Mass spectrometric analysis of androstan-17β-ol-3-one and androstadiene-17β-ol-3-one isomers

Mass spectrometric identification and characterization of steroids using electrospray ionization and tandem mass spectrometry has advantages in drug testing and doping control analysis attributable to limitations of gas chromatography followed by electron ionization mass spectrometry. Steroids with an androstadiene-17beta-ol-3-one nucleus and double bonds located either at C-1 and C-4, C-4 and C-9, or C-4 and C-6 were used to determine characteristic fragmentation pathways. Diagnostic dissociation routes are proposed using deuterium labeling, MS3 experiments, and analyses of structurally closely related compounds. Steroids such as boldenone (androst-1,4-diene-17beta-ol-3-one) produced characteristic product ions at m/z 121, 135, and 147. Compounds with double bonds at C-4 and C-9 generated abundant product ions at m/z 145 and 147. Conjugated double bonds at C-4 and C-6 gave rise to an intense and characteristic signal at m/z 133. Stereochemical differentiation between 5alpha- and 5beta-isomers of androstan-17beta-ol-3-ones was possible because of significant differences in relative abundance of product ions generated by elimination of acetone from alpha,beta-saturated 3-keto steroids.     

Simple Synthesis of 17α,20β-Dihydroxypregn-4-en-3-one

Reduction of 17-hydroxyprogesterone (1) with NaBH ₄ produces 17,20-dihydroxypregn-4-en-3-one (2) and pregn-4-en-3,17,20-triol (3)     

Facile Synthesis of 6β-Hydroxy-7α(H)-eudesma-4-en-3-one and β-Cyperone

Eudesmane derivatives have been drawing considerable attention due to their wide spectrum of biological proerties, particulaly antifeedant, cell growth inhibitory and plant growth regulating activities.¹ In recent years a number of C-6 oxyfunctionalized eudesmanes and β-dihydroagarofurans,such as compounds 3-6,have been isolated from nature sources. However the reports on the synthesis of this particular kind of compounds are few and the reported syntheses are generally by synthetic methodology starting from α-santonin 2². Our interest of study on the synthesis of this kind of compounds prompted us to investigate a new synthetic route from cheap material (+)-dihydrocarvone 7.     

A Facile Synthesis of 4-(3β -Methoxy-5α-androstan-17β-YL)-3-pyrrolin-2-one

The title compound was prepared in 4 steps from 3β-methoxy-21-hydroxy-5α-pregnan-20-one (1). The required intermediate (4) was obtained using lithium enolate derived from t-butyl acetate. Interesting enough, p-tosyl chloride in pyridine quantitatively converted compound 1 into the α-chloro ketone derivative (2).     

A Facile Synthesis of 6β-Hydroxy-7α(H)-eudesma-4-en-3-one

Sesquiterpenesconstituteagroupofnaturalcompoundswhichexhibitconsiderablebiologicalactivities,suchasantiinflamatoryicytyotoxic'andcytotoxic',seedgendnation'andmolluscacidalactivities4.InrecentyearsanumberofC-6oxyfunctionalizedeudesmanesand6-dihydroagarofurans,suchascomPounds3-6',havebeenisolatedfromnaturesources.HoweverthereportSonthesynthesisofthisparticularkindofcompoundsarefewandthereportedsynthesesaregenerallybysyntheticmethodologystartingfroma-santonin2e.Ourinterestofstudyonthesynthesisof…     

Synthesis of (24R)-3β-hydroxystigmast-5-en-7-one

The natural compound (24R)-3-hydroxystigmast-5-en-7-one has been synthesized from -sitosterol.Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus', 220141, Belarus', Minsk. Ul. Akad. Kuprevicha, 5/2. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 484–487, July–August, 1999.     

First Total Synthesis of 3α,4α-Oxidoagarofuran and (-)-3β,4α-Dihydroxy-β-dihydroagarofuran

The first stereoselective total synthesis of (–)-3β, 4α-dihydroxy-β-dihydroagarofuran (1) and 3α, 4α-oxidoagarofuran (2) has been described. The key step is the epoxidation of α-agarofuran (6) with dimethyldioxirane.     

