42272-94-6Relevant articles and documents
Bishomoisoprenoid triazole bisphosphonates as inhibitors of geranylgeranyl diphosphate synthase
Wills, Veronica S.,Metzger, Joseph I.,Allen, Cheryl,Varney, Michelle L.,Wiemer, David F.,Holstein, Sarah A.
, p. 2437 - 2444 (2017)
Protein geranylgeranylation reactions are dependent on the availability of geranylgeranyl diphosphate (GGDP), which serves as the isoprenoid donor. Inhibition of GGDP synthase (GGDPS) is of interest from a drug development perspective as GGDPS inhibition results in impaired protein geranylgeranylation, which in multiple myeloma, disrupts monoclonal protein trafficking and induces apoptosis. We have recently reported a series of isoprenoid triazole bisphosphonates and have demonstrated that a 3:1 mixture of homogeranyl and homoneryl isomers potently, and in a synergistic manner, inhibits GGDPS. We now present the synthesis and biological evaluation of a novel series of bishomoisoprenoid triazoles which furthers our understanding of the structure-function relationship of this class. These studies demonstrate the importance of chain length and olefin stereochemistry on inhibitory activity.
Further studies of the Daphniphyllum alkaloid polycyclization cascade
Wallace,Heathcock
, p. 450 - 454 (2001)
The scope of the 2-azadiene intramolecular Diels - Alder cyclization, previously employed for synthesis of the Daphniphyllum alkaloids, has been further investigated. Through a series of 1,5-diol cyclization precursors the substitution pattern of both the dienophile and the 2-azadiene were examined. From these studies it was shown that the cascade reaction is tolerant toward a variety of alkyl-substituted dienophiles. However, it was also demonstrated that this reaction is very sensitive to the substitution pattern of the 2-azadiene. Alterations made to the structure of the 2-azadiene cause either competing side reactions or complete failure of the reaction cascade.
AuCl3-Catalyzed Ring-Closing Carbonyl–Olefin Metathesis
Wang, Rui,Chen, Yi,Shu, Mao,Zhao, Wenwen,Tao, Maoling,Du, Chao,Fu, Xiaoya,Li, Ao,Lin, Zhihua
, p. 1941 - 1946 (2020/02/11)
Compared with the ripeness of olefin metathesis, exploration of the construction of carbon–carbon double bonds through the catalytic carbonyl–olefin metathesis reaction remains stagnant and has received scant attention. Herein, a highly efficient AuCl3-catalyzed intramolecular ring-closing carbonyl–olefin metathesis reaction is described. This method features easily accessible starting materials, simple operation, good functional-group tolerance and short reaction times, and provides the target cyclopentenes, polycycles, benzocarbocycles, and N-heterocycle derivatives in good to excellent yields.
Intramolecular [2+2] Photocycloaddition of Cyclic Enones: Selectivity Control by Lewis Acids and Mechanistic Implications
Poplata, Saner,Bauer, Andreas,Storch, Golo,Bach, Thorsten
, p. 8135 - 8148 (2019/05/29)
The intramolecular [2+2] photocycloaddition of 3-alkenyl-2-cycloalkenones was performed in an enantioselective fashion (nine representative examples, 54–86 % yield, 76–96 % ee) upon irradiation at λ=366 nm in the presence of an AlBr3-activated oxazaborolidine as the Lewis acid. An extensive screening of proline-derived oxazaborolidines showed that the enantioface differentiation depends strongly on the nature of the aryl group at the 3-position of the heterocycle. DFT calculations of the Lewis acid–substrate complex indicate that attractive dispersion forces may be responsible for a change of the binding mode. The catalytic [2+2] photocycloaddition was shown to proceed on the triplet hypersurface with a quantum yield of 0.05. The positive effect of Lewis acids on the outcome of a given intramolecular [2+2] photocycloaddition was illustrated by optimizing the key step in a concise total synthesis of the sesquiterpene (±)-italicene.
