Synthesis, Fungitoxic Activity against Botrytis cinerea and Phytotoxicity of Alkoxyclovanols and Alkoxyisocaryolanols

Adriana De Almeida Pinto Bracarense,Maria Amélia Diamantino Boaventura,Jacqueline Aparecida Takahashi,Antonio Ruano-González,Giovanni Gontijo De Souza,Ana A Pinto,Antonio J Macías-Sánchez,Isidro G Collado,Thays Silva Oliveira,Rosa Durán-Patrón,Jociani Ascari

doi:10.3390/jof7121079

Abstract

Clovane and isocaryolane derivatives have been proven to show several levels of activity against the phytopathogenic fungus Botrytis cinerea. Both classes of sesquiterpenes are reminiscent of biosynthetic intermediates of botrydial, a virulence factor of B. cinerea. Further development of both classes of antifungal agent requires exploration of the structure–activity relationships for the antifungal effects on B. cinerea and phytotoxic effects on a model crop. In this paper, we report on the preparation of a series of alkoxy-clovane and -isocaryolane derivatives, some of them described here for the first time (2b, 2d, 2f–2h, and 4c–4e); the evaluation of their antifungal properties against B. cinerea, and their phytotoxic activites on the germination of seeds and the growth of radicles and shoots of Lactuca sativa (lettuce). Both classes of compound show a correlation of antifungal activity with the nature of side chains, with the best activity against B. cinerea for 2d, 2h, 4c and 4d. In general terms, while 2-alkoxyclovan-9-ols (2a–2e) exert a general phytotoxic effect, this is not the case for 2-arylalkoxyclovan-9-ols (2f–2i) and 8-alkoxyisocaryolan-9-ols (4a–4d), where stimulating effects would make them suitable candidates for application to plants.

Highlights

Fungi of the Botrytis (Sclerotiniaceae) genus are involved in substantial crop losses in economically relevant cultivars
In the context of integrated pest management [8], there is an increasing interest in the use of biopesticides [9], which comprises the use of living microorganisms and substances of natural origin, such as plant and microbial extracts, as well as natural products isolated from the abovementioned sources or closely related derivatives
There is a need for the development of novel chemical control agents, capable of being used in conjunction with living microorganisms and with the ability to antagonize B. cinerea, which calls for aiming at selective targets in the fungal infection cycle

Summary

Introduction

Fungi of the Botrytis (Sclerotiniaceae) genus are involved in substantial crop losses in economically relevant cultivars. Clovane and isocaryolane skeleton compounds are caryophyllene cyclization derivatives [35,36], which are reminiscent of botrydial biosynthetic intermediates such as 1(Figure 1) Within this context, 2-alkoxyclovan-9-ols, obtained by the cyclization of caryophyllene oxide in alcohols, catalyzed by TCNE [37], have shown different levels of activity, which are correlated with the nature of the substituent at C-2 [38]. In this paper, we report the preparation of a homologous series of 2alkoxyclovan-9-ols (2a–2e), some related to 2-arylethoxyclovan-9-ols (2f–2i), as well as a homologous series of 8-alkoxyisocaryolan-9-ols (4a–4e) We evaluate their antifungal properties against B. cinerea, and their phytotoxic activities on the germination of seeds and growth of radicles and shoots of L. sativa (lettuce) [44,45,46,47], a plant successfully used in the evaluation of the phytotoxicity of bioactive natural products

General Experimental Procedure

Microorganism and Antifungal Assays

Bioassay for the Germination and Growth of Lettuce Seeds

Results and Discussion