The structure of 16, 17β-epoxy-17α-pregn-5-en-3β-ol-20-one monohydrate

The structure of the title compound (1) has been studied by means of X-ray diffraction. The region of cycleD in epoxide1 was compared with that of the 16,17-epoxy derivatives of progesterone and pregnenolone (studied previously) as well as with that of the respective 16,17- and 16,17-cyclopropano analogs. In contrast to the 16,17-epoxy-20-oxo derivatives, in compound1 the electron conjugation of the epoxide ring with the CH₃CO group at C(17) is partly disrupted. Moreover, the steric congestion at C(17) is significantly less pronounced in 16,17-epoxide1 than in its 16,17-counterpart. Both of these factors, especially steric decongestion, are favorable for nucleophilic attack at C(17) in the molecule of1. The X-ray diffraction data do not contradict the previously advanced mechanism of epoxide ring opening in 16,17- and 16,17-epoxy-20-oxo steroids by nucleophilic reagents.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 401–405, February, 1993.     

Stereospecific total syntheses of 7α- and 7β-eremophilane-6-one and 7α- and 7β-eremophilane

The title compounds have been prepared in a highly efficient fashion by a synthetic route involving an intramolecular Diels-Alder reaction of an acetylenic thiazole followed by reductive modification of the resulting fused-ring thiophene.     

A Total Synthesis of (±)-α-Chamigrene-3-one

Thephotocycloadditionofmethyl2,4-dioxopentanoate1toalkenesorconjugatedolefins2regioselectivelygavethecycloadduct3(Schemel).ThisreactioncouldconvenientlybeusedtoconstructthebasicframeworkofvariousnatUraIlyoccutringchamigran-tyPespirosesquiterPenes,suchasa-chamigrene",6-chamigrene:=,andaseriesofrelatedhaIogenatedderivativesd.The(i)-Q-Chamigrene-3-onewasanewmemberofthisfamilyandwasrecentlyisolatedfromMarchantiapolymorPha".whichpossessedthestrUctUreofasyntheticintermediate,1-methoxycarbonyl-5,…     

Synthesis of (24R)-3β,5,14α-trihydroxy-5α-stigmast-7-en-6-one 3-benzoate

An ecdysteroid analog has been synthesized from -sitosterol.Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus', 220141, Belarus', Minsk, ul. Akad. Kuprevich, 5/2. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 488–491, July–August, 1999.     

Synthesis of Novel 17α-Eethynyl-5-androstene-3β, 7β, 17β-triol (HE3286)Derivatives

以脱氢表雄酮为原料,经羟基乙酰化,羰基亚乙二氧基化,CrO3/3,5-二甲基吡啶氧化,硼氢化钠还原,脱17-位亚乙二氧基,脱3-位乙酰基,用叔丁基二甲基氯硅烷(TBDMSC1)保护3,7-OH,17-位环氧化,17-位开环,脱TBDMSC1保护等十步反应合成了四个新型的17α-乙炔基-5-雄甾烯-3β,7β,17β-三醇(HE3286)衍生物,其结构经1H NMR和MS表征.     

Synthesis and molecular structure study of 3-methoxy-7α-methyl-6-oxa-9β,14β-estra-1,3,5(10)-trien-17-one in solution

It was established by NMR spectroscopy that the catalytic hydrogenation of 3-methoxy-7α-methyl-6-oxa-14β-estra-1,3,5(10),8-tetraen-17-one leads to the formation of 3-methoxy-7α-methyl-6-oxa-9β,14β-estra-1,3,5(10)-trien-17-one, the structure of which was investigated in solution. The corresponding analog with a free hydroxyl group at the position 3 possesses an antiradical activity at the absence of uterotropic effect.     

Reaction of Pregnenolone and 3α,5-Cyclo-5α-pregnan-6β-ol-20-one with Trifluoroperacetic Acid

The reaction of pregnenolone and 3,5-cyclo-5-pregnan-6-ol-20-one with trifluoroperacetic acid produces the trifluoroacetates, hydrolysis of which gives the 3,5alpha;,6-triol.     

