Alkaloids Dendrobine

Bicyclic compounds of structure (4) are needed for the synthesis of the alkaloid dendrobine. What is the starting material for a Diels-Alder synthesis of (4) Stereochemistry is obviously vital here. 

The 1,6-diene 254 was prepared from (+)-carvone (253). Its oxidative cyclization affords the zirconacycle 255, and its carbonylation, followed by treatment with iodine and HC1, gave the tricyclic ketone 256 [113]. The alkaloid (—)-dendrobine (257) was synthesized from 256. 

Plants were extracted with CH3OH crystallization removed the main alkaloid (dendrobine), chromatography of the mother liquor yielded... 

Inubushi Y, Kikuchi T, Ibuka T, Tanaka K, Saji I, Tokane K (1972) Total Synthesis of the Alkaloid ( )-Dendrobine. J Chem Soc, Chem Commun 1252... 

Lee CH, Westling M, Livinghouse T, Williams AC (1992) Acybiitrilium Ion Initiated Heteroannulations in Alkaloid Synthesis. An Efficient, Stereocontrolled, Total Synthesis of Orchidaceae Alkaloid ( )-Dendrobine. J Am Chem Soc 114 4089... 

A synthetic approach to the sesquiterpenoid alkaloid, dendrobine (103) has been announced. This involved the formation of the bicyclic ketone (105) by a Diels-Alder reaction of carvotanacetone (104) with butadiene. c/s-Hydroxyla-tion of (105), followed by periodate cleavage and aldolization, led to (106) which was converted into the ketal-ester (107) by standard procedures. Reaction of... 

An -carbonyi radicai cyciization was the key step in C.-K. Sha s enantioselective total synthesis of the alkaloid (-)-dendrobine. The five-membered nitrogen heterocycle was installed during the final stages of the synthetic effort. The bicyclic azido alcohol intermediate was oxidized using the Jones reagent to give the corresponding azido ketone, which was converted in three steps to the natural product. 

Dendrobium findlayanum Sesquiterpenoid Alkaloids Dendrobine (43 R = H) 2-Hydroxydendrobine (43 R = OH) Nobiline (44) 58... 

Similarly, a precursor of the alkaloid dendrobine has been synthesized97. 

Dendrobium Alkaloids.—A possible synthetic route to the alkaloid dendrobine (6 R = H) has been explored. The key reaction in the sequence was the intramolecular... 

The sesquiterpene alkaloid dendrobine (87, Fig. 21.20) also appears formally to be derived from a 2-Z-6- -precur-sor, but is labeled by the , -isomer and not by the 2-Z-6- -compound (Loomis and Croteau, 1980) see sesquiterpene alkaloids Chapter 36). 

The alkaloid dendrobine gives 4-isopropyl-2-pyridone (MI-327) when heated with selenium at 300°. ... 

Similar results have been observed with heteroatomic radicals such as aminyl radical (in an example already discussed in Section VIII.3.A, Scheme 44, and more recently as an important step in the total synthesis of the alkaloid dendrobine ) and with the carboxamidyl radical. The intramolecular addition of thiyl radicals to cyclohexenes generally gives a mixture of the (Cy5) and (Cy6) products. In the same way, intramolecular addition to an unsaturated chain of a thiyl radical on a cyclohexane ring also gives a mixture of (Cy5) and (Cy6) products. This lack of selectivity is in accord with the behavior of unsaturated thiyl radicals discussed in Section VIII.4. An interesting exception of possible relevance to the biosynthetic route to cepham has been discussed in Section VIII.4.B (Scheme 58). The behavior of ethylenic aminothiols such as 107 under free radical initiation (Scheme 52, Section VIII.4.A) has been generalized to compounds such as 267, which affords 268 in 87% yield (Scheme 109). 

Coriamyrtin (4.78), tutin (4.79), picrotoxinin (4.80) (part of the complex metabolite, picrotoxin) and the alkaloid, dendrobine (4.81), are interesting sesquiterpenes which all embrace the structure (4.86). Labelling patterns in (4.78) and (4.79) from [2- C]- and [4- C]-mevalonate and the specific incorporation of labelled copaborneol (4.82, bond broken) indicates the pathway to these compounds... 

One example of the utility of this variation of the reaction can be illustrated in a synthesis of the alkaloid (-)-dendrobine 108. The tricyclic azide 105 was exposed to triphenylphosphine to generate the phosphazene 106 in situ. The intramolecular aza-Wittig then produced 107, an advanced intermediate towards 108. 

A different class of C-N electrophiles was developed by Livinghouse in the total synthesis of the Orchidaceae alkaloid dendrobine (144, Scheme 11.23) [122]. Dendrobine is the principle component of the Chinese folk medicine Chin-Shin-Hu" and has been shown to exhibit antipyretic and hypotensive activity. In this study, it was found that silver-mediated abstraction of the chloride in 141 affords an intermediate acylnitrilium ion 142. This is trapped by the silyl enol ether nucleophile to give bicycle 143 in 88% yield. 

