LY-267108, -Drug Synthesis Database

【结构式】

【药物名称】LY-267108

【化学名称】3(S)-(2,6-Dideoxy-3-C,3-O-dimethyl-alpha-L-altropyranosyloxy)-11(R)-[1(R),2(R)-dihydroxy-1-methylbutyl]-6(R),9-epoxy-2(R),4(S),6,8,10(R)-pentamethyl-5(R)-[3,4,6-trideoxy-3-(dimethylamino)-beta-D-glucopyranosyloxy]-8-undecenolide
　　　　　　[2R-[2R*,3R*(1R*,2R*),6R*,7S*,8S*,9R*,10R*]]-7-[(2,6-Dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribo-hexopyranosyl)oxy]-3-(1,2-dihydroxy-1-methylbutyl)-2,6,8,10,12-pentamethyl-9-[[3,4,6-trideoxy-3-(dimethylamino)-beta-D-xylo-hexopyranosyl]oxy]-4,13-dioxabicyclo[8.2.1]tridec-12-en-5-one

【CA登记号】105882-69-7

【分子式】C₃₇H₆₅NO₁₂

【分子量】715.9301

【开发单位】Lilly (Originator)

【药理作用】Gastric Emptying Disorders,Treatment of of, GASTROINTESTINAL DRUGS, Prokinetic Agents

合成路线1

Intramolecular cyclization of erythromycin A (I) under acidic conditions yields its 8,9-anhydro-6,9-hemiketal derivative (II). Subsequent intramolecular trans-lactonization of (II) under basic conditions produces the ring-contracted compound, LY267108. It has also been synthesized from erythromycin in a single step by heating the latter in a 3:1 mixture of pyridine and acetic acid.

参考文献中间体

【1】 Kurath, P.; Egan, R.S.; Jones, P.H.; Perun, T.J.; Acid degradation of erythromycin A and erythromycin B. Experientia 1971, 27, 4, 362.
【2】 Kibwage, I.O.; Janssen, G.; Verbist, L.; Hoogmartens, J.; Busson, R.; Vanderhaeghe, H.; Identification of novel erythromycin derivatives in mother liquor concentrates of Streptomyces erythraeus. J Antibiot 1987, 40, 1, 1-6.
【3】 Kirst, H.A.; Greenwood, B.; Gidda, J.S.; LY267108. Drugs Fut 1992, 17, 1, 18.
【4】 Kirst, H.A.; Wind, J.A.; Paschal, J.W.; Synthesis of ring-contracted derivatives of erythromycin. J Org Chem 1987, 52, 19, 4359-62.
【5】 Janssen, G.; Hoogmartens, J.; Kibwage, I.O.; Vanderhaeghe, H.; Bracke, J.; Busson, R.; Translactonization in erythromycins. J Org Chem 1987, 52, 6, 990-6.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	33087	(3R,4R,5R,6R,7R,9R,11R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-14-ethyl-7,12,13-trihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3,5,7,9,11,13-hexamethyl-2,10-oxacyclotetradecanedione; Erythromycin A	114-07-8	C₃₇H₆₇NO₁₃	详情	详情
(II)	13641	(2R,3R,4S,5R,8R,9S,10R,11R,12S)-11-[[(2S,3R,4S,6R)-4-(Dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-5-ethyl-3,4-dihydroxy-9-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-2,4,8,10,12,14-hexamethyl-6,15-dioxabicyclo[10.2.1]pentadec-1(14)-en-7-one		C₃₇H₆₅NO₁₂	详情	详情

Extended Information