Alkaloid Strychnos

The list of Strychnos alkaloids (Table II) indicates the following items (1) name, (2) structure, (3) molecular formula, (4) molecular weight, 

18-Deoxy Wieland-Gumlich aldehyde (nordihydrofluoro-curarine) 

A -Deaceiyl-18-hydroxyisoretu- H H H CH2OH OH C19H24N2O2 312 247-250 S. henningsii Gilg. Af 65 

II-Methoxy Wieland-Gumlich H H OMe H OH H C2oH24N20x 340 5. (in olensis Gilg. Af 62 

Wieland-Gumlich aldehyde H H H H OH H CHH22N2i 2 310 5. afz.elii Gilg. Af 85. 91 

The only reported appHcation of to a Strychnos alkaloid that the 

Indoles, Oxindoles, and Related Alkaloids 14.6.3.1 Strychnos Alkaloids 

Members of the strychnos family of alkaloids were among the first compounds to which long-range 2D NMR methods were applied at natural abundance. 

Specifically, strychnine was studied both in the laboratory of one of the authors [33] and in the laboratory of Koshino and coworkers [31]. In addition, brucine (51) and holstiine (52) were studied in the author s laboratory. It is also quite probable that there have been more applications of long-range methods to indole alkaloids 

The chemical shifts of the three alkaloids were quite similar. The N-9 amide shifts were observed toward the downfield end of the normal range for amide i N chemical shifts. The N-19 aliphatic nitrogen shifts were observed in the vicinity of 37 ppm, which is typical of secondary and tertiary aliphatic shifts. Chemical shifts for the three compounds are collected in Table 14.3. 

A complete summary of the long-range coupling pathways of strychnine 

Strychnos nux-vomica (Lx)ganiaceae) is a woody climber that is widely distributed in India, Sri Lanka, and other Asian countries. Its seeds are virulently poisonous and contain as major alkaloids strychnine and brucine, and as minor alkaloids vomicine and novacine. Strychnine is also present in the wood and bark. 

The vomica extract or tincture is made from the seeds and is used as a central nervous system stimulant. Strychnine is an antagonist of barbiturates, and for this reason, the latter are used as antidotes in strychnine poisoning. 

Brucine is a highly toxic alkaloid resembling strychnine and is also used as a central nervous system stimulant. In addition, it is used in analytical chemistry for separating racemic mixtures. These alkaloids possess an additional 2-carbon unit between the indolic Ng and C17. It has been shown that the 2-carbon unit comes from acetate at some stage of the biogenesis (123). 

Strychnos toxifera is a tree that grows wild in the Amazon basins. The stem bark and root bark contain many tertiary or quaternary bis-indole alkaloids such as C-alkaloid A, C-toxiferine I, C-calebassine, caracurine II, caracurine II matho-salt, caracurine V, and nor-dihydrotoxiferine. 

Monomeric tertiary indole alkaloids (diaboline and desacetyldiaboline (Wie-land-Gumlich aldehyde)) and quaternary indole alkaloids (C-hemitoxiferine, C-fluorocurine, C-mavacurine, and macusine A, B, and C) have been also obtained. 

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Of the other Strychnos alkaloids vomicine has been investigated by Ruickoldt, who finds that in mice and rabbits it causes clonic convulsions, due to stimulation above the level of the anterior corpore quad-ragemina. Convulsions can be elicited after intravenous, but not after subcutaneous, injections. The toxicity is low twelve times the convulsive dose does not cause death. No special action is exerted on blood... 

Bonjoch and coworkers have developed a general synthenc entry to strychnos alkaloids of the curan type via a common 3a-f2-nitrophenyl hexahydroindole-4-one intermediate Total synthesis of f- -strychrune Is presented in Scheme 9 5 The first step is based on the S Ar reacdon of o-iodoiritrobenzene v/ith 1,3-cyclohexanone... 

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 intramolecular Heck reaction presented in Scheme 8 is also interesting and worthy of comment. Rawal s potentially general strategy for the stereocontrolled synthesis of the Strychnos alkaloids is predicated on the palladium-mediated intramolecular Heck reaction. In a concise synthesis of ( )-dehydrotubifoline [( )-40],22 Rawal et al. accomplished the conversion of compound 36 to the natural product under the conditions of Jeffery.23 In this ring-forming reaction, the a-alkenylpalladium(n) complex formed in the initial oxidative addition step engages the proximate cyclohexene double bond in a Heck cyclization, affording enamine 39 after syn /2-hydride elimination. The latter substance is a participant in a tautomeric equilibrium with imine ( )-40, which happens to be shifted substantially in favor of ( )-40. 

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,... 

Rosenmund group never applied this reaction to the Strychnos alkaloids (e.g., akuammicine, 58) is somewhat surprising. 

For biogenetic studies of the Strychnos alkaloids, see (a) Bisset NG (1980) In Phillipson JD, Zenk MH (eds) Indole and biogenetically related alkaloids, Academic, London, pp 27-61 (b) Kisakiirek MV, Leeuwenberg AJM, Hesse M (1983) In Pelletier SW (ed) Alkaloids chemical and biological perspectives, vol 1. Wiley, New York, NY, pp 211-376... 

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 ... 

Values of the skeletal complexity metric S for these alkaloids are small, in the range 36-49. In contrast, S/H values are relatively high, in particular for strychnos alkaloids (0.88, Chart 6.1.3.A) this reflects a high molecular complexity that stems from the many cycles and chirality centers, in spite of the low molecular weights. 

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... 

For a closely related example of stereochemical scrambling reported in the synthesis of the Strychnos alkaloid mossambine, see Kuehne, M. E., Wang, T. S., Seraphin, D., J. Org. Chem. 1996,61,7873. 

Bosch J, Bonjoch J and Amat M (1996) The Strychnos alkaloids. The Alkaloids, Chemistry and Pharmacology (ed Cordell GA) Vol 48. Academic, San Diego, pp 75-189. 

Sungucine (193) is a dimeric Strychnos alkaloid of quite a new type which has been isolated from the roots of S. icaja.113 The structure, which was elucidated by X-ray crystallography, is that of a dimer of deoxyisostrychnine, the attachment between the monomer units being via C-5 and C-23. 

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