Method Rapoport

Detailed reviews of the chemistry of Hexamine and its nitrolysis to RDX, HMX and other related cyclic and linear polynitramines, including discussions of various postulated reaction mechanisms, are given by Smolin and Rapoport (Ref 9) and by Wright (Ref 15), Methods for the prepn of RDX are also described in Encycl 3, C611 to C615... 

Of the various chemical assays that have been developed for the saxitoxins (75,76), that described by Bates and Rapoport, based on the oxidation of saxitoxin to a fluorescent derivative, has proved to be the most useful. Other assay methods have been developed from it (77-79). The Bates and Rapoport method is virtually insensitive to the N-l-hydroxyl saxitoxins as originally described and so, like the presently available immunoassays, fails as a general assay for either concentration or toxicity. However, it is quite sensitive for those toxins it does detect and has been the basis for other useful methods. 

Analyses for the Saxitoxins. Early methods for analysis of the saxitoxins evolved from those used for toxin isolation and purification. The principal landmarks in the development of preparative separation techniques for the saxitoxins were 1) the employment of carboxylate cation exchange resins by Schantz et al. (82) 2) the use of the polyacrylamide gel Bio-Gel P2 by Buckley and by Shimizu (5,78) and 3) the development by Buckley of an effective TLC system, including a new solvent mixture and a new visualization technique (83). The solvent mixture, designated by Buckley as "E", remains the best for general resolution of the saxitoxins. The visualization method, oxidation of the saxitoxins on silica gel TLC plates to fluorescent degradation products with hydrogen peroxide and heat, is an adaptation of the Bates and Rapoport fluorescence assay for saxitoxin in solution. Curiously, while peroxide oxidation in solution provides little or no response for the N-l-hydroxy saxitoxins, peroxide spray on TLC plates is a sensitive test for all saxitoxin derivatives with the C-12 gemdiol intact. 

With the development of HPLC, a new dimension was added to the tools available for the study of natural products. HPLC is ideally suited to the analysis of non-volatile, sensitive compounds frequently found in biological systems. Unlike other available separation techniques such as TLC and electrophoresis, HPLC methods provide both qualitative and quantitative data and can be easily automated. The basis for the HPLC method for the PSP toxins was established in the late 1970 s when Buckley et al. (2) reported the post-column derivatization of the PSP toxins based on an alkaline oxidation reaction described by Bates and Rapoport (3). Based on this foundation, a series of investigations were conducted to develop a rapid, efficient HPLC method to detect the multiple toxins involved in PSP. Originally, a variety of silica-based, bonded stationary phases were utilized with a low-pressure post-column reaction system (PCRS) (4,5), Later, with improvements in toxin separation mechanisms and the utilization of a high efficiency PCRS, a... 

Detection of the PSP toxins has proven to be one of the largest hurdles in the development of analytical methods. The traditional means, and still in wide use today, is determination of mouse death times for a 1 mL injection of the test solution. There are a variety of drawbacks to utilization of this technique in routine analytical methods, that have prompted the search for replacements. In 1975 Bates and Rapoport (3) reported the development of a fluorescence technique that has proven to be highly selective for the PSP toxins, and very sensitive for many of them. This detection technique has formed the basis for analytical methods involving TLC (77), electrophoresis (72), column chromatography (7J), autoanalyzers (7 ), and HPLC (5,6,7). 

The preparation reported here is based on the method of Christie and Rapoport.4 9-Bromo-9-phenylfluorene has also been prepared by a light-initiated reaction of bromine and 9-phenylfluorene in carbon disulfide,2 by addition of phenylmagnesium bromide to fluorene36 followed by treatment with acetyl bromide,5 and by treatment of 9-phenylfluorene with N-bromosuccinimide.6... 

Kurzchalia, T.V., Wiedmann, M., Breter, H., Zimmermann, W., Bauschke, E., and Rapoport, T.A. (1988) tRNA-mediated labeling of proteins with biotin. A nonradioactive method for the detection of cell-free translation products. Eur. J. Biochem. 172, 663-668. 

Carrera and Sheppard improved upon a Leimgruber-Batcho indole synthesis [24] to prepare 6-bromoindole (20) in excellent overall yield from 4-bromo-2-nitrotoluene [29a], and Rapoport utilized this method to synthesize 4-, 5-, 6-, and 7-bromoindole [29b]. 

Since the PSP toxins lack native fluorescence, useful UV absorption or adequate volatility, more traditional analytical procedures such as gas chromatography or spectrometry have proven ineffective in assaying for the toxins. A number of chemical assays for the toxins have been developed though with the fluorometric method of Bates and Rapoport (3 ) proving to be the most useful to date. This assay is based on oxidation of the PSP toxins under alkaline conditions to fluorescent derivatives. The assay is highly sensitive, fairly specific for the PSP toxins and was incorporated into a detection method in the column chromatographic separation of the toxins described by Buckley et al (4 ). 