The trimer famesyl pyrophosphate (35), in addition to serving as a pregenitor of steroids via squalene (114), is also the pregenitor of the compounds known as sesquiterpenes. It has been suggested that famesyl pyrophosphate (88) similarly serves as the carbon backbone of alkaloids such as deoxynuphatidine (120) ftom Nupharjapomcum (Nymphaceae) (water hhes) and dendrobine (121) Dendrobium nobikl indl. (Orchidaceae) (Table 11). 

The dopaminergic potential of the Dendrobium species is, to date, open for exploration. An interesting feature of the Dendrobium species is their ability to elaborate sesquiterpene alkaloids, the chemical structure of which resembles the one of strychnine. One such alkaloid is dendrobine, which is widespread in the genus. Kudo et al. noted that dendrobine, isolated from Dendrobium nobile, exhibits a strychnine-like presynaptic inhibition in frog spinal cord (64). 

During the course of a short and efficient total synthesis of (-) -dendrobine (3-76), an alkaloid which exhibits antipyretic and hypotensive activities [37], a new domino radical sequence has been exploited by Cassayre and Zard which involves the cycli-... 

Dendrobine at a dose of 3 X 10-5 M reduced the dorsal root potential and reflex. It provoked a mild hyperpolarization in both dorsal and ventral roots of frog isolated spinal cord. It affected the (3-alanine- and taurine-induced depolarization of primary afferent terminals and reversibly blocked the presynaptic inhibition caused by antidromic conditioning stimulation of the ventral root potential induced by repetitive antidromic stimulation of ventral root and lowered maximum. It would be interesting to learn whether further research of the Dendrobium species discloses any alkaloid interfering with the glycinergic system, an aspect discussed under the following heading. 

Dendrobium Alkaloids.—A third synthesis of shihunine, the principal base of several Dendrobium spp., has been reported. It involves allowing the dilithio-anion (12) to react with l-methyl-2-pyrrolidone (13), to yield ( )-shihunine (14) in 23% yield.11 Full experimental details pertaining to a synthesis of ( )-dendrobine, reported briefly earlier, have been described.12... 

Dendrobium Alkaloids. —An earlier reported synthetic route to (+)-dendrobine has been improved by the development of a superior synthesis of the perhydroindenone intermediate that is involved.13... 

Porter (2) and Coscia (3) described the structures of six dendrobine alkaloids and one dendrobium salt. Although the structures of the dendrobines are less complex than those of most other picrotoxanes, their structure determination became feasible only after spectroscopic methods became generally available in the 1960s. Thus, in 1964, no less than three Japanese research groups completed independently the structure determination of dendrobine (82), the main alkaloid of D. nobile, using a combination of degradation reactions and spectroscopic data analysis (136-138). 

Scheme 11) 81). Mubironine C (99) showed an additional methoxy group and no y-lactone signals. Its structure was proven by its identity with methanolyzed dendrobine. Since all three alkaloids were connected with dendrobine (82) by synthesis, their absolute configuration is in accord with that of dendrobine (82). 

A-Methyldendrobinium chloride (84) was the first quaternary picrotoxane alkaloid isolated and characterized by Inubushi 114). The next dendrobinium salt isolated was A-isopentenyldendrobinium chloride (85) 81). Its structure was determined by pyrolysis to dendrobine (82). The configuration of its quaternary nitrogen was determined by synthesis 81). 

Due to their more simple structures, the syntheses of the sesquiterpene alkaloids, the dendrobines, were mastered first. 

To demonstrate the versatility of his S3mthesis strategy Yamada used ketoester 151 as relais substance to S3mthesize two further picrotoxane alkaloids isolated from Dendrobium species, nobilonine (90) and 2-hydroxydendrobine (87) (Scheme 14) (84). Monobromination of 151 with bromine in dioxane and subsequent treatment with water resulted in hydroxy-y-lactam 152, whereas attempts to hydroxylate 151 by Barton oxidation led to rearrangements. Chemo- and stereoselective reduction with zinc borohydride converted 152 into the en fo-alcohol. To counterbalance the unfavorable conformational equilibrium this alcohol had to be converted into the alcoholate to achieve lactonization. Chemoselective reduction of the hydroxylac-tam moiety of lactone 153 again followed Borch s protocol, which led in this case to boron complexed amino compounds necessitating successive acid treatment to obtain racemic 2-hydroxydendrobine (87) in low yield accompanied by dendrobine (82). 2-Hydroxydendrobine (87) was converted into nobilonine (90) by Eschweiler-Clark methylation. 

Although Dendrobium species are much better known as ornamental plants and for their use in traditional medicine, their alkaloids, the dendrobines, are also convulsants (2). The effects of dendrobinium chloride intoxication resemble more those of strychnine intoxication than those of picrotoxinin intoxication (240). The minimal lethal dose (intravenous) in rats and mice is 20 mg/kg. The toxicity of the picrotoxanes is attributable to their ability to overcome the blood-brain barrier and to bind to inhibitory Cys-loop receptors of the postS3napses of the CNS. 

Hedman K, Leander K (1972) Studies on Orchidaceae Alkaloids XXVII. Quaternary Salts of the Dendrobine Type from Dendrobium nobile Lindl. Acta Chem Scand 26 3177... 

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