Stepwise strategy

A first experiment with a single addition of MnP at the beginning of the operation was carried out in order to determine the enzyme consumption and thus the requirement of enzymatic activity. This feeding rate 37 2 U/(L h) was applied in the following experiments by means of two different strategies stepwise addition (one pulse per hour) or continuous addition [8], The continuous addition of enzyme allowed a high decolorization level (95.7%) with less enzymatic requirements than those of the stepwise addition experiment. An improvement of 69% in terms of efficiency was reached (Table 10.3). 

Our strategy consisted of the following steps A mixture of potential chiral selectors is immobilized on a solid support and packed to afford a complete-library column , which is tested in the resolution of targeted racemic compounds. If some separation is achieved, the column should be deconvoluted to identify the selector possessing the highest selectivity. The deconvolution consisted in the stepwise preparation of a series of sublibrary columns of lower diversity, each of which constitute a CSP with a reduced number of library members. 

As attractive as the transannular bridging of bis(thiolactones) to bicyclic bis(oxepane) frameworks is, our inability to convert the disulfide bridging product (see 25, Scheme 5) to a mmv-fused bre-vetoxin-type bis(oxepane) (see 28) necessitated the development of a modified, stepwise strategy. This new stepwise approach actually comprises two very effective methods for the construction of cyclic ethers the first of these is the intramolecular photo-induced coupling of dithioesters, and the second is the reductive cyclization of hydroxy ketones. We will first address the important features of both cyclization strategies, and then show how the combination of the two can provide an effective solution to the problem posed by trans-fused bis(oxepanes). 

Having developed effective synthetic methodology for the construction of seven-membered cyclic ethers, we were confident that the problem of the frans-fused bis(oxepane) system could now be addressed on a solid foundation. It was our hope that the breve-toxin-type bis(oxepane) system could be assembled by a stepwise strategy utilizing both photochemical dithioester and reductive hydroxy ketone cyclization methods. 

Stepwise Formation of the Bis(oxepane) System The Third-Generation Strategy... 

This is a two-stage probiem that requires a yieid caicuiation and a conversion among molar amounts of products and reactants. This is typicai of yieid caicuiations. Use the percent yield to determine the theoreticai yieid, and then use the stoichiometric ratios to caicuiate masses of starting materials. A flowchart summarizes the stepwise strategy. 

The utility of the stepwise, double-coupling procedure is demonstrated in the parallel synthesis of Tamoxifen derivatives on solid support [127] (Scheme 1-29). 1-Alkenylboronates thus obtained by a diboration-cross coupling sequence are further coupled with p-silyUodobenzene supported on polymer resin. Using this strategy, each position about the ethylene core is modified by the appropriate choice of alkyne, aryl halide, and cleavage conditions for the synthesis of a library of Tamoxifen derivatives. 

Formulate a stepwise monitoring strategy for a hypovolemic shock patient. 

The advantage of iterative strategies is based on the specific preparation of well defined structures and structurally perfect spacers of nanometer scale. This stepwise approach yields monodisperse material in contrast to other statistical routes. The use of the same reactants and the conversion of the same functional groups facilitates the synthetic effort compared with non-iterative methods. 

Coupling of the aminomethylindole 2-558 with acrolein in a Michael manner followed by a HWE reaction with phosphonates 2-560 afforded 2-561 which cyclized under basic conditions to give the desired product 2-566 via the intermediates 2-562-2-565 in 55 % yield (Scheme 2.127). The reaction sequence was also conducted in a stepwise manner, resulting in a greatly reduced yield this clearly demonstrates again the advantage of domino strategies over conventional methods. 

Nitro and 3-amino sugars have been prepared via stepwise construction from acyclic precursors by the nitro-aldol strategy as shown in Scheme 3.8.103... 

Finally in 2005, Hutt and Mander reported their strategy for the synthesis of nominine (Scheme 1.3) [29], The approach relies upon construction of the steroidal ABC carbocyclic ring structure followed by stepwise preparation of the fused aza-ring system. In the key sequence of the synthetic study, enone 50 was oxidized to dienone 51 with DDQ followed by Lewis acid-catalyzed intramolecular conjugate addition of the methylcarbamate to the newly formed dienone to deliver pyrrolidine 52. 

While we were concerned by the potential problems with our desired reaction, particularly the poor dienophilicity of indoles and the failure of 54 to cyclize under stepwise cyclization conditions, we were nonetheless inspired to pursue this potentially direct strategy. The successes of Marko and Rosenmund in related systems (51 —> 52 and 55 —> 56, respectively), the ease of substrate synthesis, and the significant utility of the reaction products compelled us to evaluate Zincke... 

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