45. A stereoselective total synthesis of œstrone, and related studies

Designing Total Syntheses

“…The degree of stereospecificity (absent in the methylation of 62) varies from compound to compound, and depends primarily on the stereochemistry of the material being methylated. Some of these influences are seen in the results of methylation of the isomeric 17a-ketones 69-72 (Scheme 1-7) [71][72][73]. These compounds were first condensed with aromatic aldehyde in order to protect the more reactive 17-position.…”

“…The rationalization of methylation results is not always so straightforward, however; in addition to accessibility, relative stabilities of the transition states also play a role, and these can be severely altered by double bonds at different positions relative to the reaction center [73,74]. The problem of obtaining only the desired geometry in the creation of a new asymmetric center was solved in an ingenious fashion in Wettstein's synthesis of aldosterone.…”

Ab → Abc → Abcd

“…Condensation of naphthalene (58) with /?-methyltricarballylic acid anhydride (59) afforded 60, which was subsequently converted into tetracyclic ester 61 and its 17o:-isomer. Later this method was extensively modified by Harnik [44][45][46][47], who achieved the synthesis of 3,6-dimethoxy-17/^acetyl-l,3,5(10),6,8-estrapentaene (74) and also the corresponding 17/?-acetamido derivative 75 (Scheme 3-7).…”

“…It took six more years before the first synthesis of natural estrone was achieved by Anner and Miescher [50] in 1948. Since then several syntheses [51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67] of estrone have been described in literature. By 1958, Johnson had completed the synthesis of all but one of the eight stereoisomers of estrone [54][55][56][57][58][59].…”

Steroidal Estrogens

“…The shortcomings of the intermolecular Diels-Alder approaches (COLE et al 1962) were elegantly overcome by the intramolecular versions of [4+2] cycloaddition, using appropriately substituted o-quinodimethane precursors (FUNK and VOLLHARDT 1980). Though hitherto un exploited for technical scale manufacture, the various approaches are intriguing examples of modern synthetic methodology applied to steroid framework synthesis (OPPOLZER 1980;KAMETANI 1978;QUINKERT et al 1981).…”