Williams scheme

Arrhythmias are caused by abnormal pacemaker activity or abnormal impulse propagation. Antiarrhythmic drugs are often classified according to the Vaughan-William scheme, which organizes agents based on channel or receptor involved (Table 2-1). Class I agents block sodium channels and are sometimes referred to as "local anesthetics." The... 

The method is quite effective, but is not widely used now because of the ubiquity of digital computers. Zuman and Patel - 36. show circuit designs for some kinetic schemes. Williams and Bruice made good use of the analog computer in their study of the reduction of pyruvate by 1,5-dihydroflavin. In this simulation eight rate constants were evaluated variations in these parameters of 5% yielded discemibly poorer curve fits. 

Ab-initio studies of surface segregation in alloys are based on the Ising-type Hamiltonian, whose parameters are the effective cluster interactions (ECI). The ECIs for alloy surfaces can be determined by various methods, e.g., by the Connolly-Williams inversion scheme , or by the generalized perturbation method (GPM) . The GPM relies on the force theorem , according to which only the band term is mapped onto the Ising Hamiltonian in the bulk case. The case of macroscopically inhomogeneous systems, like disordered surfaces is more complex. The ECIs can be determined on two levels of sophistication ... 

Williams and Johnston have reported the first use of proton catalysis in the aziridination of imines by diazoesters (Scheme 4.30) [38]. A range of aryl and ali-... 

The kinetics and mechanism of formation of 2,3-naphthotriazole (6.49) were studied by Oh and Williams (1989). In aqueous solutions of 0.2-1.0 m HC104 the dependence of the reaction on acidity indicated simultaneous involvement of the protonated and unprotonated substrates (6.47 and 6.48 respectively). The unproton-ated form of 2,3-diaminonaphthalen (6.48) reacts with the nitrosyl ion (NO+) on encounter (rate constant k ). The 2-NH3 substituent reduces the reactivity of 6.47 by a factor of about 800 (ki/k2). The rate-limiting formation of the diazonium ion (Scheme 6-33) is followed by a rapid cyclization (Scheme 6-34). 

The first total synthesis of the marine dolabellane diterpene (+)-4,5-deoxy-neodolabelline (70) was accomplished by D. R. Williams et al. [58]. The trans-disubstituted dihydropyran moiety in key intermediate 69 was efficiently prepared from mixed acetal 66 by RCM with second-generation catalyst C and subsequent Lewis acid-catalyzed allylation of ethyl glycosides 67 with allylsi-lane 68 (Scheme 12) [59]. 

More recently, Williams has described the one pot synthesis of 2-substituted oxazoles 11 by the thermolysis of triazole amides 9 the reaction does not proceed photo-chemically.<92TL1033> Although the reaction does not involve addition to a nitrile, it is an interesting application of a diazo compound since the proposed zwitterionic intermediate 10 is a resonance form of a diazo imine, so formally the reaction may be thought of as a thermal decomposition of a diazo imine (Scheme 6). 

Whittlesey, Williams and co-workers fnrther developed the catalytic indirect Wittig reaction and fonnd that the more electron-rich NHC present in complex 18 provided a more reactive catalyst [8]. Catalyst 18 was used to convert benzyl alcohol 8 and phosphoninm ylide 19 into the product 20 under slightly milder reaction conditions and in a shorter time than in previous work (Scheme 11.4). Other C-C bond-forming reactions from alcohols using a borrowing hydrogen approach have been reported, with Peris and co-workers using Ir-NHC complexes for the C-3 alkylation of indoles with alcohols [9]. 

In 2004, Whittlesey and Williams demonstrated that the reversible C-H activation of Ru-NHC complexes (e.g. 32a, Scheme 13.14) provides an effective manifold for tandem dehydrogenation/Wittig reaction/hydrogenation of alcohols, thus generating alkanes from alcohols and phosphorus ylides [56]. 

Recently, the same procedure has been used by Williams and coworkers in their approach to the natural product (-)-stemonine (7-18) [10], an alkaloid which exhibits broad biological activity [11]. Conversion of the formyl azide 7-16 in a Staudinger reaction with ethyldiphenylphosphine first generated a phosphineimide which was used for the subsequent aza-Wittig process (Scheme 7.7). The furnished seven-... 

In 2003, Williams and Mander reported a method designed to access the hetisine alkaloids (Scheme 1.3) [27]. This approach, based upon a previously disclosed strategy by Shimizu et al. [28], relied on arylation of a bridgehead carbon via a carbocation intermediate in the key step. Beginning with (1-keto ester 46, double Mannich reaction provided piperidine 47. Following a straightforward sequence, piperidine 47 was transformed to the pivotal bromide intermediate 48. In the key step, bromide 48 was treated with silver (I) 2,4,6-trinitrobenzenesulfonate in nitro-methane (optimized conditions) to provide 49 as the most advanced intermediate of the study, in 54 % yield. 

Williams and Rastetter also accomplished an elegant synthesis of ( )-hyalodendrin (83) in 1980 [39]. Beginning with the sarcosine anhydride-derived enolic aldehyde 78, silyl protection of the enal enabled alkylation of the glycine center with benzyl bromide and thiolation using LDA and monoclinic sulfur a la Schmidt. After protection of the thiol with methylsulfenyl chloride and deprotection of the silyl ether, the enol was sulfenylated with triphenylmethyl chlorodisulfide to afford bis(disulfide) 82 as a 2 1 mixture of diastereomers favoring the anti isomer. Reduction of the disulfides with sodium borohydride and oxidation with KI3 in pyridine afforded ( )-hyalodendrin (83) in 29 % yield (Scheme 9.4). 

The most essential step in a mean-field theory is the reduction of the many-body problem to a scheme that treats just a small number of molecules in an external field. The external field is chosen such that it mimics the effect of the other molecules in the system as accurately as possible. In this review we will discuss the Bragg Williams approach. Here the problem is reduced to behaviour of a single chain (molecule) in an external field. Higher order models (e.g. Quasi-chemical or Bethe approximations) are possible but we do not know applications of this for bilayer membranes. 

Houk, Stoddart and Williams have carried out a detailed investigation (involving experimental and theoretical studies) to quantify the strength of C-H- -O hydrogen bonds in the formation of catenanes [82]. While the formation of the [3]catenane 67 was successful, its conversion to the [4]catenane 68 could not be achieved (see Scheme 32). 

A semiempirical predictor of homoaromaticity has been developed based on the interactions between atoms obtained from an energy partitioning scheme (Williams et al., 1988). This technique correlates the energy lowering two-centre interactions of two non-bonded atoms with homoaromaticity. A second part of the predictor is the demonstration of the necessity of including at least a minimal 2x2 configuration interaction (Cl) treatment. This semiempirical predictor has been verified by correctly interpreting the interactions in cycloheptatriene [5], 1,6-... 

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