1.Fumagillin: an overview of recent scientific advances and their significance for apiculture.
van den Heever JP1, Thompson TS, Curtis JM, Ibrahim A, Pernal SF. J Agric Food Chem. 2014 Apr 2;62(13):2728-37. doi: 10.1021/jf4055374. Epub 2014 Mar 21.
Fumagillin is a potent fungal metabolite first isolated from Aspergillus fumigatus. It is widely used in apiculture and human medicine against a variety of microsporidian fungal infections. It has been the subject of research in cancer treatments by employing its angiogenesis inhibitory properties. The toxicity of fumagillin has limited its use for human applications and spurred the development of analogues using structure-activity relationships relating to its angiogenesis properties. These discoveries may hold the key to the development of alternative chemical treatments for use in apiculture. The toxicity of fumagillin to humans is important for beekeeping, because any residues remaining in hive products pose a direct risk to the consumer. The analytical methods published to date measure fumagillin and its decomposition products but overlook the dicyclohexylamine counterion of the salt form widely used in apiculture.
2.Asymmetric functional organozinc additions to aldehydes catalyzed by 1,1'-bi-2-naphthols (BINOLs).
Pu L1. Acc Chem Res. 2014 May 20;47(5):1523-35. doi: 10.1021/ar500020k. Epub 2014 Apr 16.
Chiral alcohols are ubiquitous in organic structures. One efficient method to generate chiral alcohols is the catalytic asymmetric addition of a carbon nucleophile to a carbonyl compound since this process produces a C-C bond and a chiral center simultaneously. In comparison with the carbon nucleophiles such as an organolithium or a Grignard reagent, an organozinc reagent possesses the advantages of functional group tolerance and more mild reaction conditions. Catalytic asymmetric reactions of aldehydes with arylzincs, vinylzincs, and alkynylzincs to generate functional chiral alcohols are discussed in this Account. Our laboratory has developed a series of 1,1'-bi-2-naphthol (BINOL)-based chiral catalysts for the asymmetric organozinc addition to aldehydes. It is found that the 3,3'-dianisyl-substituted BINOLs are not only highly enantioselective for the alkylzinc addition to aldehydes, but also highly enantioselective for the diphenylzinc addition to aldehydes.
3.A facile asymmetric approach to the multicyclic core structure of mangicol A.
Ying J1, Pu L. Chemistry. 2014 Dec 1;20(49):16301-7. doi: 10.1002/chem.201404142. Epub 2014 Oct 10.
Chiral propargylic ether-based triene-ynes are synthesized with high enantiomeric purity by employing an asymmetric enyne addition to aldehydes catalyzed by 1,1'-bi-2-naphthol in combination with ZnEt2 , Ti(OiPr)4 and dicyclohexylamine at room temperature. These substrates are found to undergo a one-pot domino Pauson-Khand and Diels-Alder cycloaddition catalyzed by [RhCl(CO)2 ]2 under CO to generate a series of multicyclic products with high chemoselectivity and stereoselectivity. These products contain the multicyclic core structure of mangicol A which could facilitate the synthesis and study of this class of natural products.
4.Stability of dicyclohexylamine and fumagillin in honey.
van den Heever JP1, Thompson TS2, Curtis JM3, Pernal SF4. Food Chem. 2015 Jul 15;179:152-8. doi: 10.1016/j.foodchem.2015.01.111. Epub 2015 Jan 31.
Fumagillin is extensively used to control nosema disease in apiculture. In the commercial formulation, fumagillin is present as a salt in an equimolar quantity with dicyclohexylamine (DCH). In this study DCH was observed to be significantly more resistant to degradation in honey than fumagillin using LC-MS/MS analysis. Observed half-lives for DCH ranged from a minimum of 368 days when kept at 34 °C in darkness, to a maximum of 852 days when stored at 21 °C in darkness. A maximum half-life of 246 days was observed for fumagillin in samples kept in darkness at a temperature of 21 °C. The observed half-life of fumagillin was estimated to be 3 days when exposed to light at 21 °C, and complete decomposition was observed after 30 days under the same conditions. The stability of DCH, combined with its genotoxicity and tumorigenic properties make it an important potential contaminant in honey destined for human consumption.
