Krducticiii of thc acctoxyniethylene ketone
16 yicldcd a rnixturz of two cpinicric diols 3a and 4a. which wcrc convertcd into thc p-iolucnrsulfonatcs 36 aiid 46. Solvolysis o13d in dry acctic acid Steroide, XXXVII I? -Nacbbargruppen-Beteili~ng. V l l I ". -Nachbargruppen-Beteiligung bei 1Cliydroxgmethyl-3-methoxy-~t~-1,3~lO)-trien-17-olSteroiden ;tTfdcJ 5b :ificr invcrsion at C-17. As an explanation for the forniaticm of 5b. it was assumcd that Ihe cyclic cation 8 may be ;in inicmicdiate. This was confirmed by methanolysis or 3d leading IQ thc orrhocsicr 10. Thu ncighbouring group participation I hc0-6) obscrved during solvolysis of 3d w a s coinplctcly absent iii ilic cast oC 4d. solvolysis of which yicldcd t 7P-acetoxy-16%-;IcctuuS:nicihvI-?-mct liox ycstra-t .3.y 1 O)-tricne (4 b) with mention in horii acrtic acid aiid mcthanol.
Hydrophilic functional groups attached to ring D in the sterane skeleton have a strong effect on the biological properties of these compounds; they also provide a possibility for the construction of heterocycles condensed to the sterane skeleton. The introduction of hydrophilic groups to ring D has already been performed for compounds with the androstane ~k e l e t o n ~-~) .
In this paper we describe modifications of ring D in the estrane series.
Treatment of 3-methoxyestra-l,3,5(10)-trien-17-one, with NaOMe and freshly distilled ethyl formate by a slight modification of a literature method", gave l a in a yield of 87%.
Its acetyl derivative 1 b, obtained quantitatively by reaction of l a with acetic anhydride in pyridine, was reduced with NaBH4 in ethanol to give 3a and 4a in 93% yield. In the first step, the reduction led to 16-acetoxymethylene-3-methoxyestra-1,3,5(10)-trien-l7~-ol(2a). However, in the slightly alkaline medium the acetoxymethylene group was deacetylated and further reduction resulted in a mixture of 3a and 4a. In this two-step reduction of the dicarbonyl system, the otherwise frequently occurring side reaction 7, could be avoided.
In the reaction two new chirality centres are formed, and thus in theory four isomers (3a,4a,5a,6) could be obtained. However, only the isomers 3a and 4 a were isolated, in almost equal amounts. 3a and 4a could easily be separated Reduktion des Acetoxymethylen-Ketons I b licfcrt eiii Gcmiscli zwcier cpimcrcr Diolc 3a und 4a, dic in dic p-Toluolsiilfonatr 3d und 4d ubcrgcfiihrt wcrdcn. Solvotyse von 3d in lrnckcner tissipsiurc crgibt ncbcn 3 b untcr particller Invcrsion an C-17 5b. L ~H S als Zwischcnstufe postuliertc cyclischc Kation 8 kann durch Mcthanolysc als Orrhocstcr 10 abgcfangcn wcrdcn. Die hi Solwlyac von 3d beobachtetc Nachbdrgruppcn-Retcilieung ( AcO-6) i r i i t in1 Falle dcs Toluolsulfonatcs 46 nicht ein. da dessen S o l v d y c sowohl in Essigslure a k auch in Methanol untcr Rctcnlion J e r KonIiguration an C-I7 zu l7fLAwtoxy-1 ba-acetcinymetliyl-3- mcthoxycstra-I,3,5(fO)-trien (4bl fiihrt.