Everolimus, RAD-001, NVP-RAD-001, SDZ-RAD, Certican
依维莫司Chemical Name: [1R,9S,12S[1'R(1''S,3''R,4''R)],15R,18R,19R,21R,23S,30S,32S,35R]-1,18-Dihydroxy-12-[2-[4-(2-hydroxyethoxy)-3-methoxycyclohexyl]-1-methylethyl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.0(4,9)]hexatriaconta-16(E),24(E),26(E),28(E)-tetraene-2,3,10,14,20-pentaone; 40-O-(2-Hydroxyethyl)rapamycin; (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-Hexadecahydro-9,27-dihydroxy-3-[2-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl]-1(R)-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentaone
CAS No. 159351-69-6
项目整合开发状态: Launched-2004
项目研究机构: Novartis (Originator), Guidant (Licensee)
合成路线:Alkylation of rapamycin (I) with 2-(tert-butyldimethylsilyloxy)ethyl triflate (II) by means of 2,6-lutidine in hot toluene gives the silylated target compound (III),which is deprotected by means of 1N HCl in methanol.
📌 参考资料/链接：
参考文献标题:O-Alkylated rapamycin derivs.and their use,particularly as immunosuppressants
文献作者:Cottens,S.; Sedrani,R.(Novartis AG; Novartis Deutschland GmbH)
参考来源:EP 0663916; EP 0867438; JP 1996502266; JP 1999240884; US 5665772; WO 9409010
📄 详细内容
合成路线:Alkylation of rapamycin (I) with 2-(tert-butyldimethylsilyloxy)ethyl triflate (II) by means of 2,6-lutidine in hot toluene gives the silylated target compound (III),which is deprotected by means of 1N HCl in methanol.
参考文献标题:SDZ-RAD
文献作者:Castar,J.; Sorbera,L.A.; Leeson,P.A.
参考来源:Drugs Fut 1999,24(1),22
合成路线:The compound has been obtained biosynthetically by an optimized fermentation process using Streptomyces hygroscopicus mutant RSH 1701 with a complex culture medium were [14C]-labeled (1R,3R,4R)-2,3-dichydroxycyclo-hexanecarboxylic acid (I) and [14C]-labeled (S)-pipecolic acid (II) have been added.This fermentation process yielded [14C]-labeled rapamycin (III),which was finally selectively O-alkylated at the C-40 position with monosilylated ethylene glycol triflate in DMSO/dimethoxyethane.
合成路线:The reaction of the labeled acylated (+)-bornane-10,2-sultam (IV) with triethyl phosphite gives the phosphonate (V),which is treated with paraformaldehyde,galvinoxyl and K2CO3 yielding the acrylate derivative (VI).The cyclization of (VI) with butadiene (VII) by means of diethylaluminum chloride and galvinoxyl (as radical scavenger) affords the cyclohexene-carboxamide derivative (VIII),which is hydrolyzed with LiOH in THF/water giving the (1R)-3-cyclohexenecarboxylic acid (IX).The oxidation of (IX) with m-chloroperbenzoic acid and triethylamine in CCl4 yielded regioselectively the hydroxylactone (X),which is finally hydrolyzed with HCl to the labeled intermediate (I).
合成路线:The reaction of the labeled acylated (-)-bornane-10,2-sultam (XI) with benzophenone imine (XII) gives the glycylsultam derivative (XIII),which is alkylated with 4-iodobutyl chloride (XIV) by means of butyllithium and DMPU in THF yielding intermediate (XV).The selective hydrolysis of (XV) with HCl affords the omega-chloro-L-norleucine derivative (XVI),which is cyclized by means of tetrabutylammonium fluoride and DIEA in hot acetonitrile giving the (2S)-piperidyl derivative (XVII).Finally,this compound is hydrolyzed with LiOH in THF/water to the labeled intermediate (II).
参考文献标题:C-14 labelling of NVP RAD001 - A new rapamycin derivative
文献作者:Moenius,T.; et al.
参考来源:J Label Compd Radiopharm 1999,42(1),29
产品链接: CAS No. 159351-69-6››