Milan Dabović

Thionation of Some α,β-Unsaturated Steroidal Ketones

The reactions of selected α,β-unsaturated steroidal ketones with Lawesson’s reagent (LR) in CH2Cl2 and toluene under the standard reaction conditions and with a combination of phosphorus pentasulfide with hexamethyldisiloxane (P4S10/HMDO) in 1,2-dichlorobenzene (ODCB) under microwave irradiation were investigated and for this purpose several cholestane, androstane and pregnane carbonyl derivatives were chosen. Depending on the reagent and the solvent, 19 new sulfur containing compounds, including dithiones 4c and 4d, α,β-unsaturated 3-thiones 3a-e, dimer-sulfides 2a-e, 1,2,4-trithiolanes 5a-e and phosphonotrithioates 6b-e were synthesized. All newly prepared compounds were characterized by IR, 1H- and 13C-NMR spectroscopy and elemental analysis.

Free-radical oxidative transformations of androst-4-ene-3β-9α-17β-triol 3,17-diacetate

The oxidation of androst-4-ene-3β,9α,17β-triol 3,17-diacetate (2) with lead tetraacetate resulted mainly In β-fragmentation of the C(9)–C(10) bond to give a mixture of 10α- and 10β-acetoxy-Δ4-unsaturated 9,10-seco-steroidal ketones (3a and 3b) as the minor components (in ~7% yield) and the rearranged 4β-acetoxy-Δ5(10) -unsaturated 9,10-seco-9-ketone (4) as the major product (in 61% yield). Unexpectedly, when the same substrate (2) was subjected to the mercuric oxide - iodine oxidation, it underwent predominantly α-epoxidation of the olefinic double bond to produce the 4α,5α-epoxy derivative (5) (in 58% yield).

Non-sensitized photooxygenation of some steroidal isoxazolidines

Abstract UV irradiation of the steroidal isoxazolidines 2a , 2b , and 2c in various solvents in the presence of molecular oxygen, results in oxidative cleavage of the epoxyimino bridge to give several products; the N-unsubstituted isoxazolidine 2a afforded the nitro products 3 , 4 , and 5 and the azoxy compounds 6 and 7 , while the N-methyl and N-acetyl derivatives 2b and 2c produced only the nitro compounds 3 and 5 as sole identifiable material. An explanation of the observed photooxygenation processes involving exciplex formation followed by proton transfer from isaxazolidine to molecular oxygen is presented.

Photochemically induced mercuric oxide - iodine oxidation of some unsaturated steroid compounds

Abstract Photochemically induced HgO/I 2 oxidation of cholest-5-en-3α-ol (6) and cholest-5-en-3β-ol (7) afforded (Scheme 3) products arising from the corresponding alkoxy radicals ( 12, 13 and 14a,b ) and from attack of the I 2 O intermediate at the olefinic double bond (epoxides 15a and 16a,b respectively). With cholest-5-ene-1α,3β-diol 3-acetate ( 8 ) and cholest-7-ene-3β,5α-diol 3-acetate ( 9 ) the HgO/I 2 oxidation led to unresolvable complex mixtures (Scheme 5). With the same reagent cholest-5-en-3α-ol acetate ( 10 ) and cholest-5-en-3β-ol acetate ( 11 ) underwent exclusively attack by I 2 O, to give epoxides 20a,b , iodohydrin 21 , and rearranged products 19 and 22 (Scheme 7), in the case of 10 , and predominantly epoxides 23a,b (Scheme 8), in the case of 11 .

Synthesis, structure, and reactions of secosteroids containing a medium-sized ring. Part 17. Structure–reactivity relationship in the solvolysis of 5,10-secosteroidal 3-tosylates

Kinetic measurements of the solvolysis of (Z)-3α- and (Z)-3β-, and (E)-3α- and (E)-3β-tosyloxy-5,10-secocholest-1(10)-en-5-ones in buffered aqueous acetone (90 : 10 v/v) reveal that the (Z)-3α-, (E)-3α-, and (E)-3β- tosylates are solvolysed according to a first-order rate law (the relative rates being ca. 1 : 3 : 8), while the (Z)-3β-ester, under the same conditions, reacts at a much slower rate by a complex mechanism, the kinetics of which are best approximated by a second-order law. These data and product analysis indicate that the former three esters are solvolysed with considerable double bond participation [resulting in the case of the (E)-3-esters in intramolecular cyclopropane ring closure], and that this interaction is unimportant for the (Z)-3β-tosylate. On the basis of conformational analysis of the starting tosylates and stereoelectronic requirements for homoallylic interaction, a possible mechanistic pathway for these solvolyses is proposed.

Structure-reactivity relationship in the solvolysis of 5,10-secosteroidal 5-p-nitrobenzoates

Abstract The solvolysis of ( Z )- and ( E )-3β-acyloxy-5,10-seco-1(10)-cholesten-5β-ol p -nitrobenzoates 4 and 5 has been investigated and compared with the solvolytic reactivity of the epimeric ( Z )- and ( E )-5α- p -nitrobenzoates 1 and 2 , as well as of the reference compound, i.e. the 1,10-saturated 5α- p -nitrobenzoate. Kinetic data and product analysis revealed that the relative spatial orientation of the 1(10)-olefinic double bond and the chiral center at C(5) in the 10-membered ring, which these secosteroidal 5- p -nitrobenzoates can adopt in the transition state, is the main factor which determines their solvolytic behaviour, so that the esters 1 , 2 and 5 solvolyse with transannular double bond participation, while such an interaction is not present in the case of the ( Z )-5β-ester 4 .

Homoallylic interaction in steroidal cyclodecenyl systems

Solvolysereaktionen an den steroidartigen Cyclodecenyl-Verbindungen (I) bzw. (II) werden in ihrer Kinetik sowie hinsichtlich der gebildeten Reaktionsprodukte diskutiert.

Cyclisation of alkoxy radicals. A semiempirical MNDO-PM3 study

The reactivity of the butoxy and 3-methylcyclohexyl radicals, as representatives of alkoxy radicals, was studied by MNDO-PM3 semiempirical MO method. In both cases it was found that the oxy radical underwent easily 1,5-H migration giving a δ-hydroxyalkyl radical. The hydrogen abstraction reaction goes through two transition states. The first transition state (TS) with short O–H distance has an energy very similar to, or lower than, the TS for 1,5-H migration. The second TS is of higher energy and is much product-like. The overall cyclisation reaction has a high activation energy (over 40 kcal mol –1), and is therefore unlikely to occur spontaneously. Most likely, the cyclisation step needs assistance of some other surrounding molecules to speed up the reaction.

Mercuric Oxide — Iodine Oxidation of Steroidal Homoallylic Alcohols

Our previous study has shown that the oxidation of androst-4-ene-3β,9α,17β-triol 3,17-diacetate (1) with mercuric oxide — iodine results predominantly in α-epoxidation of the olefinic double bond to produce, as the only detectable reaction product, the 4α,5α-epoxy derivative (2) (in about 60% yield) (Scheme).

Stereochemically Controlled Acetalizations in the Ten‐Membered Ring of (Z)‐ and (E)‐5,10‐Seco‐Steroidal Ketones.

The (Z)-cholestenone (I) reacts wi-th MCPBA to give the cis-epoxide (II) which undergoes stereospecific intramolecular cyclization to afford the acetal (VIa).