Novel route to chaetomellic acid A and analogues: serendipitous discovery of a more competent FTase inhibitor.

A new practical route to chaetomellic acid A (ACA), based on the copper catalysed radical cyclization (RC) of (Z)-3-(2,2-dichloropropanoyl)-2-pentadecylidene-1,3-thiazinane, is described. Remarkably, the process entailed: (i) a one-pot preparation of the intermediate N-α-perchloroacyl-2-(Z)-alkyliden-1,3-thiazinanes starting from N-(3-hydroxypropyl)palmitamide, (ii) a two step smooth transformation of the RC products into ACA and (iii) only one intermediate chromatographic purification step. The method offers a versatile approach to the preparation of ACA analogues, through the synthesis of an intermediate maleic anhydride with a vinylic group at the end of the aliphatic tail, a function that can be transformed through a thiol-ene coupling. Serendipitously, the disodium salt of 2-(9-(butylthio)nonyl)-3-methylmaleic acid, that we prepared as a representative sulfurated ACA analogue, was a more competent FTase inhibitor than ACA. This behaviour was analysed by a molecular docking study.

Ultrastructural Studies of the Effects of Allium sativum on Phytopathogenic Fungi in vitro.

A study was made of the effects of garlic on the development of mycelium in the following phytopathogenic fungi: Fusarium solani (Mart.) Sacc., Rhizoctonia solani Kühn, Pythium ultimum Trow var. ultimum, and Colletotrichum lindemuthianum (Sacc. and Magnus) Briosi and Cav. A suspension of micronized garlic powder, which has volatile organic compounds mainly consisting of linear chain aldehydes, allyl sulfides and disulfides, was used for the trials. Mycelial development of the fungi was strongly inhibited at the maximum concentration of the aqueous extract tested (100 ml/liter); however only the growth of P. ultimum var. ultimum was entirely blocked. Transmission and scanning electron microscopy revealed cytomorphological alterations of the hyphae treated with garlic. R. solani and C. lindemuthianum hyphae appeared especially collapsed, while those of F. solani were less damaged, although thinner than the control hyphae. A general increase in vacuolization was also observed, with consequent reduction in the cytoplasm of the treated fungal cells. R. solani also revealed a thickening of the cell wall, whereas C. lindemuthianum revealed a singular accumulation of osmiophil bodies immediately under the cell membrane.