(1R,2R,4S)-4-{(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-二羟基-19,30-二甲氧基-15,17,21,23,29,35-六甲基-2,3,10,14,20-五氧代-11,36-二氧杂-4-氮杂三环[30.3.1.04,9]三十六碳-16,24,26,28-四烯-12-基]丙基}-2-甲氧基环己基2,2,5-三甲基-1,3-二恶烷-5-羧酸酯合成路线 （共 6 条）
→
162635-03-2(1R,2R,4S)-4-{(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-二羟基-19,30-二甲氧基-15,17,21,23,29,35-六甲基-2,3,10,14,20-五氧代-11,36-二氧杂-4-氮杂三环[30.3.1.04,9]三十六碳-16,24,26,28-四烯-12-基]丙基}-2-甲氧基环己基2,2,5-三甲基-1,3-二恶烷-5-羧酸酯
反应条件
1: 2,2-bis(hydroxymethyl)propionic acid isopropylidene ketal With 2,4,6-trichlorobenzoyl chloride; triethylamine in tetrahydrofuran T=0 - 20°C; 5 h; 2: [14C]-Rapamycin With 4-(N,N-dimethlyamino)pyridine in benzene T=20°C;
参考文献
Wyeth
Patent: EP1266899 A2, 2002 ;
Location in patent: Example 10 ;
→
162635-03-2(1R,2R,4S)-4-{(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-二羟基-19,30-二甲氧基-15,17,21,23,29,35-六甲基-2,3,10,14,20-五氧代-11,36-二氧杂-4-氮杂三环[30.3.1.04,9]三十六碳-16,24,26,28-四烯-12-基]丙基}-2-甲氧基环己基2,2,5-三甲基-1,3-二恶烷-5-羧酸酯
反应条件
pyridine in dichloromethane T=5°C; 24 h; Product distribution / selectivity;
参考文献
SANDOZ AG; FELZMANN, Wolfgang; SCHOeNE, Niklas
Patent: WO2012/131019 A1, 2012 ;
Location in patent: Page/Page column 8-9 ;
→
162635-03-2(1R,2R,4S)-4-{(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-二羟基-19,30-二甲氧基-15,17,21,23,29,35-六甲基-2,3,10,14,20-五氧代-11,36-二氧杂-4-氮杂三环[30.3.1.04,9]三十六碳-16,24,26,28-四烯-12-基]丙基}-2-甲氧基环己基2,2,5-三甲基-1,3-二恶烷-5-羧酸酯
反应条件
1: 80 percent / LiCl / PdCl2 / 16 h / Heating 2: Amano II Burkholderia cepacia lipase PS-C; molecular sieves 5 Angstroem / various solvent(s) / 48 h / 42 - 43 °C View Scheme
参考文献
Organic Letters, , vol. 7, # 18 p. 3945 - 3948
→
162635-03-2(1R,2R,4S)-4-{(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-二羟基-19,30-二甲氧基-15,17,21,23,29,35-六甲基-2,3,10,14,20-五氧代-11,36-二氧杂-4-氮杂三环[30.3.1.04,9]三十六碳-16,24,26,28-四烯-12-基]丙基}-2-甲氧基环己基2,2,5-三甲基-1,3-二恶烷-5-羧酸酯
反应条件
5A molecular sieve; Amano II Burkholderia cepacia lipase PS-C in various solvent(s) T=42 - 43°C; 48 h;
参考文献
Organic Letters, , vol. 7, # 18 p. 3945 - 3948
→
162635-03-2(1R,2R,4S)-4-{(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-二羟基-19,30-二甲氧基-15,17,21,23,29,35-六甲基-2,3,10,14,20-五氧代-11,36-二氧杂-4-氮杂三环[30.3.1.04,9]三十六碳-16,24,26,28-四烯-12-基]丙基}-2-甲氧基环己基2,2,5-三甲基-1,3-二恶烷-5-羧酸酯
反应条件
4-(N,N-dimethlyamino)pyridine; triethylamine in dichloromethane T=5°C; Product distribution / selectivity;
参考文献
WO2012/131019 A1, ;
Page/Page column 7-8 ;
162635-03-2(1R,2R,4S)-4-{(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-二羟基-19,30-二甲氧基-15,17,21,23,29,35-六甲基-2,3,10,14,20-五氧代-11,36-二氧杂-4-氮杂三环[30.3.1.04,9]三十六碳-16,24,26,28-四烯-12-基]丙基}-2-甲氧基环己基2,2,5-三甲基-1,3-二恶烷-5-羧酸酯
→
反应条件
sulfuric acid in tetrahydrofuran; water T=0 - 5°C; 48 h;
参考文献
Gu, Jianxin; Ruppen, Mark E.; Cai, Ping
Organic Letters, 2005 , vol. 7, # 18 p. 3945 - 3948
