ABSTRACT
A number of 5,10-seco analogs of testosterone has been synthesized starting from products of the radical oxidation of 3beta,17beta-diacetoxy-5alpha-androstan-5alpha-ol. The obtained compounds possess a flexible 10-membered ring with substituents (O, -OH) at C-3 and C-5. Similar derivatives with an (E)- and (Z)-Delta(1(10))-double bond have been prepared also. X-ray analysis and a combination of NMR experiments have been used for their structure elucidation and conformation analysis.
Subject(s)
Secosteroids/chemical synthesis , Testosterone/chemical synthesis , Crystallization , Crystallography, X-Ray , Cyclization , Magnetic Resonance Spectroscopy , Molecular Conformation , Testosterone/analogs & derivativesABSTRACT
The synthesis of a 5,10-seco steroid containing two double bonds in a AB-macrocycle as well as the preparation of a steroidal skeleton with a cyclobutane fragment is described. The structures of these compounds are different from those of natural steroids, but they are very similar with respect to conformation of the carbon skeleton.
Subject(s)
Cyclobutanes/chemistry , Steroids/chemistry , Models, Molecular , Molecular Conformation , Molecular Structure , Oxidation-Reduction , Ozone/chemistry , Secosteroids/chemical synthesis , Secosteroids/chemistry , Structure-Activity RelationshipABSTRACT
A new synthesis of both epimeric forms of 26-cholestanoic acids and 26-alcohols containing a 3beta-hydroxy-Delta(5)- or a Delta(4)-3-keto-functionality in ring A is described starting from stigmasterol or (20S)-3beta-acetoxy-pregn-5-en-20-carboxylic acid. The obtained compounds are useful as standards for studies of cholic acids. Construction of the side chain was achieved by linkage of steroidal 23-iodides to sulfones prepared from (2R)- and (2S)-3-hydroxy-2-methylpropanoates. Oxidation of intermediate 26-alcohols into the corresponding carboxylic acids ensuring preservation of stereochemistry at C-25 and functional groups in the cyclic part was achieved with sodium chlorite catalyzed by TEMPO and bleach.
Subject(s)
Cholestanones/chemical synthesis , Cholic Acids/biosynthesis , Alcohols/chemistry , Carbon Isotopes , Carboxylic Acids/chemistry , Catalysis , Cholestanones/chemistry , Chromatography, Thin Layer , Magnetic Resonance Spectroscopy , Molecular Structure , Oxidation-Reduction , Pregnanes/chemistry , Stereoisomerism , Steroids/chemistry , Stigmasterol/chemistry , Sulfones/chemistryABSTRACT
This paper elaborates an improved synthesis of crinosterol and campesterol starting from stigmasterol. The proposed approach is based on Claisen rearrangement of Delta23-22-allylic alcohols with various configurations of the 22-hydroxy group and geometry of the Delta23-double bond. It allows complete use of the starting steroid for preparing 24alpha-methyl derivatives. It was possible to partially control the stereochemistry at C-25. Hydrogenation of the Delta22-double bond was shown to proceed with partial isomerization of the C-24 alkyl substituent. The Ireland ester enolate variant of the Claisen rearrangement was demonstrated to be useful for preparing 24alpha-methyl steroids containing the Delta22,25-system.
