Thiarubrines: Novel Dithiacyclohexadiene Polyyne Photosensitizers

Chapter 14

Thiarubrines: Novel Dithiacyclohexadiene Polyyne Photosensitizers from Higher Plants 1

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Shona M . Ellis , Felipe Balza , Peter Constabel , J. B. Hudson , and G. H. Neil Towers

Downloaded by NORTH CAROLINA STATE UNIV on September 10, 2012 | http://pubs.acs.org Publication Date: May 5, 1995 | doi: 10.1021/bk-1995-0616.ch014

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Department of Botany and Department of Pathology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada

The thiarubrines are highly toxic sulfur heterocycles occurring predominantly in resin canals in the cortex and periderm of roots in certain species of Asteraceae. They are readily converted to thiophenes on exposure to light. In addition to light-mediated antiviral, antibacterial, nematocidal, and insecticidal activities they possess activity against fungi which does not require light. They are particularly effective against the human pathogenic yeast, Candida albicans.

Introduction

to

the

Thiarubrines

Polyynes are widely distributed in the Asteraceae. These acetylenic compounds are also commonly found in the Campanulaceae, Apiaceae, Araliaceae as well as in the Basidiomycetes (1). A number of sulfur derivatives including dithiacyclohexadiene polyynes and thiophenes occur exclusively in the Asteraceae primarily in the Heliantheae. The dithiacyclohexadiene polyynes, which we have called thiarubrines (Figure 1), are found in the roots and, in some species e.g. Ambrosia chamissonis, in stems and leaves as well. Chaenactis douglasii and Eriophyltum lanatum produce the positional isomers thiarubrine A, 3-(1-propynyl)-6-(5-hexen-3-yn-1-ynyl)1,2-dithiacyclohexa-3,5-diene and thiarubrine B, 3-(pent-3-yn1-ynyl)-6-(3-buten-1-ynyl)-1,2-dithiacyclohexa-3,5-diene (5). 0097-6156/95/0616-0164$12.00/0 © 1995 American Chemical Society In Light-Activated Pest Control; Heitz, J., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1995.

ELLIS ET AL.

Thiarubrines: Photosensitizers from Higher Plants


14.

Figure

1.

The Chemical

Structures

of the Thiarubrines

In Light-Activated Pest Control; Heitz, J., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1995.

16


166

LIGHT-ACTIVATED PEST CONTROL

Rudbeckia hirta produces geometric isomers of thiarubrine C (22). Table I summarizes the distribution of the thiarubrines throughout the Asteraceae. Ambrosia chamissonis produces the widest array of thiarubrines of any plant analyzed to date (11, 23). Thiarubrines A and B, are usually the major compounds. Other thiarubrines, based on the thiarubrine A skeleton, have been identified. Thiarubrine D, 3-(1-propynyl)-6-(5,6-epoxyhex-3-yn-1-ynyl)1,2-dithiacyclohexa-3,5-diene, and thiarubrine E, 3-(1propynyl)-6-(5,6-dihydroxyhex-3-yn-1-ynyl)-1,2dithiacyclohexa-3,5-diene, a vicinal diol, are unique to this group and in relatively high quantity accompanied by their corresponding thiophenes. Compounds present in lower concentrations include two chlorohydrins, thiarubrines F and G. (3-(1-propynyl)-6-(6-chloro-5-hydroxyhex-3-yn-1-ynyl)-1,2dithiacyclohexa-3,5-diene), a primary alcohol, thiarubrine H, (3(hydroxyprop-1-ynyl)-6-(5-hexen-3-yn-1-ynyl)-1,2dithiacylohex-3,5-diene), and another primary alcohol, thiarubrine I, (3-(1-propynyl)-6-(6-hydroxyhex-3-yn-1-ynyl)1,2-dithiacyclohexadiene) (13) and their corresponding thiophenes. Thiosulphinate J, (3-(1 -propynyl)-6-(5-hexen-3-yn1-ynyl)-cyclohexa-3,5-diene-1,2-thiosulphinate occurs without a corresponding thiophene (12). The thiarubrines are readily converted into thiophenes via ring contraction and sulphur extrusion on irradiation (Figure 2). Thiarubrine A yields the thiophene (2-(1-propynyl)-5-(5-hexen3-yn-1-ynyl)-thiophene) and Β produces the thiophene (2-(pent3-yn-1ynyl)-5-(3-buten-1-ynyl)-thiophene). The thiarubrine solutions becomes yellow upon irradiation because of the presence of elemental sulfur. The thiophenes are colorless. The electronic state of the sulfur has not been established. In Bohlmann's comprehensive book (1) on plant acetylenes UV-visible spectra are presented for a large number of polyynes and much can be gleaned about chromophores of these compounds from these data.

