Strychnos alkaloids strychnine

Strychnos alkaloids Strychnine and brucine Adsorption Silica gel Diethyl ether/ methanol (90 10)... 

Strychnine, the most celebrated member of the Strychnos alkaloids, possesses a complex polycyclic structure which is assembled from only twenty-four skeletal atoms. In addition to its obvious architectural complexity, strychnine s structure contains a contiguous array of six unsymmetrically substituted tetrahedral (asymmetric) carbon atoms of which five are included within one saturated six-membered ring. The intimidating structure of the strychnine molecule elicited the following remark by Sir Robert Robinson in 1952 For its molecular size it is the most complex substance known. 5... 

The convulsant alkaloid strychnine from the Indian tree Strychnos nux vomica is highly toxic. Strychnine... 

Bonjoch and coworkers have developed a general synthetic entry to strychnos alkaloids of the curan type via a common 3a-(2-nitrophenyl)hexahydroindole-4-one intermediate. Total synthesis of (-)-strychnine is presented in Scheme 9.5.20 The first step is based on the SNAr reaction of o-iodonitrobenzene with 1,3-cyclohexanone. 

Scheme 4.1 Oxidative cleavage of an electron-rich aromatic ring was a key component of Woodward s proposal for a biogenesis of the Strychnos alkaloids and a key step in his subsequent synthesis of strychnine...

Another challenge associated with the synthesis of strychnine, as well as other Strychnos alkaloids, is the stereoselective construction of the F-hydroxyethylidene side chain (Scheme 4.5). Strategies that rely on a late-stage olefination reaction of a C20 ketone often suffered from low diasterocontrol for the newly formed alkene, with the best exception provided by Kuehne (15 > 16) [10a, b, d, f]. Overman,... 

Following the application of a Heck cyclization to a concise synthesis of the Strychnos alkaloid dehydrotubifoline [287, 288], and earlier model studies [289], Rawal employed a similar strategy to achieve a remarkably efficient synthesis of strychnine [290]. Thus, pentacycle 277 is smoothly cyclized and deprotected to isostrychnine (278) in 71% overall yield — an appropriate finale to this section ... 

Strychnine (1) is the flagship compound of the family of Strychnos alkaloids and, considering its molecular weight, is one of the most complex natural products.4 Only twenty-four skeletal atoms are... 

The majority of Strychnos alkaloids which are based upon the strychnine skeleton are covered in Chapter 17. 

Among the wide variety of unsaturated functionalities which participate in the cobalt-mediated [2+2+2] cycloaddition that has proved to be a powerful tool for the assembly of complex polycyclic molecules are a number of aromatic heterocyclic double bonds, such as those in pyrrole and indole <20000L2479, 2001JA9324 and references therein>. Indoles, including those substituted at C-3, can be cyclized, both intra- and intermolecularly, with a wide variety of alkynes to yield functionalized products in moderate to good yields. A stereoselective cobalt-mediated [2+2+2] cycloaddition reaction between the W(pent-2-en-4-ynoyl)indole moiety of tryptamine derivative 1093 (R = (CH2)2NHAc) and acetylene has been employed for the formal total synthesis of strychnine 1097, the most famous Strychnos alkaloid and a commonly used rodenticide and animal stimulant (Scheme 213). 

The dried ripe seeds of Strychnos nux-vomica (nux vomica) contain the alkaloids strychnine and brucine, together with traces of other alkaloids. 

Finally, in Rawafs total synthesis of ( )-strychnine, Heck cyclization of vinyl iodide 68 was employed to access the hexacyclic Strychnos alkaloid skeleton and deliver ( -) isostrychnine (69) in 74% yield [25J. Rearrangement in this case would not have been expected since the intermediate formed upon 6-exo closure would contain a particularly unstable tertiary C—Pd bond. The success of the transformation of 68 to 69 in spite of this potential obstacle is noteworthy. 

Of the strychnos alkaloids, mainly strychnine and brucine have been examined by gas chromatography. The gas chromatography has mostly been carried out on non-polar or slightly polar stationary phases (SE-30, SE-52, XE-60, 0V-1 and OV-17), but also more polar liquids... 

American poisonous mixture called curare. Curare is derived from certain members of the genus Strychnos, and contains a number of toxic alkaloids (strychnine being a famihar name for such an alkaloid). Thus, enzymes in glycolysis and the tricarboxylic cycle proper are of fundamental concern, for their blockage or inhibition could prove fatal. Inhibitors for enzymes involved in the carboxylic acid cycle are listed in Appendix B of Hoffman (1999). 

Strychnine, a neurotoxin, is the chief alkaloid present in nux vomica, which is derived from special species of Strychnos, particularly Strychnos nux vomica and Strychnos ignatia. Strychnine is found chiefly in the seeds of these plants, accompanied usually by brucine. Strychnine poisoning causes muscular stiffness, increased reflex reactions, tremors, involuntary twitches, sudden convulsions, and opisthotonus (see Figure 89). 

NMR has become a standard tool for structure determination and, in particular, for these of Strychnos alkaloids. The last general article in this field was authored by J. Sapi and G. Massiot in 1994 [65] and described the advances in spectroscopic methods applied to these molecules. More recently, strychnine (1) has even been used to illustrate newly introduced experiments [66]. We comment, here, on their advantages and sum up the principles of usual 2D experiments in Fig. (1) and Fig. (2) (COSY Correlation SpectroscopY, TOCSY TOtal Correlation SpectroscopY, NOESY Nuclear Overhauser Enhancement SpectroscopY, ROESY Rotating frame Overhauser Enhancement SpectroscopY, HMQC Heteronuclear Multiple Quantum Coherrence, HMBC Heteronuclear Multiple Bond Correlation). This section updates two areas of research in the field new H and 13C NMR experiments with gradient selection or/and selective pulses, 15N NMR, and microspectroscopy. To take these data into account, another section comments on the structure elucidation of new compounds isolated from Strychnos. It covers the literature from 1994 to early 2000. 

The third total synthesis of strychnine (1), so far the only enantioselective route to the natural product, was accomplished by Overman et al. [10] The key to their approach to 1 is the sequential cationic aza-Cope rearran-gement/Mannich cyclization, which is frequently employed with success in alkaloid synthesis. With the synthesis of akuammicine rac-19 the authors proved that this strategy offers an efficient route to the strychnos alkaloids. [8g]... 

A similar strategy was used in Padwa s synthesis of (it)-Strychnine (88) [37], along with other members of the Strychnos alkaloid family [38]. Thus, heating the amidofuran derivative 86 in the presence of catalytic Mgl2 in a microwave reactor (toluene, 150°C, 30 min) afforded the key tetracyclic intermediate 87 in 95% yield (Scheme 24). This intermediate was then used as the main precursor for ( )-Strychnine, ( )-Strychnopivotine, ( )-Tubifolidine, and ( )-Valparicine [38]. 

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