13934-61-7Relevant academic research and scientific papers
One-Pot γ-Lactonization of Homopropargyl Alcohols via Intramolecular Ketene Trapping
Yamane, Daichi,Tanaka, Haruna,Hirata, Akihiro,Tamura, Yumiko,Takahashi, Daichi,Takahashi, Yusuke,Nagamitsu, Tohru,Ohtawa, Masaki
supporting information, p. 2831 - 2835 (2021/05/05)
A one-pot γ-lactonization of homopropargyl alcohols via an alkyne deprotonation/boronation/oxidation sequence has been developed. Oxidation of the generated alkynyl boronate affords the corresponding ketene intermediate, which is trapped by the adjacent hydroxy group to furnish the γ-lactone. We have optimized the conditions as well as examined the substrate scope and synthetic applications of this efficient one-pot lactonization.
Novel nor-homo-and spiro-oxetan- steroids target the human androgen receptor and act as antiandrogens
Thiele,Rabe,Hessenkemper,Roell,Bartsch,Kraft,Abraham,Houtsmuller,Van Royen,Giannis,Baniahmad
, p. 1156 - 1167 (2015/06/22)
The prostate adenocarcinoma is the cancer with the highest incidence for men in Western countries. Targeting the androgen receptor (AR) by antagonists is used as hormone therapy for prostate cancer (PCa), however, eventually therapy resistance occurs in most patients. In most of these cancer the AR signaling is active and thus AR remains an important drug target. Since many years we are characterizing novel chemical structural platforms to provide a broader possibility for compounds that bind to and act as AR antagonists. Here, we describe the chemical synthesis of a battery of novel steroidal derivatives as nor-homo-, spiro-oxolan- and spiro-oxetan- steroids. They modulate the transcriptional activity of the human AR. As AR antagonists, the spiro-oxetan- steroid derivatives seem to be the most potent steroid derivatives. They inhibit the transcriptional activity of both wild-type AR as well as the AR mutant T877A. In line with this, these compounds bind to the human AR and inhibit the proliferation of the human androgen-dependent growing PCa cell line LNCaP. Interestingly, the castration-resistant AR expressing human PC3-AR cells are also growth inhibited. On mechanistic level, fluorescence resonance energy transfer (FRET) assays with living cells indicate that the androgeninduced N/C terminal interaction of the AR is inhibited by the investigated compounds. Using fluorescence recovery after photobleaching (FRAP) assays in living cells suggest a higher mobility of the AR in the cell nuclei in the presence of spiro-oxetan- steroidal antagonists. Together, these findings suggest that spiro-oxetan- steroids are very useful as a chemical platform for novel AR antagonists.
Ruthenium-catalyzed cycloisomerization - Oxidation of homopropargyl alcohols. A new access to γ-butyrolactones
Trost, Barry M.,Rhee, Young H.
, p. 11680 - 11683 (2007/10/03)
Vinylidenemetal species, which readily form from terminal alkynes under mild conditions, have rarely been utilized as reactive intermediates in a catalytic cycle. The conversion of homopropargyl alcohols via such intermediates to metal-complexed oxacarbenes led to the development of an oxidant compatible with a ruthenium complex capable of performing the cycloisomerization, that would convert them to lactones. None of the oxidants known to stoichiometrically convert isolated metallooxacarbenes to esters are effective. The unconventional oxidants , N-hydroxyimides, proved to be capable of effecting the desired transformation, with N-hydroxysuccinimide being the oxidant of choice. The procedure of choice employs cyclopentadienyl (1,4-cyclooctadiene) ruthenium chloride and trifuryl phosphine as the precatalyst in the presence of tetra-n-butylammonium bromide or hexafluorophosphate with N-hydroxysuccinimide as the oxidant in DMF-water at 95°. In this way, a wide diversity of homopropargyl alcohols were converted to γ-butyrolactones with excellent chemoselectivity. Lactones synthesized include an intermediate toward a platelet aggregation inhibitor, a fruit flavor principle, an inhibitor of binding of phorbol esters to PKC-α, a tobacco constituent, a wood constituent (quercus lactone), an aldosterone antagonist (spironolactone) precursor, and an acetogenin known for pesticidal and antitumor activities (muricatacin).
