Gigactonine

Last updated
Gigactonine
Gigactonine.svg
Names
IUPAC name
(1α,6β,14α,16β)-20-Ethyl-4-(hydroxymethyl)-6,14,16-trimethoxyaconitane-1,7,8-triol
Identifiers
3D model (JSmol)
ChemSpider
PubChem CID
  • InChI=1S/C24H39NO7/c1-5-25-10-21(11-26)7-6-15(27)23-13-8-12-14(30-2)9-22(28,16(13)17(12)31-3)24(29,20(23)25)19(32-4)18(21)23/h12-20,26-29H,5-11H2,1-4H3/t12-,13-,14+,15+,16-,17+,18-,19+,20+,21+,22-,23+,24+/m1/s1
    Key: DKODPYKVVJKLFU-YRYTXJGESA-N
  • CCN1C[C@@]2(CC[C@@H]([C@@]34[C@@H]2[C@@H]([C@@](C31)([C@]5(C[C@@H]([C@H]6C[C@@H]4[C@@H]5[C@H]6OC)OC)O)O)OC)O)CO
Properties [1]
C24H39NO7
Molar mass 453.576 g·mol−1
Melting point 168 °C (334 °F; 441 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Gigactonine is a naturally occurring diterpene alkaloid first isolated from Aconitum gigas . It occurs widely in the Ranunculaceae plant family. The polycyclic ring system of this chemical compound contains nineteen carbon atoms and one nitrogen atom, which is the same as in aconitine and this is reflected in its preferred IUPAC name.

Contents

History

Aconitum gigas, from which gigactonine was first isolated Aconitum gigas var. hondoense 01.jpg
Aconitum gigas, from which gigactonine was first isolated

Gigactonine was reported in 1978 after its isolation from Aconitum gigas. Although a novel structure at that time, it was recognised to be related to known diterpene alkaloids including delsoline, which is methylated on its 4-hydroxymethyl primary alcohol sidechain. [1]

Synthesis

Although individual members of this class of alkaloids have been extensively studied, their chemical complexity has limited the number which have been individually synthesised. Similarly, their full biosynthetic pathway is only known in outline in most cases. [2]

Natural occurrence

Gigactonine has been reported as the main alkaloid in the flowers of Aconitum lycoctonum [3] and has been isolated from Delphinium [4] including Delphinium ajacis [5] and other Consolida species in the Ranunculaceae plant family. [6]

Biochemistry

Compounds related to aconitine are widely studied for their properties in biological systems and these have been reviewed. [6] For example, gigactonine has been reported to have hERG-inhibiting activity. [7]

Related Research Articles

<i>Aconitum</i> Genus of flowering plants in the buttercup family Ranunculaceae

Aconitum, also known as aconite, monkshood, wolfsbane, leopard's bane, devil's helmet, or blue rocket, is a genus of over 250 species of flowering plants belonging to the family Ranunculaceae. These herbaceous perennial plants are chiefly native to the mountainous parts of the Northern Hemisphere in North America, Europe, and Asia, growing in the moisture-retentive but well-draining soils of mountain meadows.

<span class="mw-page-title-main">Aconitine</span> Toxic plant alkaloid

Aconitine is an alkaloid toxin produced by various plant species belonging to the genus Aconitum, commonly known by the names wolfsbane and monkshood. Aconitine is notorious for its toxic properties.

<span class="mw-page-title-main">Ranunculaceae</span> Family of eudicot flowering plants

Ranunculaceae is a family of over 2,000 known species of flowering plants in 43 genera, distributed worldwide.

<i>Delphinium</i> Genus of flowering plants

Delphinium is a genus of about 300 species of annual and perennial flowering plants in the family Ranunculaceae, native throughout the Northern Hemisphere and also on the high mountains of tropical Africa. The genus was erected by Carl Linnaeus.

<i>Consolida</i> Genus of flowering plants

Consolida is a genus of about 40 species of annual flowering plants in the family Ranunculaceae, native to western Europe, the Mediterranean and Asia. Phylogenetic studies show that Consolida is actually an annual clade nested within the genus Delphinium and it has been treated as a synonym of Delphinium in Kew's Plants of the World Online. The name of the genus comes from an archaic use of consolidation, meaning "healing", in reference to the plant's medieval use for healing wounds.

