18485-76-2Relevant academic research and scientific papers
The synthesis of 4-chloro-17β-hydroxymethyl-17α-methyl-18-norandrosta-4,13-diene-3α-ol – Proposed long term metabolite (M4) of oralturinabol
Beliaev, S. A.,Kozyrkov, Yu. Yu.,Liubina, A. I.,Shostko, D. Yu.
, (2020)
4-Chloro-17β-hydroxymethyl-17α-methyl-18-norandrosta-4,13-diene-3α-ol is one of proposed long term metabolites of oralturinabol (anabolic androgenic steroid restricted in sport). The synthesis of 4-chloro-17β-hydroxymethyl-17α-methyl-18-norandrosta-4,13-diene-3α-ol was achieved. Isomerisation of configuration of 13-carbon was used for construction of 17β-hydroxymethyl-17α-methyl fragment. The proposed route of synthesis allows to obtain 3β-hydroxy isomer as well.
Platinum-Catalyzed α,β-Desaturation of Cyclic Ketones through Direct Metal–Enolate Formation
Chen, Ming,Dong, Guangbin
supporting information, p. 7956 - 7961 (2021/03/01)
The development of a platinum-catalyzed desaturation of cyclic ketones to their conjugated α,β-unsaturated counterparts is reported in this full article. A unique diene-platinum complex was identified to be an efficient catalyst, which enables direct metal-enolate formation. The reaction operates under mild conditions without using strong bases or acids. Good to excellent yields can be achieved for diverse and complex scaffolds. A wide range of functional groups, including those sensitive to acids, bases/nucleophiles, or palladium species, are tolerated, which represents a distinct feature from other known desaturation methods. Mechanistically, this platinum catalysis exhibits a fast and reversible α-deprotonation followed by a rate-determining β-hydrogen elimination process, which is different from the prior Pd-catalyzed desaturation method. Promising preliminary enantioselective desaturation using a chiral-diene-platinum complex has also been obtained.
Synthesis and structural elucidation of a dehydrochloromethyltestosterone metabolite
Kratena, Nicolas,Pilz, Sarah M.,Weil, Matthias,Gmeiner, Günter,Enev, Valentin S.,G?rtner, Peter
, p. 2508 - 2521 (2018/04/12)
The human urinary long-term metabolite "M3" (4-chloro-17β-hydroxymethyl-17α-methyl-18-norandrost-13-en-3-ol) of the common doping agent DHCMT has thus far been detected via GC/MS-MS, creating ambiguities concerning its absolute configuration. Its structure was elucidated via the synthesis of all eight possible stereoisomers with 17β-hydroxymethyl configuration. The highlights of the synthesis consist of a novel first generation approach to 4β-chloro-5β compounds as well as a divergent route which allows easy access to the remaining A-ring chlorohydrins.
A FACILE SYNTHESIS OF STEROIDAL Δ4-3-KETONES USING PYRIDINIUM CHLOROCHROMATE (PCC)
Parish, Edward J.,Honda, Hiroshi
, p. 1167 - 1174 (2007/10/02)
Pyridinium chlorochromate (PCC), in refluxing benzene, has been found to be an affective and convenient reagent for the oxidation and concomitant isomerization of steroidal Δ5-3β-alcohols to the corresponding Δ4-3-ketones in high yield.
SELECTIVITE DE LA REDUCTION D'α-ENONES POLYCYCLIQUES PAR LES BOROHYDRURES: EFFET DE L'ADDITION DE TETRAMETHYL-ETHYLENEDIAMINE AU BOROHYDRURE DE TETRABUTYLAMMONIUM
D'incan, E.,Loupy, A.,Maia, A.,Seyden-Penne, J.,Viout, P.
, p. 2923 - 2927 (2007/10/02)
Δ1,9octalone, Δ1,9-10-methyl octalone and testosterone were reduced by NBu4BH4, alone or in the presence of tetramethylethylenediamine (TMEDA), in THF and in toluene.With TMEDA, the first step of the reduction is the regioselective 1,4 attack by BH4(1-) which leads either to the saturated ketones or to the corresponding saturated alcohols.The results observed under different conditions were interpreted by the intervention of various reductive species: diborane, enoxyborohydrides in the absence of TMEDA, amine-borane in its presence.
Formation of vinyl halides from vinyl cations generated by acetylenic participation in biomimetic polyene cyclizations
Johnson, William S.,Ward, Carl E.,Boots, Sharon G.,Gravestock, Michael B.,Markezich, Ronald L.,McCarry, Brian E.,Okorie, Dominic A.,Parry, Ronald J.
, p. 88 - 98 (2007/10/02)
The object of this study was to examine the fate of vinyl cations of type 4 (resulting from biomimetic polyene cyclizations) in the presence of various halides as sources of nucleophiles. Treatment of the dienynol 1 with trifluoroacetic acid in methylene chloride for 45 min at -78°C resulted in the isolation of the rearranged bicyclic vinyl chloride 6 in 56% yield. Confirmation of the structure and isomeric purity of 6 was obtained by exhaustive ozonization to give diketo ester 9 followed by Wolff-Kischner reduction and then esterification to yield ester 10, the structure of which was confirmed by hydrogen-deuterium exchange of the protons α to the carbomethoxy group. The configuration of the ring fusion in 6 was shown to be trans in the following manner. Selective ozonization gave chloro ketone 11, which was converted into chloro olefin 12 by Wolff-Kischner reduction. Further ozonization afforded keto ester 13, which was converted into diacid 15 by sodium hypobromite oxidation. Esterification afforded diester 16, which was identical with the material obtained via Wolff-Kischner reduction of the known keto diester 17. More careful examination of the products from the aforementioned cyclization also showed the presence of 8% ketone 8 (after hydrolytic workup). Identical cyclization conditions of 1, except at 0°C, gave 55% vinyl chloride 6 and 45% ketone 8 while use of a 7.5:1 pentane-1,2-dichloroethane mixture at 0°C led to 11% vinyl chloride 6 and 89% ketone 8. Cyclization of dienynol 1 with stannic chloride in 1,1-dichloroethylene at -35°C for 45 min gave a 53% yield of three isomeric vinyl chlorides, 7b, 7a, and 6, in a ratio of 8:75:12. The successful cyclization of dienynol 1 led to more extensive cyclization studies of substrates such as 2, 3, and 35, which provided tetracyclic products. The most thoroughly studied case was that of trienynol 3, which, on treatment with stannic chloride in 1,1-dichloroethylene at ca. -30°C for 50 min, gave a 64% yield of three tetracyclic products A, B, and C in a ratio of 15:73:12 by VPC. Product A was shown to be chloro diene 22 by hydrogenation of the Δ1-olefinic bond followed by ozonization to give 5β,13α-androstan-17-one (29), which was compared with an authentic sample prepared by irradiation of 5β-androstan-17-one (25). Products B and C were shown to be chloro dienes 18 and 20 by conversion of the mixture into 5β-androstan-17-one (25) and keto ester 27. A systematic variation of reaction conditions as well as the use of mixed-halide sources led to evidence for a possible mechanism for the formation of all three products from an intermediary tricyclic cation 43.
