Cilofungin, L-646991, LY-121019, -Drug Synthesis Database

【结构式】

【药物名称】Cilofungin, L-646991, LY-121019

【化学名称】N-[9beta-[1alpha,2beta-Dihydroxy-2-(4-hydroxyphenyl)ethyl]tetracosahydro-1alpha,13alpha,22alpha,23alpha-tetrahydroxy-6beta,17beta-bis(1beta-hydroxyethyl)-2alpha-methyl-5,8,11,16,19,25-hexaoxo-5H-dipyrrolo[2,1-c:2',1'-l][1,4,7,10,13,16]hexaazacycloheneicosin-20beta-yl]-4-(octyloxy)benzamide
　　　　　　1-[(4R,5R)-4,5-Dihydroxy-N2-[p-(octyloxy)benzoyl]-L-ornithine]echinocandin B
　　　　　　(4R,5R)-4,5-Dihydroxy-N2-[p-(octyloxy)benzoyl]-L-ornithyl-L-threonyl-trans-4-hydroxy-L-prolyl-(S)-4-hydroxy-4-(p-hydroxyphenyl)-L-threonyl-L-threonyl-(3S,4S)-3-hydroxy-4-methyl-L-proline cyclic (6--1)-peptide

【CA登记号】79404-91-4

【分子式】C₄₉H₇₁N₇O₁₇

【分子量】1030.14892

【开发单位】Lilly (Originator)

【药理作用】Antifungal Agents, ANTIINFECTIVE THERAPY, 1,3-beta-Glucan Synthase Inhibitors, Echinocandins

合成路线1

Cilofungin is a semi-synthetic anti-Candida agent that is derived from a three-step process: a) fermentation, isolation and purification of echinocandin B (ECB) (I) using an Aspergillus nidulans strain as the producing culture; b) deacylation of ECB by fermentation using an Actinoplanes utahensis culture to give the ECB nucleus (II); and c) N-acylation of the amino terminus of (II) using an activated ester of 4-octyloxybenzoic acid to give cilofungin.

参考文献中间体

【1】 Molloy, R.M.; Hunt, A.H.; Debono, M.; Fukuda, D.S, Barnhart, M.; Butler, T.F.; Abbott, B.J.; Willard, K.E.; Turner, J.R.; Michel, K.H.; Synthesis of new analogs of echinocandin B by enzymatic deacylation and chemical reacylation of the echinocandin peptide: Synthesis of the antifungal agent cilofungin (LY-121019). J Antibiot 1989, 42, 389.
【2】 Gordee, R.; Debono, M.; CILOFUNGIN < Prop INN; USAN >. Drugs Fut 1989, 14, 10, 939.
【3】 Knusel, F.; Trechler, H.; Voser, W.; Nefeler, R.; Benz, F.; Keller-Schierlein, W.; Nuesch, J.; Echinocandin B. Ein Neuartiges Polypeptide-antibioticum aus Aspergillus nidulans var echinulatus: Isoleirung and Bausteine. Helv Chim Acta 1974, 57, 2459.
【4】 Abbott, B.J.; Gordee, R.S.; Hunt, A.H.; Zeckner, D.J.; Howard, L.C.; Butler, T.F.; Molloy, R.M.; Debono, M.; Barnhart, M.; Turner, J.R.; Willard, K.E.; Fukuda, D.S.; Synthesis and evaluation of LY-121019, a member of a series of semisynthetic analogues of the antifungal lipopeptide echinocandin B. Ann NY Acad Sci 1988, 152.

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)	21343	(2R,6S,9S,11R,12R,14aS,15S,16S,20S,23S,25aS)-23-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-2,11,12,15-tetrahydroxy-6,20-bis[(1R)-1-hydroxyethyl]-16-methyl-9-[[(9E,12E)-9,12-octadecadienoyloxy]amino]hexadecahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosine-5,8,14,19,22,25(9H,25aH)-hexone		C₅₂H₈₁N₇O₁₇	详情	详情
(II)	16118	(2R,6S,9S,11R,12R,14aS,15S,16S,20S,23S,25aS)-9-amino-23-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-2,11,12,15-tetrahydroxy-6,20-bis[(1R)-1-hydroxyethyl]-16-methylhexadecahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosine-5,8,14,19,22,25(9H,25aH)-hexone		C₃₄H₅₁N₇O₁₅	详情	详情

Extended Information