Py rolysis of 16-Methylene 17-Oxygenated-POketo Steroids. IV. Synthesis of 3-Hydroy 1,3,5(1 O)-estratrieno[l7,16-~]-2/-nleth?-lfurnn
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Several g r o u p ot \vorkersl l i a x (’ reported tliat cl*troer serum or plasma cliole.tero1 i n I i u i n x i i ~ . Thc clinical use of estrogens for lowering serum cholc.terol in the human male is limited, h o w v e r , because oi thc undesirable horniorixl s i d ~effects of tli l’or wme j ear?, [ittemptq havc been made to synthesizc coinpounds related to the steroidal estrogen., in wliirli tht. I i j pocholezterolemic activitj is dissociated frnm t l i c utitleqiruble estrogenic activit v It ]in* bceri reported that certiiiii claw>\ ot 1icatei.oc) clic steroids, i n ~ ~ h i ctlhie Iietcmcj clic ring is fused to the C”16 aiid C‘li pusitions 111 the Yteroid slxdetoii, exhibit increased h j P(~choIestero1t:mic activitj relative to their ectrogeiiicitj . Tliu-. [lT,l(i-c]pjrazoles.2 [ 17,16-d]-2’-methjltriazoles, :iiitl /2’,3’-16,17]pyr:izinc~s4are described as pow-iiig iiicwwictl 11) pocholc-t erolemic activitie.. The purpose of tlii- articlc I- to describe tlirl p i epar:itioii and Iiypochole~terolealicactivitj of the 1,3,3(10)est rat rieno- [ 17,lti-r.]-2’-methj Ifurun \,I ztcrn. Hecently \ve reported tlie pyrolj tic cmiversinii of Itimetli\ lenc.-l’ia-acetoxy-~O-~(~t~) steroids into th(. corrci~pnnding :~~idrostario [17,1~i-c]-2’-1nrthylfura11s111 ort1t.r to prepare 5 :i simplcl rcpreirntatirc ot thi. stcwidal Iieterocj clic sj btcm. ;I suitablc method for tlic. prcyarwtion of the precursor I 6-methj leriel7a-:ieeto.r1 compound 4 had to be devi-ed. h c t j latioil of lfj-nietli!,leiic.-1ia-~i~~tox! -1 9-11) tlroxj progesterone (l)fi with -Ic#J in pyridine gxvo 2 \iIiicli oii treatment with “,3-dicliloro-j,B-dicj aiiobenzoquinone (DDQ7 :ifforded tlw dierioiie 3. Short expozore of 3 to ethaiiolic IiOH gave the desired 4. So lij drolJ,si.: of tlic 17-acet oxj group uiitler the+ coiic-litioils u a s observed. The over:tll yield of 4 from 1 w:is ahout 5.jc: . T ) ~ ~ I i ~ d r o ~ e n x of t i o1 l i with 8r02 iii IYg ~ i i . IOU
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