192460-85-8Relevant articles and documents
Synthesis of Myrocin G, the Putative Active Form of the Myrocin Antitumor Antibiotics
Economou, Christos,Tomanik, Martin,Herzon, Seth B.
, p. 16058 - 16061 (2018)
The antiproliferative antimicrobial fungal metabolites known as the myrocins have been proposed to cross-link DNA by double nucleotide addition. However, the nature of the DNA-reactive species is ambiguous, as myrocins have been isolated as functionally distinct 5-hydroxy-γ-lactone and diosphenol isomers. Based on literature precedent, we hypothesized that the diosphenol 7 (assigned here the trivial name myrocin G) is the biologically active form of the representative isolate (+)-myrocin C (1). To probe this, we developed a short enantioselective route to 7. A powerful fragment-coupling reaction that forms the central ring of the target in 38% yield and in a single step was developed. In support of our hypothesis, 7 was efficiently transformed to the bis(sulfide) 6, a product previously isolated from reactions of 1 with excess benzenethiol. This work provides the first direct access to the diosphenol 7, sets the stage for elucidating the mode of interaction of the myrocins with DNA, and provides a foundation for the synthesis of other pimarane diterpenes.
Chiral amino siloxy dienes in the Diels - Alder reaction: Applications to the asymmetric synthesis of 4-substituted and 4,5-disubstituted cyclohexenones and the total synthesis of (-)-α-elemene
Kozmin, Sergey A.,Rawal, Viresh H.
, p. 9562 - 9573 (2007/10/03)
Described is a study of the preparation, reactivity, and diastereoselectivity of chiral 1-amino-3-siloxy-1,3-butadienes in the Diels - Alder reaction. These dienes were easily prepared in good yield from the corresponding enantiomerically pure substituted pyrrolidines. All the dienes described underwent cycloadditions readily with several activated dienophiles under mild reaction conditions. An amino siloxy diene containing a C2-symmetric 2,5-diphenylpyrrolidine auxiliary was found to provide high diastereofacial control, even at or above room temperature. Upon hydrolysis of the cycloadducts, 4-substituted and 4,5-disubstituted cyclohexenones were obtained with ee's ranging from 85% to >98%. A simple model based primarily on steric arguments was developed to rationalize and predict the absolute configurations of final products obtained by this sequence. The synthetic utility of the methodology was illustrated through a concise enantioselective synthesis of (-)-α-elemene. The synthesis also served to establish the absolute stereochemistry of the Diels-Alder product of the chiral amino siloxy diene and methacrolein.