Crowley Rapoport J. Org. Chem. 1980, 45, 3215. For another method, see Yamada Ishii Kimura Hosaka Tetrahedron Lett. 1981, 22. 1353. 

D-a-Amino acids. Rapoport et al. have developed a general synthesis of unnatural D-a-amino acids with L-serine as the chiral eduet. The method involves aminoacylation... 

Anatoxin-a is a natnrally occnrring nenrotoxic alkaloid, prodnced by several strains of cyanobacteria. Originally, the species, Anabaena flos aquae, was the sonrce of the toxin, which was conse-qnently named anatoxin-a. Since its isolation (Devlin et al. 1977) and characterisation as a (lA,(5A)-2-acetyl-9-azabicyclo[4.2.1]nonane (Hnber et al. 1972 Koskinen and Rapoport 1985) in the 1970s, anatoxin-a (1 Fig. 7.1 A) has stimnlated the scientific commnnity worldwide. While synthetic chemists devised methods for the constmction of the novel 9-azabicyclo[4.2.1]nonane ring system, medicinal chemists were intrigned by its powerful biological activity. 

Decarbonylation of a-amino acids (7, 292-293). Bates and Rapoport have applied this method for decarbonylation of a -amino acids to the synthesis of the... 

The method was used recently by Bhalerao and Rapoport. Thus a cis-iram mixture of 2,.3-dimcthyl-3-octene (a, b iis-trans ratio 85 15) when heated in a scaled tube at 65°... 

It is understandable that in the early days the x/rr distinction was neglected, because no general method of distinguishing between isomeric N - and N -substituted structures in histidine derivatives was available. It is still the case that this distinction is nontrivial, but the problem has been solved in specific cases by crystallography, chemical degradation, or nuclear Overhauser effect measurements, and no exception to the cross-ring coupling constant criterion of Matthews and Rapoport ° is known. 

Dihydrocodeinone and dihydromorphinone can be prepared by the catalytic rearrangement of codeine [i] and morphine respectively on heating solutions of the base in alcohol, with [48-52] or without [53] acid, with [48-50] or without [51-53] hydrogen, in the presence of noble metal catalysts. The yields reported by Knoll and Co. for this method are up to 95 per cent. [52], but Rapoport claims that the maximum is about 50 per cent. [47]. As a by-product in this rearrangement phenolic bases were noted and these may be made the principal products by modifying the conditions. In this way thebainone-A [xix] can be prepared from codeine, and its analogue, O-desmethylthebainone-A, from morphine in 60 per cent, yield [54] (see Chap. XV). 

For these many reasons, it would be of interest to quantify and image in vivo FA kinetics in brain phospholipids, in animals and in humans. Our laboratory has elaborated a method and model to do this (Rapoport, In press Rapoport et al., 1997 Robinson et al., 1992). 

Operational equations from our FA model have been used to estimate FA fluxes, turnover rates, and half-lives within brain phospholipids in vivo, after values for the dilution factor X of the acyl-CoA pool were experimentally determined. This can be accomplished by a rapid method involving oligonucleotide solid-phase extraction (Deutsch et al., 1997). Low experimental values for X in the awake rat, between 0.02 and 0.04, are consistent with very short half-lives resulting from de-esterificafion-re-esteri-fication of FAs within some phospholipids (minutes to hours), very rapid turnover rates and high ATP consumption (Purdon Rapoport, 1998). 

Robinson PJ, Noronha J, DeGeorge JJ, Freed LM, Nariai T, Rapoport SI. A quantitative method formeasur-ing regional in vivo fatty-acid incorporation into and turnover within brain phospholipids review and critical analysis. Brain Res Reviews 1992 17 187-214. 

Tutwiler GF, Ho W, Mohrbacher RJ. 2-Tetradecylglycidic acid. Methods Enzymol 1981 72 533-551. Washizaki K, Smith QR, Rapoport SI, Purdon AD. Brain arachidonic acid incorporation and precursor... 

The mild reaction conditions of the Corey-Kim oxidation reaction make it an excellent choice when the oxidation of an alcohol that is contained within a complex synthetic intermediate is needed. Rapoport has shown this oxidation method to be useful to prepare aldehydes from primary alcohols in several multi-step syntheses. For example, treatment of alcohol 26 with NCS and DMS in toluene provided aldehyde 27 that was ultimately used to construct the (-)-enantiomer of the C-9-amino acid constituent (28) of immunosuppressant drug cyclosporine as well as the naturally occurring (+)-enantiomer after a slight modification.6... 

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