Diterpenoids

2.3 Diterpenoids

Generally, diterpenoid represent a broad class of non-volatile C_2O compounds that have been essentially obtained from geranyl pyrophosphate.

 

It has been observed that they mostly originate from the plant or fungal sources, but they are invariably formed by certain insects as well as marine organisms.

Characteristic Features Following are some of the characteristic features of diterpenoids, namely:

(a) Most of them are carboxylic compounds having upto five aromatic rings.

(b) Certain members of this class are acyclic compounds,

(c) Mostly occur as hydrocarbons or highly oxygenated compounds based on their degree of oxidation,

(d) Invariably isolated as optically active solids which may occur as the antipodal stereochemical cofigurations and the normal configurations; the former ones are called the ent series, while the latter ones possess and A/B ring fusion and are related to the steroid stereochemically.

A few typical examples of diterpenoids shall be discussed in the sections that follow.

2.3.1 Colforsin

Synonyms Forskolin; Beforsin (obsolete)

Biological Source It is obtained from the root of Coleus forskohlii, Briq., belonging to family Labiatae. The word coleus has been derived from the Greek coleus equivalent to sheath i.e.; the natural formation of the fused filaments of the flower which form a staminal sheath around the style; and the word forskohlii is due to the honour bestowed upon the Finnish botanist Forskal.

Geographical Source The plant is extensively distributed within the subtropical to temperate climatic zones on the hilly regions of Burma, Africa, Nepal, Ceylon and Thailand. It is also found on the dry, sunny slopes of hills at an attitude ranging between 300 to 1800 meters. It is cultivated in India.

Chemical Structure It was first discovered in India during a general sereening studies of potential medicinal plants*. Its chemical name is 7β-acetoxy-8, 13-1α, 6β, 9α-trihydroxylate-14 en-11-one.

 

Uses

1. It is used in the purification of adenylate cyclase; and as a result it serves as a vital research tool in cyclic AMP-related investigations.

2. It also finds enormous use in glaucoma and hypertension.

3. It possesses significant therapeutic potential in diseases like: congestive cardiomyopathy and

bronchial asthma wherein the excessive long term usage of β-adrenergic agonist drugs (e.g.; propranolol, labetalol) ultimately results into the desensitization of the receptors and a loss of drug efficacy.

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* Bhat, S.C. et al., Tetrahedron Letters, 1669, 1977

2.3.2 Ginkgolide–B

Biological Source It is obtained from the root bark and leaves of Ginkgo biloba L., belonging to family Ginkgoaceae.

Geographical Source It is cultivated in the south eastern United States. The priests in China and Japan have confined this specimen to their temple grounds. It is a dioecious tree attaining a maximum height of 30 meters and has been cited in literatures as a living fossil that still survived unchanged in the region of eastern Asia since 200 million years.

Chemical Structure Ginkgolide-B is the most active member of the family significant therapeutic efficacy in the treatment of severe sepsis, whereas the corresponding A and C analogues are devoid of such activities.

Uses

1. The standardized dehydrated acetone–water extract of the dried leaves equivalent to 6% terpenoids and 24% flavone glycosides is sold commercially in Europe as an approved drug to enhance blood fluidity and circulation.

2. In the United States only the tablets containing 40mg of the Ginkgo is allowed to be sold as a ditary suppliment.

3. Ginkgolides A,B, C and M have been shown to check the platelet activating factor (PAF) thereby preventing the bronchoconstriction, hypotension, cutaneous vasodilatation and finally the release of inflammatory compounds.

2.3.3 Taxol

Synonym Paclitaxel; Taxol A; NSC – 125973.

Biological Source It is obtained from the bark of the Pacific Yew tree, Taxus brevifolia Nutt belonging to the family Taxaceae.

Geographical Source The plant is a native to the northwest United States. It is a small, not so growing evergreen tree.

Preparation Keeping in view the paucity of the drug it look quite sometime to isolatetaxol and establish its chemical structure. The very complexity of its chemistry has more or less turned its total synthesis into a not so viable and feasible economic exercise. However, an attempt is being made to enhance its availability through the semisynthetic route whereby the taxol precursors are usually obtained by extraction from the needles of largely available species of Taxus.

Example The chemical component, 10-descetylbaccatin III, isolated from the needles of Taxus baccata Linn., may be conveniently converted to taxol via simple synthetic route.

Note: The needles, in comparison to the bark, may be harvested without causing any injury to the plant whatsoever, and thus provides a rather more easily renewable plant source for the drug.

Chemical Structure The chemical structure is provided below:

Characteristic Features Taxol has the following characteristic features, namely:

(a) It has a taxane ring system,

(b) It has a four membered octane ring

(c) An ester side chain at C-13 of the taxane ring is a prime requirement for taxol’s cytotoxic activity, and

(d) The presence of an accessible hydroxyl moiety at C-2 of the ester side chain renders an appreciable enhancement of the cytotoxic activity.

Uses

1. Taxol is primarily employed in the treatment and management of metastatic carcinoma of the ovarian glands after the failure of follow-up chemotherapy.

2. It is also used in the treatment of breast cancer usually after the observed failure of combination chemotherapy for metastatic disease.

3. Because of its hydrophobic nature the injectable concentrate of taxol formulation meant for

intravenous infusion is normally solubilized duly in polyoxyethylated caster oil. However, before

injection it should be appropriately diluted in normal saline or dextrose solution or combination thereof.

Source:Pharmacognosy And Pharmacobiotechnology By Ashutosh Kar