Unexpected formation of an oxetane cycle by oxidation of diacetonide of 20-hydroxyecdysone with oxygen in an alkaline medium

9α-hydroxylation of 25-fluoroponasterone a diacetonide in lithium-ammonia solution

“…This interaction induces polarization of the C 14 -O bond thus favoring its hydrolytic cleavage with formation of diol VI. The formation of analogous dimer from 20-hydroxyecdysone diacetonide was confirmed by X-ray analysis [3], though that dimer was stabilized by intermolecular hydrogen bond O 25 -H · · · O 9 /O 14 .…”

“…In the 1 H NMR spectrum of VII in CDCl 3 the 2-H and 3-H signals were displaced upfield by 0.1 and 0.2 ppm, respectively, while the 22-H signal did not change its position (δ 3.6 ppm) relative to that in the spectrum of diacetonide VI. In going from CDCl 3 to CD 3 Repeated hydrolysis of monoacetonide VII did not result in deprotection of the 20-and 22-hydroxy groups, in contrast to nonfluorinated 9α,20-dihydroxyecdysone diacetonide whose hydrolysis smoothly afforded 9α,20-dihydroxyecdysone [9]; the latter is a natural ecdysteroid isolated from Silene italica ssp. nemoralis [10].…”

“…The 13 C NMR spectrum of that mixture contained the following signals, δ C , ppm: 196.8 (C 6 ), 168.4 (C 8 ), 111.0 (C 7 ), 106.7 (C 14 ), 92.7 (C 9 ), which were assigned to epoxy derivative V (cf. [3]). However, we failed to isolate compound V as individual substance; moreover, repeated chromatography gave even more complex mixture whose 13 C NMR spectrum no longer contained signals assignable to V. Obviously, 25-fluoro-substituted derivative V is unstable, which may be due to intermolecular donor-acceptor interaction between the electronegative fluorine atom in one molecule and bridging oxygen atom in the other molecule of dimer A.…”

“…Analogous reactions with ecdysteroids have been poorly studied; however, it is known [3,4] that the reaction of 20-hydroxyecdysone and its acetonides with lithium in liquid ammonia and subsequent treatment with ammonium chloride and evaporation of ammonia on exposure to air gives ecdysteroids with an ether bridge in the C ring instead of expected 7,8-dihydro derivatives. For instance, 20-hydroxyecdysone diacetonide I is thus converted into oxetane II and 14α-hydroperoxide III [3] (Scheme 1).…”

Effective and selective transformations of ecdysteroids into 7,8-dihydro analogs via catalytic hydrogenation under alkaline conditions

“…Attempts to obtain 7,8-dihydro analogs from 20-hydroxyecdysone and its derivatives by reaction with alkali metals in liquid ammonia [2], which is widely used for selective reduction of double bonds in conjugated ketones of the steroid series were unsuccessful [3,4]. Better results were obtained with the use of lithium tetrahydridoaluminate, but the reduction of the C 7 =C 8 double bond was accompanied by reduction of the 6-oxo group [5].…”