Cyclization of Polarized Divinyl Ketones under Aqueous and Ambient Conditions

Abstract

An ‘on‐water’ protocol has been developed for the synthesis of combretastatin A‐4 (CA‐4) analogues by cyclization of polarized triaryldivinyl ketones using hydrochloric acid as a promoter in 45–95% yields. The reaction time was reduced by about 30 times due to ultrasonic irradiation at ambient temperature. The other advantages of this new method are operational simplicity, easy workup, no column purification, and applicability on a gram‐scale. It was shown that the amphiphilicity of the substrate and a low energy barrier of the reaction are a prerequisite for electrophilic and concerted reactions under aqueous and ambient conditions.

Synthesis and crystal structures of D-annulated pentacyclic steroids: looking within and beyond AR signalling in prostate cancer

“…[23][24][25] The development of convenient methods for the chemical modification of steroids is the most important aspect of synthetic organic chemistry, since it expands the applicability of these compounds possessing high biological activity. In continuation of our research to develop new and efficient methods for the preparation of functional compounds, [29][30][31][32][33][34] we have recently designed a novel methodology for the synthesis of pentacyclic steroids of the pregnane series based on readily accessible starting compounds. 35 We have expected that introduction of the fifth fivemembered ring into the steroid system at 16α and 17α positions might increase the antiandrogenic potency of these novel pentacyclic steroids.…”

Photostability and Antiproliferative Activity of Furan Analogues of Combretastatin A-4

“…Recently, in the scope of our research on the development of biologically active compounds − and photosensitive materials, − we synthesized a wide range of new furanone analogues of CA-4 and studied their photochemical properties and antiproliferative activity against A-431 epidermoid carcinoma cells . It was found that, despite their high antiproliferative activity, these compounds underwent photodegradation with activity loss (Chart A).…”

Divergent Reactivity of Triaryldivinyl Ketones: Competing 4π and Putative 6π Electrocyclization Pathways

“…We have recently found that the cyclization of polarized triaryl DVKs I under acidic conditions proceeds via two competitive pathways (Scheme A) . When DVK I bears an electron-deficient substituent, Nazarov cyclization product II is favored, whereas DVKs I with an electron-rich aromatic substituent generate dihydronaphthalenes III preferentially.…”