Study On Synthesis Of Finateride

As a 4-a za-s teroidal compound, Fin aste rid e is a kind of 5α-reducin genzyme inhib itor, which can sele ctively and comp etitively in hibit theactivity of 5α-reducing enzyme . It pla ys an imp orta nt functio n in ma nyandrogen-s ens itive tis s ues. Finas teride is be coming the firs t choice for th etre atment of Benign Pros tatic Hyp eplas ia by virtue of th e definite curativeeffe ct and lo w to xicity.In th e lite rature, Fin aste rid e A ring was re builded from 3-ox o-4 -androste ne compound by cle avage ofΔ~4 -double bo nd by oxidation, ringclosu re by amin ation, hydrolyzation ofΔ~5 -doub le bond. Howeve r, prec iousme tals (Pd, Pt) are used for hyd roly zation ofΔ~5 -dou ble bond, which isunnece ss arily in trod uced when ring closure by amination. In orde r toovercome th ese disad vantage s, it is ne ces sa ry to prop ose a new meth od forA ring re building.In th is paper, pregne nolone is converted to meth yl 3-ox o-4 -a ndroste ne-17β-c arboxylate through King rea ction, Oppe naue r oxidation. Three route sare desig ned for A ring rebuild ing from me thyl 3-oxo -4-an dro stene -17β-carboxyla te. Route 1: me thyl 3-oxo-4-and ros tene -1 7β-ca rb oxylate is con -verted to me thyl A-norand ros tane -3 -oxo -16 -c arboxylate through epoxid -ation and epoxide cons tric ted re arra ngemen t. Route 2: me thyl 3-oxo -4-androste ne-17β- carboxyla te is converted to me thyl A-n ora ndrosta ne-3-oxo-16-c arboxyla te through Baeye r-Villig er oxidation and unsa tura ted la ctonecons truc ted ring rea rran gement. Route 3: meth yl 3-oxo-4-andros tene -17β-carboxyla te is converted to me thyl 5-c arboxyl-3-oxo-4-oxa -an dros tane t-17β-c arboxylate through oxidation by m-C PBA, re arra ngemen t by sodiumhydroxide solution, oxidation by sodium chlorite. The effe cts of differenc ere action conditions on th e yield of prod uct in ea ch step have be enin ves tigated and opimal re action condition ha s been found. Eac h prod uctwas id entified by NMR or/an d MS.