example, in 1,2-dichloroethane, preferential y-addition (Sn2 ) occurs (5 giving 7 Scheme 2), while in dichloromethane, preferential a-addition occurs (5 giving 8 Scheme 2). Subsequent hydrolysis of (7) affords the -substituted aldehydes in high enantiomeric purity (Scheme 2) thus the acetals (5) serve as effective surrogates for —CH=CH—CHO (+CH2CH2CHO). 

Another catalytic application of chiral ketene enolates to [4 + 2]-type cydizations was the discovery of their use in the diastereoselective and enantioselective syntheses of disubstituted thiazinone. Nelson and coworkers described the cyclocondensations of acid chlorides and a-amido sulfones as effective surrogates for asymmetric Mannich addition reactions in the presence of catalytic system composed of O-TM S quinine lc or O-TMS quinidine Id (20mol%), LiC104, and DIPEA. These reactions provided chiral Mannich adducts masked as cis-4,5 -disubstituted thiazinone heterocycles S. It was noteworthy that the in situ formation of enolizable N-thioacyl imine electrophiles, which could be trapped by the nucleophilic ketene enolates, was crucial to the success of this reaction. As summarized in Table 10.2, the cinchona-catalyzed ketene-N-thioacyl-imine cycloadditions were generally effective for a variety of alkyl-substituted ketenes and aliphatic imine electrophiles (>95%ee, >95%cis trans) [12]. 

CsA and equivalent rotamase catalytic activity, indicating that the cysteines play no essential role in binding or catalysis (161). In the case of FKBP, NMR studies of [8,9-[ C]FK-506 bound to recombinant FKBP, wherein the likely mechanism of inhibition also is nonco-valent, suggesting that the a-ketoamide of FK-506 serves as an effective surrogate for the twisted amide of a bound peptide substrate (162). Numerous further NMR, X-ray crystallographic and computational modeling studies have been carried out on both CsA/CyP and FK-506/FKBP complexes to attempt to fully determine a structural basis for activity (163, 164). 

Detailed sampling can include, but is not limited to, the installation of monitoring well networks. After the wells have been installed, aquifer tests are typically performed. Once the aquifer tests are performed and the aquifer characteristics are determined, time series sampling for a given contaminant, or a surrogate, is undertaken. The combined results of these efforts provide the basis for development of a treatment strategy. Modeling can be used as part of this effort to help determine the best technical and most cost-effective techniques to be used at a site. 

At typical indoor concentrations, COj is not thought to be a direct cause of adverse health effects however, COj is an easily-measured surrogate for other occupant-generated pollutants. Eye, nose, and throat irritation headaches lung cancer may contribute to heart disease buildup of fluid in the middle ear increased severity and frequency of asthma episodes decreased lung function. ETS is also a source of odor and irritation complaints. 

Inhaled NO has been used for treatment of persistent pulmonary hypertension of newborn infants, critical respiratory failure of preterm infants, and acute hypertension of adult cardiac surgery patients. PDE-5 inhibitors such as sildenafil are also effective for treatment of pulmonary hypertension. The combination of PDE-5 and NO inhalation yields additive beneficial effects on pulmonary hemodynamics. On the other hand, measurement of exhaled NO is a noninvasive and reproducible test that is a surrogate measure of airway inflammation in patients with bronchial asthma. 

Bir et al." have analyzed the effect of blunt ballistic impact of a baton-type, less-lethal projectile on the thoracic region using human cadavers. She determined human-response corridors and developed biomechanical surrogates, which can be used for testing different new projectiles for their blunt ballistic impact. The human-response force corridor for blunt thoracic impact by a thermoplastic polyurethane-based baton round with 37 mm diameter, weighing 30 g, and traveling... 

---