Absolute Stereochemistry of Antifungal Limonene-1,2-diols from Lippia rubella

Structural properties and evaluation of the antiproliferative activity of limonene‐1,2‐diol obtained by the fungal biotransformation of R‐(+)‐ and S‐(−)‐limonene

“…26 The (+)-(1S,2S,4R)-limonene-1,2-diol seems to be the most common stereoisomers of limonene-1,2-diol in nature. 1,2,8,24 In humans, after oral administration of R-(+)-limonene, (+)-(1S,2S,4R)-limonene-1,2-diol was detected at lower concentrations in both blood and urine. 19 For example, analyses of dichloromethane extract L. rubella (Moldenke) T.R.S.…”

“…Silva & Salimena (Verbenaceae) showed a proportion of around 3:1 between the diastereomers (+)-(1S,2S,4R)-and (À)-(1S,2R,4R)-limonene-1,2-diol. 1 The anticancer effect of R-(+)-limonene has been evaluated in preclinical and clinical studies. [12][13][14][15][16][17]27 Some clinical trials including patients with breast and colon tumors, among others, found promisor beneficial effects of R-(+)-limonene.…”

“…Limonene-1,2-diol is a monoterpenoid that can be naturally found in some plants, such as Lippia rubella, 1 and Pinus koraiensis, 2 and can also be produced by the biotransformation of limonene. [3][4][5][6] Advantages of the last production process include low price and abundance of the substrate (limonene) and possible production of the enantiomerically enriched compounds.…”

“…9 Biological functions already reported for limonene-1,-2-diol include anti-inflammatory, 10 immunomodulatory, 11 and antifungal activities. 1 In terms of anti-cancer potential, several studies were made for its biological precursor, that is, limonene, in several models: in vitro, using different cell lines, 12,13 in vivo, 14,15 and clinical trials. 16,17 These studies indicate that limonene has a well-established chemopreventive action against different cancer types.…”

“…19 However, as far as the authors know, there are no reports dealing with the antiproliferative effect of limonene-1,2-diol, and little is known about the differences in the other biological activities of its optical isomers, such as the antifungal properties of (+)-(1S,2S,4R)-and (À)-(1S,2R,4R)-limonene-1,2-diol. 1 Although limonene-1,2-diol has three chiral centers, thus yielding eight possible stereoisomers (Figure S1), most of the previously mentioned studies focus on the (+)-(1S,2S,4R)-limonene-1,2-diol, which is the only stereoisomer commercially available, the exception being the aforementioned study involving the analysis of (+)-(1S,2S,4R)-and (À)-(1S,2R,4R)-limonene-1,2-diol. 1 Therefore, the present study aimed to identify the limonene-1,2-diol stereoisomers produced by fungal biotransformation of two enantiomers of limonene (biotransformation of R-(+)-or S-(À)-limonene by Colletotrichum nymphaeae and S-(À)-limonene by F. oxysporum 152B) as substrate, followed by a comparative evaluation of the antiproliferative activity in vitro for each product.…”