Allium chemistry: Synthesis, natural occurrence, biological activity, and chemistry of Se-alk(en)ylselenocysteines and their gamma-glutamyl derivatives and oxidation products

Syntheses are reported for gamma -glutamyl Se-methylselenocysteine (8a), se lenolanthionine (16), Se-1-propenylselenocysteine (6d), Se-2-methyl-2-prope nyl-L-selenocysteine (6e), and Se-2-propynyl-L-selenocysteine (6f). Oxidati on of 8a and Se-methylselenocysteine (6a) gives methaneseleninic acid (24), characterized by X-ray crystallography, and dimethyl diselenide (25). Oxid ation of Se-2-propenyl-L-selenocysteine (6c) gives allyl alcohol and 3-sele ninoalanine (22). Compound 22 is also formed on oxidation of 16 and selenoc ystine (4). Oxidation of 6d gives 2-[(E,Z)-1-propenylseleno]-propanal (36). These oxidations occur by way of selenoxides, detected by chromatographic and spectroscopic methods. The natural occurrence of many of the Se-alk(en) ylselenocysteines and their gamma -glutamyl derivatives and oxidation produ cts is discussed. Three homologues of the potent cancer chemoprevention age nts 6a and 6c, namely 6d-f, were evaluated for effects on cell growth, indu ction of apoptosis, and DNA-damaging activity using two murine mammary epit helial cell lines. Although each compound displays a unique profile of acti vity, none of these compounds (6d-f) is likely to exceed the chemopreventiv e efficacy of selenocysteine Se-conjugates 6a and 6c.