Total synthesis of derivatives of (±)-6-oxa and aza-estrone

Designing Total Syntheses

“…It is obvious that in many of these sequences, use of the appropriate heterocyclic compound at one of the stages in the synthesis would give rise to a heterosteroid. For example, the AB + D -> ABD -» ABCD synthesis has been used to prepare 15 (Scheme 1-2), where X = 0 [47], S [48], NH [49], and SiMe 2 [50].…”

Ab + D → Abd → Abcd

“…N-Arylsulfonyl pentaene intermediates with tosyl 67 [83,84] or benzenesulfonyl [85,86] substituents were synthesized in the usual fashion from the requisite ally lie alcohols (e.g., 66). Catalytic hydrogénation of the benzenesulfonyl analog gave the CD-trans tetraene as expected [86], but with 67 a mixture predominating in the 14/?-isomer 69 resulted regardless of whether palladium-on-calcium carbonate, -strontium carbonate, or -charcoal was used as the catalyst [87]. When the hydrogénation was carried out on the 17/?-hydroxy analog 68, prepared from 67 by sodium borohydride reduction, the predominant product was the α-isomer.…”

“…In the benzenesulfonyl series, however, lithium-ammonia reduction of 77 (from 76 and sodium borohydride) gave 74 [86]. An alternative route in carbocyclic steroids is comprised of isomerization of the 8,9-double bond to the 9(ll)-position, followed by catalytic hydrogénation, but 77 would not isomerize under a wide variety of acidic conditions.…”

“…6-Oxasteroids were readily synthesized beginning with the allyl alcohol 101, which was condensed with 2-methyl-l,3-cyclopentanedione in the presence of potassium hydrogen carbonate to the ABD intermediate (Scheme 4-13) [86]. Cyclization to 102, hydrogénation, and isomerization proceeded normally to give the Δ 0(11) -steroid 105.…”

“…The analog 109 without the 17«-ethynyl group was prepared by hydrolysis of 108. 8a-Isomers were obtained by exhaustive hydrogénation of 102 and sodium borohydride reduction of the ketone 103 [86]. C-18 homologs have been prepared also, by using 2-ethyl-l,3-cyclopentanedione in the condensation with 101 [96].…”