Mihailo Lj. Mihailović

13,14-seco-steroids: A new type of modified steroids containing a nine-membered ring

Oxidations of 14 alpha-hydroxy-5 alpha-cholestan-3 beta-yl acetate (5) with lead tetraacetate under thermal or photolytic conditions or in the presence of iodine proceed mainly by fragmentation of the C(13)-C(14) bond to give as the primary products the 13,18-didehydro-13,14-seco derivative 6 and the (E)-Delta(12)-13,14-seco ketone 11, respectively. Further transformations of these compounds under conditions of their formation afforded, in addition, the acetoxy derivatives 7-9 (from 6), and the D-homo-C-nor compound 12 and (12R,13R)-epoxide 13 (from 11). Unexpectedly, the photolytic lead-tetraacetate oxidation of 5 resulted partly (to ca. 20%) in a reversible fragmentation involving scission and recombination of the C(8)-C(14) bond followed by formation of rite 14 beta,22-ether 10. Possible mechanisms for the observed transformations are discussed.

Oxidative β -fragmentation of 19-nor-5α-androstane-3β, 5, 17β-triol 3, 17-diacetate

Abstract The preparation of 19-nor-5α-androstane 3β,5, 17β-triol 3,17 diacetate (10) is described. When this alcohol was treated with the mercuric oxide-iodine reagent it underwent fragmentation of the C(5)–C(10) bond with formation of a new type of 10-membered ring containing 5,10-seco-steroidal compounds, i.e. (Z)-and (E)-19-nor- 3β, 17β diacetoxy-5,10-seco-androst-1(10)-en-5-one (11 and 12), in 27 and 49% yield, respectively.

Structure-reactivity relationship in 19-methyl-and 19-nor-5,10-secosteroids. Part 4. Intramolecular nitrone 1,3-dipolar cycloadditions

The (Z)-19-nor-5,10-secosteroidal ketone 11 reacts with hydroxylamine hydrochloride to give the (E)- and (Z)-oximes 12 and 13, while with N-methylhydroxylamine hydrochloride it undergoes transannular nitrone 1,3-dipolar cycloaddition to give isoxazolidines 14 and 15, and an estratriene derivative 16, originating from 14. The (E)-19-nor-5,10-seco-ketone 17 undergoes intramolecular nitrone 1,3-dipolar cycloaddition with both hydroxylamine hydrochloride and N-methylhydroxylamine hydrochloride to produce, with the former reagent, a single isoxazolidine 18, and with the latter, two regioisomers 22 and 23. The reaction and stereochemical courses of the above transformations are compared with those previously observed for the corresponding 19-methyl analogues. Copyright (C) 1996 Published by Elsevier Science Ltd.

Structure–reactivity relationships in normal and 19-nor-5,10-seco-steroidal cyclodecenone systems. Part 1. Acid-catalyzed and thermal reactions

Under acid-catalyzed conditions both the (Z)- and (E)-19-nor-seco ketones (1a) and (2a) underwent transannular cyclization [forming the C(5)–C(10) bond], accompanied by aromatization of the resulting ring A, to give estra-1,3,5(10)-trien-17β-yl acetate (4)(in 76% and 83% yield, respectively). On the other hand, when the corresponding 19-methyl analogues (1b) and (2b) were treated with acid under similar experimental conditions, the (Z)-diastereoisomer (1b) remained mostly unchanged, while the (E)-19-methyl-seco ketone (2b) afforded the A-nor-B-homo derivative (5)(in 68% yield). The same transannular cyclization of the (E)-seco ketone (2b) was also achieved thermally in the absence of protonation.

Oxidations with Lead Tetraacetate

Lead tetraacetate (LTA), Pb(OAc)4, is one of the most versatile oxidants in organic chemistry. Depending on the reaction conditions and nature of the substrate, it can be used for selective and partial oxidations of various reactive groupings, but also—and this is of primary importance—for the functionalization of nonactivated carbon atoms. The versatility of LTA originates from its properties: it can act as a radical and/or ionic oxidant and participate in processes involving substitution, elimination, addition, or fragmentation reactions, depending on the functionality and experimental conditions.

Oxidative hydrolysis and acid-catalyzed rearrangement of steroidal isoxazolidines

Abstract Treatment of steroidal isoxazolidines 3a, 3b and 5b with N-methylhydroxylamine hydrochloride in boiling ethanol-pyridine (1:1) solution results in elimination of the CH 3 NH 2 fragment, affording products of oxidative hydrolysis 4a, 4b, and 6b, while acid-catalyzed reaction of isoxazolidines 2a, 3a and 5b leads to rearrangement involving the N-CH 3 group with formation of the perhydro-3,1-oxazine derivatives 8a, 9a and 10b .

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).

Acid-catalyzed rearrangement of some steroidal isoxazolidines

Abstract Acid-catalyzed reaction of the steroidal Δ1-unsaturated 3β,5β-epoxyimino compound 2 and Δ3-unsaturated 1β,5β-epoxyimino products 3 and 7, results in intramolecular rearrangement involving the N-CH3 group to give the corresponding perhydro-3,1-oxazine derivatives 9–11. Under similar reaction conditions, the saturated analogues 4, 6 and 8 remain unchanged. The difference in reactivity between the unsaturated and saturated compounds is studied and elucidated by the semiempirical molecular orbital MNDO-PM3 method.

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.

Non-faradaic electrocatalysis: Part I. Acceleration of ester hydrolysis in the electrochemical double layer⋆

Abstract Pulsation of potential of a gold electrode in the double-layer region, between the p.z.c. and a several hundred millivolts more positive value, was found to increase the rate of hydrolysis of tertiary butyl acetate. The homogeneous rate constant of hydrolysis at 35°C was found to be 1.4×10−6 s−1 in the absence of the electric field imposed by pulsation, while in the presence of the field at the ratio of the electrode surface area to the volume of reacting solution of 0.08 cm−1, it was found to be up to 7.2×10−5 s−1 indicating a heterogeneous rate constant of 9×10−4 s−1 cm−2. Effects of changing the potential limits, the frequency of pulsation and the ratio of time intervals during which the electrode has been maintained at one or the other potential limit have been recorded. The same effects are found when gold was replaced by silver. Tertiary butyl acetate is known to undergo hydrolysis by bond breaking between oxygen and tertiary carbon atom and the formation of a carb-cation radical intermediate. It is assumed that the catalytic effect is due to the polarisation of the adsorbed and suitably oriented molecules along the bond in the high electric field acting upon it in the Helmholtz layer during the potential pulse. The process is a non-faradaic one since no charge is transferred across the double layer.