<span class="mw-page-title-main">Taxane</span> Chemical compound

Taxanes are a class of diterpenes. They were originally identified from plants of the genus Taxus (yews), and feature a taxadiene core. Paclitaxel (Taxol) and docetaxel (Taxotere) are widely used as chemotherapy agents. Cabazitaxel was FDA approved to treat hormone-refractory prostate cancer.

<i>Consolida regalis</i> Species of plant

Consolida regalis, known as forking larkspur, rocket-larkspur, and field larkspur, is an annual herbaceous plant belonging to the genus Consolida of the buttercup family (Ranunculaceae).

<i>Aconitum lycoctonum</i> Species of plant

Aconitum lycoctonum is a species of flowering plant in the genus Aconitum, of the family Ranunculaceae, native to much of Europe and northern Asia. It is found in lowlands to the subalpine zone, mainly in forests and shaded habitats. Along with A. napellus, A. lycoctonum is of the most common European species of the Aconitum genus. They are also grown ornamentally in gardens, thriving well in ordinary garden soil. As such, A. lycoctonum can be found in North America, especially in eastern Canada, often in old gardens or as garden escapees.

<span class="mw-page-title-main">Voacangine</span> Chemical compound

Voacangine is an alkaloid found predominantly in the root bark of the Voacanga africana tree, as well as in other plants such as Tabernanthe iboga, Tabernaemontana africana, Trachelospermum jasminoides, Tabernaemontana divaricata and Ervatamia yunnanensis. It is an iboga alkaloid which commonly serves as a precursor for the semi-synthesis of ibogaine. It has been demonstrated in animals to have similar anti-addictive properties to ibogaine itself. It also potentiates the effects of barbiturates. Under UV-A and UV-B light its crystals fluoresce blue-green, and it is soluble in ethanol.

<span class="mw-page-title-main">Methyllycaconitine</span> Chemical compound

Methyllycaconitine (MLA) is a diterpenoid alkaloid found in many species of Delphinium (larkspurs). In common with many other diterpenoid alkaloids, it is toxic to animals, although the acute toxicity varies with species. Methyllycaconitine was identified one of the principal toxins in larkspurs responsible for livestock poisoning in the mountain rangelands of North America. Methyllycaconitine has been explored as a possible therapeutic agent for the treatment of spastic paralysis, and it has been shown to have insecticidal properties. It has become an important molecular probe for studying the pharmacology of the nicotinic acetylcholine receptor.

<i>Staphisagria</i> Genus of plants

Staphisagria is a genus in the family Ranunculaceae native to the Mediterranean. It used to be a subgenus or section in the genus Delphinium, but molecular evidence suggests it should be a genus.

<i>Staphisagria macrosperma</i> Species of flowering plant

Staphisagria macrosperma, formerly known as Delphinium staphisagria, is a species of Staphisagria of the family Ranunculaceae. It used to belong to the subgenus or section Staphisagria of the genus Delphinium, but molecular evidence suggests Staphisagria should be a genus which is a sister group to the Aconitum-Delphinium clade. It is described botanically as a stoutly-stemmed, hairy biennial with large palmate leaves up to 6 inches (15 cm) across. The flowers are mauve-blue to blue, short-spurred, and up to 1 inch (2.5 cm) across, occurring in racemes. The plant grows to a height of 4–5 feet. It grows throughout the Mediterranean. All parts of this plant are highly toxic and should not be ingested in any quantity.

<span class="mw-page-title-main">Delphinine</span> Chemical compound

Delphinine is a toxic diterpenoid alkaloid found in plants from the Delphinium (larkspur) and Atragene genera, both in the family Ranunculaceae. Delphinine is the principal alkaloid found in Delphinium staphisagria seeds – at one time, under the name stavesacre, a very well known herbal treatment for body lice. It is related in structure and has similar effects to aconitine, acting as an allosteric modulator of voltage gated sodium channels, and producing low blood pressure, slowed heart rate and abnormal heart rhythms. These effects make it highly poisonous. While it has been used in some alternative medicines, most of the medical community does not recommend using it due to its extreme toxicity.

