Halimane diterpenoids: sources, structures, nomenclature and biological activities

Abstract

Covering: 1970 to 2017 Diterpenes with a halimane skeleton constitute a small group of natural products that can be biogenetically considered as being between labdane and clerodane diterpenoids. Some of these compounds show biological activities, such as antitumour, mosquito repellency, germination inhibition and antimicrobial, as well as being biomarkers for tuberculosis. To the best of our knowledge, there are no reviews on these compounds. In this review, halimane skeleton diterpenoids are classified according to their biogenetic origin, characterization and/or the enzymes involved in their biosynthesis. Herein, a review of their synthesis or synthetic approaches is communicated.

Antibacterial Natural Halimanes: Potential Source of Novel Antibiofilm Agents

“…Halimanes are members of the diterpene family that proceed from geranylgeranyl pyrophosphate and can be considered between labdane and clerodane diterpenes from a biogenetic point of view [22,30]. (Figure 2) Unlike labdane and clerodane diterpenes, more than a milliard compounds of each group are known, but barely 250 halimanes are known.…”

“…ent-Halimic acid, 7, and its acetylderivative [25,30], are the main components of Halimium viscosum (Villarino de los Aires), a plant of the Cistaceae family from which the majority of halimanes have been isolated. Due to this, this diterpene group is named after the gender of Halimium viscosum [22]. ent-Halimic acid, 7, and its acetylderivative, were used as starting materials for the synthesis of chettaphanin I, 5, and chettaphanin II, 6, establishing in 2003 the absolute configuration for the mentioned natural products [31].…”

“…Tuberculosinol, 1, isotuberculosinol, 2, and analogues:1-tuberculosinyl adenosine (1-TbAd), 3, and N 6 -tuberculosinyl adenosine (N 6 -TbAd), 4, are halimanes that could be considered VF of M. tuberculosis and tuberculosis illness [18][19][20][22][23][24][25][26][27][28][29]. Nowadays, these compounds are being tested as biomakers for tuberculosis.…”

Natural Cytotoxic Diterpenoids, a Potential Source of Drug Leads for Melanoma Therapy

“…Halimanes Compounds containing halimane skeleton can be found in different plant species from several families, as well as in marine organisms and microorganism. Biogenetically speaking they are a small group of diterpenes closely related to both labdane and clerodane diterpenoids [1]. One such compound, (5R,8R,9S,13R)-halim-1,10-ene-15,16-diol (27), was isolated from Vellozia kolbekii Alves (Velloziaceae) and showed cytotoxicity against three human cancer cell lines, including MDA-MB-435 by a mechanism of action involving cell cycle arrest at the S/G2M phases [57].…”

“…They have been -together with alkaloids-one of the most successful sources for anticancer drugs. This review focuses on the diterpenes, which arise from geranylgeranyl diphosphate (GGPP) and comprise more than 18,000 different natural compounds presenting 126 different carbon skeletons [1]. Such array of structures and functionalities provides a pool of interesting molecules for therapeutic purpose.…”