Flexible Strategies

Thompson, J. D., Gibson, T. J., Plewniak, F., Jeanmougin, F. and Higgins, D. G. The CLUSTAL X windows interface flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res. 25 4876-4882, 1997. 

Total synthesis of complex (macrocyclic) natural products using fast and flexible strategies and diversity-oriented synthesis of natural product-like macrocycles are important research topics in our laboratory. The following sections describe the total synthesis of epothilone D and epothilone D5 analogues, DOS of cyclopeptide alkaloid analogues, of biaryl ether macrocycles, and of steroid/peptide hybrid macrocycles, respectively. 

A phase I/II randomized clinical trial compared ranibizumab injections, given at 4-week intervals, with usual care (control arm) in 64 subjects with predominantly classic or minimally classic AMD. The drug appeared to be effective for both types of AMD as evidenced by improvements in visual acuity at 3 and 6 months and was found to have an acceptable tolerability profile. Subjects with less than 15 letters of acuity at the end of the phase I/II study were followed for over 1 year, but the fixed dosing interval of every 4 weeks was relaxed to a more flexible strategy of holding a dose if acuity was stable (with a change of less than 5 letters) and lesion characteristics were stable on two consecutive visits. Acuity and lesion characteristics continued to be stable in subjects, and the median dosing rate of 1.0 injection every 4 weeks decreased to 0.22 injections every 4 weeks. 

If one is routinely phenotyping a number of GEM strains, it is important to develop an organized, consistent, yet flexible strategy. In general, one only finds what one looks for, so it is desirable to use as comprehensive an approach as possible. On the other hand, every researcher is constrained by economic limitations, so an appropriate balance must be achieved. One widely used approach is to have a core battery of tests that is done on all new knockout strains and then to have flexible batteries of tests that are specific to the project or therapeutic area.19... 

An alternative, flexible strategy for the solid-phase assembly of carbon 3,5-diversi-fied triazoles has recently been demonstrated [92]. As illustrated in Scheme 15, the synthesis pathway possesses sufficient flexibility for the potential introduction of an additional site of diversity at a branch point in either R or R. The nascent... 

An elegant and flexible strategy for the assembly of a synthon for the ort/to-hydroxyaryl-1,3-diketone required for a chromone synthesis depends on the use of an isoxazole as surrogate for the 1,3-diketone unit (25.7). An isoxazole was produced by the cycloaddition (25.12.1.2) of an aryl nitrile oxide to tri-n-butylstannylacetylene, the product coupled with 2,4,6-trihydroxyiodobenzene and then the N-0 bond hydrogenolytically cleaved. ... 

The CLUSTAL X windows interface flexible strategies for multiple sequence alignment aided... 

Marinetti, Voituriez, and coworkers have reported the first diastereo- and enantioselective synthesis of a new family of poly aromatic phosphaheHcene derivatives 64—68, in which the helical sequence ends with either substituted phosphindole or benzophosphindole units (12AGE6748, 14AGE861). The key step of this flexible strategy involves the use of the... 

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