1. A concise synthesis of (S)-N-ethoxycarbonyl-alpha-methylvaline
Jeffrey T Kuethe, Donald R Gauthier Jr, Gregory L Beutner, Nobuyoshi Yasuda J Org Chem. 2007 Sep 14;72(19):7469-72. doi: 10.1021/jo7012862. Epub 2007 Aug 22.
A practical and efficient protocol for the three-step synthesis of (S)-N-ethoxycarbonyl-alpha-methylvaline 3 is described which utilizes readily available commercial starting materials. The key transformations involve resolution-crystallization of tartrate salt 6 followed by a one-pot procedure for the preparation of 3 which is isolated as the dicyclohexylamine salt in 45% overall yield and in 91-95% ee.
2. Fumagillin: an overview of recent scientific advances and their significance for apiculture
Johan P van den Heever, Thomas S Thompson, Jonathan M Curtis, Abdullah Ibrahim, Stephen F Pernal 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.
3. Stability of dicyclohexylamine and fumagillin in honey
Johan P van den Heever, Thomas S Thompson, Jonathan M Curtis, Stephen F Pernal 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.
