YU46712B

YU46712B - PROCEDURE FOR OBTAINING NEW MICROLIDE COMPOUNDS

Info

Publication number: YU46712B
Application number: YU148788A
Authority: YU
Inventors: D.R. Sutherland; O.Z. Pereira; H.M. Noble; M.V.J. Romsay; J.B. Ward; R.A. Fletton; E.P. Tiley; N. Porter; D. Noble
Original assignee: American Cyanamid Co.
Priority date: 1987-04-08
Filing date: 1988-08-02
Publication date: 1994-04-05
Also published as: YU148988A; YU46714B; YU148788A; YU148888A; YU106689A; HRP920589B1; HRP920589A2; YU46713B; YU218687A; YU46777B; YU47126B; GB8708423D0; SI8712186A

Abstract

POSTUPAK ZA DOBIJANJE NOVIH MIKROLIDNIH JEDINJENJA, opšte formule (I): i njihovih soli, pri čemu u formuli: R1 pretstavlja metil, etil ili izopropil grupu: R2 pretstavlja vodonikov atom, C1-4alkil grupu ili alil grupu i grupa =NOR2 je u E-konfiguraciju; i OR3 je hidroksilna grupa ili -OR4' -OCOR4 ili -OCOOR4, gde je R4 C1-4alkil ili -OCOR8 R9, gde su R8 i R9 nezavisno vodonik ili C1-4alkil, naznačen time, što za dobivanje jedinjenja formule (I) u kojoj je OR3 hidroksilna grupa, obuhvata redukciju jedinjenja formule (III) u kojoj R1 i R2 imaju gornjua značenja, sa redukcionim sredstvom izabranim iz grupe koja sadrži borohidride alkalnih metala i alkoksialuminijum-hidrida littijuma, poželjno sa natrijum-borohidridom, u nekom alkalnom rastvaraču, kao što je izopropilalkoholu ili izobutilalkoholu, na temperaturi u intervalu od -30 do + 80В° C, najpodesnije na 0 ; posle čega se, prema potrebi, vrši konverzija OR3 grupe u supstituisani hidroksilnu grupu reakcijom dobivenog jedinjenja sa reagensom izabranim iz grupe koji obuhvata kiselinu formule R4COOH, ili njen reaktivni derivat, kao što je hlorid, anhidrid, ili aktiviran estar, pri čemu se reakcija vrši na konvencionalan način u prisustvu sredstva za vezivanje kiseline tercijarnog amina kao što je dietilamin, piridin i slični, ili sredstva za kondenzaciju kao što je karbodimid, N,N'-dicikloheksilkarbodimid, pri čemu se reakcija vrši u ne vodenim sredinama na temperaturi u intervalu -20 do +100 C; i potom, ako se želi, za pravljenje jedinjenja formule (I) u kojoj je R2 C1-4alkil ili C3alil grupa, jedinjenje formule (I) u kojoj je R2 atom vodonika i OR3 supstituisana hidroksilna grupa, reaguje sa sredstvom za eterifikaciju formule R2Y, gde je R2 kao što je definisano ranije a Y je odlazeća grupa, pri čemu se ova reakcija vrši na uobičajeni način, i konačno, ako se želi, uklanja se zaštita sa OR3 zaštićene hidroksilne grupe, i ako se želi, prevodi se jedinjenje formule (I), u svoje soli.A process for the preparation of novel MICROLIDE COMPOUNDS of the general formula (I) and their salts, wherein in the formula: R1 represents a methyl, ethyl or isopropyl group: R2 represents a hydrogen atom, a C1-4alkyl group or an allyl group and the group = NOR2 is in E -configuration; and OR3 is a hydroxyl group or -OR4 '-OCOR4 or -OCOOR4, wherein R4 is C1-4alkyl or -OCOR8 R9, wherein R8 and R9 are independently hydrogen or C1-4alkyl, wherein to obtain the compound of formula (I) in wherein OR3 is a hydroxyl group, comprising reducing a compound of formula (III) in which R 1 and R 2 have the above meanings, with a reducing agent selected from the group consisting of alkali metal borohydrides and lithium alkoxyaluminum hydride, preferably sodium borohydride, in an alkaline solution such as isopropyl alcohol or isobutyl alcohol, at a temperature in the range of -30 to + 80V ° C, most preferably at 0; then, if necessary, converting the OR3 group to a substituted hydroxyl group by reacting the resulting compound with a reagent selected from the group consisting of an acid of formula R4COOH, or a reactive derivative thereof, such as chloride, anhydride, or activated ester, wherein the reaction is performed in a conventional manner in the presence of a tertiary amine acid scavenger such as diethylamine, pyridine and the like, or a condensing agent such as carbodimide, N, N'-dicyclohexylcarbodimide, the reaction being carried out in non-aqueous media at a temperature in the range - 20 to +100 C; and then, if desired, to form a compound of formula (I) wherein R 2 is a C 1-4 alkyl or C 3 alyl group, a compound of formula (I) wherein R 2 is a hydrogen atom and OR 3 is a substituted hydroxyl group, is reacted with an esterifying agent of formula R 2Y, wherein R 2 is as defined previously and Y is a leaving group, this reaction being carried out in a conventional manner, and finally, if desired, deprotected from the OR 3 protected hydroxyl group, and if desired, a compound of formula ( I), in its salts.