Biosynthesis

There is little known about the biosynthesis of these 13 carbon sulfur compounds although it is clear that they originate from polyynes which, in turn, are known to be derived from fatty acids. Neither the mechanism of triple bond formation nor the biochemical source of the sulfur atoms is known. Tracer studies


14.

ELLIS ET AL.

167 Thiarubrines: Photosensitizers from Higher Plants

by Bohlmann et al.(1) indicate that the terminal carbon of a fatty acid is usually lost in the generation of the odd carbon polyynes. This was corroborated by Gomez-Barrios ef a/. (24) using 3Cacetate in tracer studies. Even though the thiophenes can be produced by irradiation of the corresponding thiarubrine, there appears to be a separate biosynthetic pathway for these two classes of sulfur heterocycles as demonstrated in Chaenactis douglasii using 3 5§ incorporation (25). Bohlmann (1) proposed that the thiarubrines exist in equilibrium with their thioketone isomers which could explain the red coloration. This explanation is not widely accepted (5). The thiarubrines are obviously biosynthetically related and thiarubrine A is probably the precursor of the hydroxylated and chlorinated thiarubrines.


1

hv

+ S

II

Figure 2. Conversion of Thiarubrine Irradiation with UV-A Light.

Isolation,

Purification

and

A to Thiophene A after

Identification

The light sensitive nature of the thiarubrines require that extractions and other chemical manipulations be performed in subdued light (11,12,13). The plant samples are frozen, freeze dried and then ground in a mortar or a Waring blender and extracted with a solvent. The solvent of choice for the non-polar thiarubrines is petroleum ether. When extracting a mixture of non-polar and polar thiarubrines methanohacetonitrile (7:3) is used. HPLC analyses using a preparative MCH-10 (Ci 8* 10mm


LIGHT-ACTIVATED PEST CONTROL

168

Table 1. Distribution of Thiarubrines in the Asteraceae -based on the taxonomy of Bremer (2). Species

Thiarubrine Tribe


Subtribe Mikania

Β Tribe

Helenieae

Β A, Β A L L

(3) (4,5) (4) (6) (6)

A, Β Β A Β L A A A A A

(5) (1) (1) (1) (7) (1 ) (3) (8) (3,9) (3)

Chaenactidinae

Chaenactis douglasii C. glabriuscula Palafoxia hookeriana P. texana Picradeniopsis woodhousei Schkuhria abrotanoides S. advena S. multiflora S. pinnata S. senecioides Tribe Subtribe

(1)

Baeriinae

Eriophyllum caespitosum Ε. lanatum Ε. staechadifolium Lasthenia chrysostoma L coronaria Subtribe

Eupatorieae

Mikaniinae officinalis

Subtribe

Reference

Heliantheae

Ambrosiinae

Ambrosia artemisifolia A. chamissonis

A A, B, D, E, F, G., Η, I, J

(1) (5,10,11, J2,73J


14. ELLIS ET AL.

169 Thiarubrines: Photosensitizers from Higher Plants

Table 1. Continued


Species A. confertiflora A. cumanensis A. eliator A. psilostachya A. trifida A, trifoliata Iva xanthifolia Subtribe

Thiarubrine A

A A A

Α. Κ A A

(Isabel Lopez per. (10) (3) (Isabel Lopez per. (3,14) (3) (3)

Ecliptirtae

A mossambicensis (now placed with the Wedelia group) Β Oyedeae boliviana Β Verbesina alata Β V. boliviana Β V. cinerea V. latisquamata A A V. occidentalis Β Zexmenia hispida

Aspilia

Subtribe

Subtribe

(16) (D (17) (17) (18) (19) (20)

C

Thiarubrines: Novel Dithiacyclohexadiene Polyyne Photosensitizers

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