<span class="mw-page-title-main">Akuammicine</span> Alkaloid

Akuammicine is a monoterpene indole alkaloid of the Vinca sub-group. It is found in the Apocynaceae family of plants including Picralima nitida, Vinca minor and the Aspidosperma.

<span class="mw-page-title-main">Delsoline</span> Naturally occurring chemical compound

Delsoline and delcosine are two closely related naturally occurring diterpene alkaloids first isolated from Delphinium consolida. They occur widely in the Ranunculaceae plant family. The polycyclic ring system containing nineteen carbon atoms and one nitrogen atom in these compounds is the same as in aconitine and this is reflected in their preferred IUPAC name.

<span class="mw-page-title-main">Dideoxyverticillin A</span> Chemical compound

Dideoxyverticillin A, also known as (+)-11,11′-dideoxyverticillin A, is a complex epipolythiodioxopiperazine initially isolated from the marine fungus Penicillium sp. in 1999. It has also been found in the marine fungus Bionectriaceae, and belongs to a class of naturally occurring 2,5-diketopiperazines.

Aconitum flavum is a species of flowering plant in the genus Aconitum of the family Ranunculaceae, native and endemic to northwestern Sichuan, northern Tibet, Qinghai, Gansu, southern Ningxia and southern Inner Mongolia.

<span class="mw-page-title-main">Karel Wiesner</span> Canadian chemist

Karel František Wiesner was a Canadian chemist of Czech origin known for his contributions to the chemistry of natural products, notably aconitum alkaloids and digitalis glycosides.

<span class="mw-page-title-main">Staphidine</span> Staphidine is an alkaloid found in Delphinium species

Staphidine is a bis-diterpene alkaloid of the atisane type, found in the tissues of Delphinium staphisagria in the larkspur family (Ranunculaceae) along with staphimine and staphinine. Similar alkaloids are found in the genus Aconitum in that family, as well as Spiraea in the Rosaceae family.

<span class="mw-page-title-main">Delphinieae</span> Tribe of flowering plants

Delphinieae is a tribe of the subfamily Ranunculoideae of the family Ranunculaceae. It comprises 4 genera found in Eurasia, North America, and Africa.

References

  1. 1 2 Sakai, S.; Shinma, N.; Hasegawa, S.; Okamoto, T. (1978). "On the Alkaloids of Aconitum gigas Lev. et Van. and the structure of a New Base, Gigactonine". Yakugaku Zasshi. 98 (10): 1376–1384. doi: 10.1248/yakushi1947.98.10_1376 .
  2. Cherney, Emily C.; Baran, Phil S. (2011). "Terpenoid-Alkaloids: Their Biosynthetic Twist of Fate and Total Synthesis". Israel Journal of Chemistry. 51 (3–4): 391–405. doi:10.1002/ijch.201100005. PMC   4508874 . PMID   26207071.
  3. Chen, Ying; Katz, Alfred (1999). "Isolation of Norditerpenoid Alkaloids from Flowers of Aconitum lycoctonum". Journal of Natural Products. 62 (5): 798–799. doi:10.1021/np980576q. PMID   10346976.
  4. Yin, Tianpeng; Cai, Le; Ding, Zhongtao (2020). "An overview of the chemical constituents from the genus Delphinium reported in the last four decades". RSC Advances. 10 (23): 13669–13686. doi: 10.1039/D0RA00813C . PMC   9051563 .
  5. Pelletier, S. William; Bhandaru, Sudhakar; Desai, Haridutt K.; Ross, Samir A.; Sayed, Hanna M. (1992). "Two New Norditerpenoid Alkaloids from the Roots of Delphinium ajacis". Journal of Natural Products. 55 (6): 736–743. doi:10.1021/np50084a005.
  6. 1 2 Yin, Tianpeng; Cai, Le; Ding, Zhongtao (2020). "A systematic review on the chemical constituents of the genus Consolida (Ranunculaceae) and their biological activities". RSC Advances. 10 (58): 35072–35089. doi: 10.1039/D0RA06811J . PMC   9056944 .
  7. "Diterpene alkaloids from Aconitum anthora and assessment of the hERG-inhibiting ability of Aconitum alkaloids" (PDF). Planta Med. 77: 368–73. 2011. doi:10.1055/s-0030-1250362. PMID   20862641.