Synthesis of lsochroman-4-one and Its Derivatives (Ⅰ)

The medium was modified in the synthesis of the isochroman-4-one.Twenty-one of isochroman-4-one derivatives were synthesized.Among those there were five o-acyl oximes,six mannich bases,four 3-methylene substituted compounds and six pyrimidino and pyrazolo derivatives of isochroman-4-one.Part of the Mannich bases of isochromanone in animal indication was tested     

Autooxidation of Δ17(20)-20-hydroxy derivatives of steroids. Synthesis of 3β-acetoxy-17α-hydroperoxy-16α-methylpregn-5-en-20-one and its reduction to 17α-hydroxy derivative

An efficient procedure was proposed for the synthesis of 3β-acetoxy-17α-hydroperoxy-16α-methylpregn-5-en-20-one. Optimal conditions were found for the combined process including 1,4-addition of methylmagnesium bromide at the Δ¹⁶-20-oxo fragment of dehydropregnenolone acetate and autooxidation of resulting bromomagnesium 3β-acetoxy-16α-methylpregna-5,17(20)-dien-20-olate. The subsequent reduction of the 17α-hydroperoxy group and hydrolysis of the 3β-acetoxy group afforded 17α-hydroxy-16α-methyl-substituted dehydropregnenolone acetate and its 3-hydroxy analog in high yield.     

Synthesis of 3β,6α-dihydroxy-5α-cholan-23-one

Evidence for the presence of 3β,6α-dihydroxy-5α-chol-9(11)-en-23-one in the aglycone mixture from the starfish Marthasterias glacialis is provided by the synthesis of 3β,6α-dihydroxy-5α-cholan-23-one (19) and its identification in the hydrogenated aglycone mixture. The side-chain is constructed from the 23,24-dinorcholanol (13) by reaction of the 22-tosylate (16) with the acetylide anion, followed by hydration of the resulting 23-yne (17).     

Synthesis of ( )-5α-Hydroxy-β-selinene and (-)-5β-Hydroxy-β-selinene

Eudesmanederivativeshavebeendrawingconsiderableattentionduetotheirwidespectrumofbiologicalproperties,particularlyantifeedant,cellgroWthinhibitoryandplantgroWthregulatingactivitiesl'2.Recently,twoepimericeudesmanederivatives( )-5a-hydroxy-6-selinene1and(-)-56-hydroxy-6-selinene2wereisolated3fromtheaerialpartsofCSubtraPicaFMell.,andtheirstructuresweredeterminedbyspectroscopicmethods.Herein,wereportafacilesynthesisofbothtwodiastereomers1and2from( )-dihydrocarvone3infivesteps,usingtheregioselect…     

Synthesis and Biological Properties of 3-(Dihydroxybenzoyloxy)methyl- and 3-(Diacetoxybenzoyloxy)methyl-7α-chlorocephalosporanate Sulfones

We describe the synthesis of tert-butyl esters of 3-(2-hydroxybenzoyloxy)methyl-, 3-(dihydroxybenzoyloxy)methyl-, and 3-(diacetoxybenzoyloxy)methyl-7-chlorocephalosporanic acid sulfones by reaction of tert-butyl ester of 3-bromomethyl-7-chlorocephalosporanic acid sulfone with salts of hydroxy- and acetoxy-substituted benzoic acids. We have investigated the elastase-inhibiting properties of the compounds obtained and also their in vitro cytotoxic activity.     

Synthesis and reduction of 9-(α-nitrophenacylidene)-4-azafluorene

Reaction of 9-phenacylidene-4-azafluorene with acetyl nitrate produces a mixture of geometric isomers of 9-(-nitrophenacylidene)-4-azafluorene. The nitro group splits off upon reduction of the product in the system zinc-ammonia and zinc-acetic acid and on Raney nickel. Proceeding of the Henry retro-reaction has been pointed out.Russian Peoples' Friendship University, Moscow 117918, RussiaTranslated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 342–347, March, 1999.