245115-63-3Relevant academic research and scientific papers
Hindered dialkyl ether synthesis with electrogenerated carbocations
Xiang, Jinbao,Shang, Ming,Kawamata, Yu,Lundberg, Helena,Reisberg, Solomon H.,Chen, Miao,Mykhailiuk, Pavel,Beutner, Gregory,Collins, Michael R.,Davies, Alyn,Del Bel, Matthew,Gallego, Gary M.,Spangler, Jillian E.,Starr, Jeremy,Yang, Shouliang,Blackmond, Donna G.,Baran, Phil S.
, p. 398 - 402 (2019/11/05)
Hindered ethers are of high value for various applications; however, they remain an underexplored area of chemical space because they are difficult to synthesize via conventional reactions1,2. Such motifs are highly coveted in medicinal chemistry, because extensive substitution about the ether bond prevents unwanted metabolic processes that can lead to rapid degradation in vivo. Here we report a simple route towards the synthesis of hindered ethers, in which electrochemical oxidation is used to liberate high-energy carbocations from simple carboxylic acids. These reactive carbocation intermediates, which are generated with low electrochemical potentials, capture an alcohol donor under non-acidic conditions; this enables the formation of a range of ethers (more than 80 have been prepared here) that would otherwise be difficult to access. The carbocations can also be intercepted by simple nucleophiles, leading to the formation of hindered alcohols and even alkyl fluorides. This method was evaluated for its ability to circumvent the synthetic bottlenecks encountered in the preparation of 12 chemical scaffolds, leading to higher yields of the required products, in addition to substantial reductions in the number of steps and the amount of labour required to prepare them. The use of molecular probes and the results of kinetic studies support the proposed mechanism and the role of additives under the conditions examined. The reaction manifold that we report here demonstrates the power of electrochemistry to access highly reactive intermediates under mild conditions and, in turn, the substantial improvements in efficiency that can be achieved with these otherwise-inaccessible intermediates.
Total synthesis and revision of stereochemistry of the marine metabolite trunkamide A
Wipf, Peter,Uto, Yoshikazu
, p. 1037 - 1049 (2007/10/03)
The isolation of the cytotoxic Lissoclinum sp. metabolite trunkamide A was reported in 1996. After completion of a total synthesis in 1999, it became clear that the structure of this marine natural product had to be revised. We now report the first preparation of actual trunkamide A in a total synthesis that serves as an unambiguous structural and stereochemical proof. Highlights of our synthetic strategy are a Lewis acid assisted aziridine opening that was used for the preparation of the novel reverse- prenylated serine and threonine side chains as well as an efficient oxazoline-thiazoline interconversion on the macrocyclic skeleton. In addition, several stereoisomers prepared by complementary synthetic protocols serve to illustrate the general scope of our methodology and confirm the configurational assignment.
Total synthesis of the putative structure of the marine metabolite trunkamide A
Wipf, Peter,Uto, Yoshikazu
, p. 5165 - 5169 (2007/10/03)
The structure assigned to trunkamide A, a cycloheptapeptide alkaloid isolated from the colonial ascidian Lissoclinum sp., was prepared via segment condensations and an efficient oxazoline-thiazoline interconversion. The novel reverse prenylated serine and
